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Modulation of Learning and Anxiety by Corticotropin-Releasing Factor (CRF) and Stress: Differential Roles of CRF Receptors 1 and 2
Open accessAbstract
The differential modulation of learning and anxiety by corticotropin-releasing factor (CRF) through CRF receptor subtypes 1 (CRFR1) and 2 (CRFR2) is demonstrated. As learning paradigm, context- and tone-dependent fear conditioning of the mouse was used. Injection of CRF into the dorsal hippocampus before training enhanced learning through CRFR1 as demonstrated by the finding that this effect was prevented by the local injection of the unselective CRFR antagonist astressin, but not by the CRFR2-specific antagonist antisauvagine-30 (anti-Svg-30). In contrast, injection of CRF into the lateral intermediate septum impaired learning through CRFR2, as demonstrated by the ability of antisauvagine-30 to block this effect. When antisauvagine-30 was injected alone into the lateral intermediate septum, learning was enhanced. Such tonic control of learning was not observed when astressin or antisauvagine-30 was injected into the dorsal hippocampus. Injection of CRF after the training into the dorsal hippocampus and the lateral intermediate septum also enhanced and impaired learning, respectively. Thus, it was indicated that CRF acted on memory consolidation. It was concluded that the observed effects reflected changes of associative learning and not arousal, attention, or motivation. Although a dose of 20 pmol human/rat CRF was sufficient to affect learning significantly, a fivefold higher dose was required to induce anxiety by injection into the septum. Immobilization for 1 hr generated a stress response that included the induction of anxiety through septal CRFR2 and the subsequent enhancement of learning through hippocampal CRFR1. The involvement of either receptor subtype was demonstrated by region-specific injections of astressin and antisauvagine-30.
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Written from the paper’s full text.
TL;DR
In male BALB/c mice, hippocampal CRF receptor 1 (CRFR1) enhanced fear conditioning, whereas septal CRFR2 impaired it and mediated CRF-induced anxiety. Immobilization stress reproduced these effects sequentially: septal CRFR2-mediated anxiety at 30 min and hippocampal CRFR1-mediated enhancement of fear learning at 3 hr.
Key findings
- Intrahippocampal h/rCRF enhanced context- and tone-dependent fear conditioning; this was blocked by the nonselective CRFR antagonist astressin but not by the CRFR2-selective antagonist antisauvagine-30 (anti-Svg-30), implicating CRFR1. Intra-septal h/rCRF impaired conditioning; this was blocked by both astressin and anti-Svg-30, implicating CRFR2.
- Antagonists alone injected into the lateral intermediate septum enhanced fear conditioning to context and tone, suggesting tonic impairment of learning through septal CRFR2; hippocampal antagonist injections alone had no effect.
- A dose of 20 pmol h/rCRF was sufficient to affect learning, whereas a fivefold higher dose was required to induce anxiety after septal injection. Septal h/rCRF at 500 ng per mouse reduced open-arm time and entries in the elevated plus-maze, and this was antagonized by astressin and anti-Svg-30.
- One-hour immobilization stress increased anxiety at 30 min via septal CRFR2 and enhanced fear conditioning at 3 hr via hippocampal CRFR1; astressin injected into the hippocampus prevented the stress-induced enhancement of conditioned fear, and septal astressin or anti-Svg-30 prevented stress-induced anxiety.
Methods
- Nine-week-old male BALB/c mice were implanted with bilateral cannulae into the lateral ventricles, dorsal hippocampus, or lateral intermediate septum; cannula placement was verified histologically, and only correctly placed mice were analyzed (7–13 mice per group).
- Context- and tone-dependent fear conditioning used a 3 min context, 30 sec 10 kHz tone, and 2 sec 0.7 mA footshock; freezing was scored 24 hr later as the fear index. Anxiety was assessed with the elevated plus-maze, and stress was 1 hr immobilization.
- Peptides included h/rCRF, rat urocortin, ovine CRF, h/rCRF(6–33), astressin, and anti-Svg-30; effects were analyzed with ANOVA followed by Bonferroni-Dunn tests.
Limitations
- The paper states that it is not clear whether the anxiety response is necessary for the subsequent enhancement of learning or whether these responses occur independently. It also notes that in vivo interactions of h/rCRF and urocortin with their receptors differed from in vitro findings, possibly due to partial agonism of rat urocortin toward CRFR1.
- Evident from the text: the study used only male BALB/c mice and a single immobilization stressor, so generality across sex, strain, and stress type is not established. CRFR1 mediation was inferred from blockade by nonselective astressin and lack of blockade by CRFR2-selective anti-Svg-30, rather than by a CRFR1-selective antagonist.
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A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Injection of CRF into the dorsal hippocampus before training enhanced learning through CRFR1 as demonstrated by the finding that this effect was prevented by the local injection of the unselective CRFR antagonist astressin, but not by the CRFR2-specific antagonist antisauvagine-30 (anti-Svg-30).”
- Also stated in: § Modulation of fear conditioning by h/rCRF is restricted to a small time window · plain
“The enhancement of fear conditioning after i.h.injection of h/rCRF was completely blocked by previous administration of astressin but not antisauvagine-30 (anti-Svg-30) (Fig. 6a)”
- Also stated in: § CRF enhances fear conditioning through CRFR1 and impairs it through CRFR2 · plain
“Because the enhancement of fear conditioning by i.h.injection of h /rCRF was prevented by astressin but not anti-Svg-30, it was concluded that this effect was mediated by CRFR1.”
boosteddirect- Asserted: passes — The authors put it forward as true.
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- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- The authors state this as an assumption: The hippocampus and lateral intermediate septum play an important role in associative learning.
- Also stated in: § Modulation of fear conditioning by h/rCRF is restricted to a small time window · plain
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Such tonic control of learning was not observed when astressin or antisauvagine-30 was injected into the dorsal hippocampus.”
- Also stated in: § Modulation of fear conditioning by h/rCRF is restricted to a small time window · plain
“Administration of the CRF receptor antagonists astressin and anti-Svg-30 alone into the hippocampus did not affect fear conditioning”
plain- Asserted: passes — The authors put it forward as true.
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- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- The authors state this as an assumption: The hippocampus and lateral intermediate septum play an important role in associative learning.
- Also stated in: § Modulation of fear conditioning by h/rCRF is restricted to a small time window · plain
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“In contrast, injection of CRF into the lateral intermediate septum impaired learning through CRFR2, as demonstrated by the ability of antisauvagine-30 to block this effect.”
- Also stated in: § Modulation of fear conditioning by h/rCRF is restricted to a small time window · plain
“Both astressin and anti-Svg-30 blocked the memory-impairing effects of i.s.injection of h/rCRF (Fig. 6b).”
- Also stated in: § CRF enhances fear conditioning through CRFR1 and impairs it through CRFR2 · hedged
“In contrast, the impairment of fear conditioning observed after i.s.application of h /rCRF was mediated by CRFR2, as indicated by the ability of both astressin and anti-Svg-30 to block this effect.”
boosteddirect- Asserted: passes — The authors put it forward as true.
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- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- The authors state this as an assumption: The hippocampus and lateral intermediate septum play an important role in associative learning.
- Also stated in: § Modulation of fear conditioning by h/rCRF is restricted to a small time window · plain
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“When antisauvagine-30 was injected alone into the lateral intermediate septum, learning was enhanced.”
- Also stated in: § Modulation of fear conditioning by h/rCRF is restricted to a small time window · plain
“Administration of the CRF receptor antagonists astressin and anti-Svg-30 alone into the hippocampus did not affect fear conditioning, whereas their i.s.injection significantly enhanced fear conditioning to context (F (5,42) ϭ 12.089, p Ͻ 0.001) and tone (F (5,42) ϭ 11.664, p Ͻ 0.001).”
plaindirect- Asserted: passes — The authors put it forward as true.
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- Load-bearing: passes — The paper’s conclusions depend on it.
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- The authors state this as an assumption: The hippocampus and lateral intermediate septum play an important role in associative learning.
- Also stated in: § Modulation of fear conditioning by h/rCRF is restricted to a small time window · plain
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The strongest effect was observed after intracerebroventricular injection of h/rCRF.”
§ Modulation of Learning and Anxiety by Corticotropin-Releasing Factor (CRF) and Stress: Differential Roles of CRF Receptors 1 and 2 > CRF-like peptides modulate fear conditioning in a brain region-specific manner
boosteddirect- Asserted: passes — The authors put it forward as true.
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A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Statistical analysis (twoway ANOVA followed by the Bonferonni-Dunn test) revealed that h/r CRF, h/r CRF (6 -33), rUcn, and oCRF dosedependently enhanced fear conditioning to both context, F (12,103) ϭ 5.158, p Ͻ 0.001 (Fig. 1a) and tone, F (12,103) ϭ 5.365, p Ͻ 0.001 (Fig. 2b).”
§ Modulation of Learning and Anxiety by Corticotropin-Releasing Factor (CRF) and Stress: Differential Roles of CRF Receptors 1 and 2 > CRF-like peptides modulate fear conditioning in a brain region-specific manner
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“Injection of CRF-like peptides into the parietal somatosensory cortex and striatum, brain regions adjacent to the hippocampus and septum, respectively, did not produce any significant effects on contextand tone-dependent fear conditioning (Fig. 3c,d).”
§ Modulation of Learning and Anxiety by Corticotropin-Releasing Factor (CRF) and Stress: Differential Roles of CRF Receptors 1 and 2 > CRF-like peptides modulate fear conditioning in a brain region-specific manner
plain- Asserted: passes — The authors put it forward as true.
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A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“whereas oCRF and h /r CRF(6 -33) did not affect fear conditioning after i.s.injection.”
§ Modulation of Learning and Anxiety by Corticotropin-Releasing Factor (CRF) and Stress: Differential Roles of CRF Receptors 1 and 2 > CRF-like peptides modulate fear conditioning in a brain region-specific manner
plain- Asserted: passes — The authors put it forward as true.
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In the paper
“The lowest doses of CRF-like peptides per mouse that produced significant enhancement of conditioning to context and tone were 100 ng (20 pmol) h/rCRF, 200 ng (40 pmol) rUcn, 200 ng (40 pmol) oCRF, and 200 ng(60 pmol) h/rCRF (6 -33).”
§ Modulation of Learning and Anxiety by Corticotropin-Releasing Factor (CRF) and Stress: Differential Roles of CRF Receptors 1 and 2 > CRF-like peptides modulate fear conditioning in a brain region-specific manner
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“h /rCRF was more effective than Ucn in modulating fear conditioning, whereas oCRF and h /r CRF(6 -33) did not affect fear conditioning after i.s.injection.”
§ Modulation of Learning and Anxiety by Corticotropin-Releasing Factor (CRF) and Stress: Differential Roles of CRF Receptors 1 and 2 > CRF-like peptides modulate fear conditioning in a brain region-specific manner
plaindirect- Asserted: passes — The authors put it forward as true.
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A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Similarly, all CRF-like peptides enhanced acquisition of context-dependent (F (4,32) ϭ 10.795, p Ͻ 0.001) and tone-dependent fear (F (4,32) ϭ 9.881, p Ͻ 0.001) (Fig. 3a), after intrahippocampal (i.h.) injection.”
§ Modulation of Learning and Anxiety by Corticotropin-Releasing Factor (CRF) and Stress: Differential Roles of CRF Receptors 1 and 2 > CRF-like peptides modulate fear conditioning in a brain region-specific manner
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- The authors state this as an assumption: The hippocampus and lateral intermediate septum play an important role in associative learning.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“In contrast, injection of h /rCRF or Ucn into the lateral intermediate septum (i.s.) significantly impaired context-dependent (F (4,32) ϭ 15.388, p Ͻ 0.001) and tone-dependent fear conditioning (F (4,32) ϭ 14.256, p Ͻ 0.001) (Fig. 3b).”
§ Modulation of Learning and Anxiety by Corticotropin-Releasing Factor (CRF) and Stress: Differential Roles of CRF Receptors 1 and 2 > CRF-like peptides modulate fear conditioning in a brain region-specific manner
plaindirect- Asserted: passes — The authors put it forward as true.
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- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- The authors state this as an assumption: The hippocampus and lateral intermediate septum play an important role in associative learning.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“One hour immobilization produced anxious behavior when applied 30 min before the elevated plus-maze test (Fig. 9a,b), as revealed by reduced time spent and number of entries on the open arms of the maze (F (3,37) ϭ 6.323, p Ͻ 0.01).”
§ Modulation of Learning and Anxiety by Corticotropin-Releasing Factor (CRF) and Stress: Differential Roles of CRF Receptors 1 and 2 > h/rCRF mediates stress-induced enhancement of fear conditioning through hippocampal CRFR1 and stressinduced anxiety through septal CRFR2
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“In mice subjected to 1 hr immobilization stress, fear conditioning to context ((F 3,40 ϭ 7.134, p Ͻ 0.01) and tone (F 3,40 ϭ 6.795, p Ͻ 0.01) was significantly increased 3 hr after termination of the stress when compared with nonstressed controls (Fig. 8a).”
§ Modulation of Learning and Anxiety by Corticotropin-Releasing Factor (CRF) and Stress: Differential Roles of CRF Receptors 1 and 2 > h/rCRF mediates stress-induced enhancement of fear conditioning through hippocampal CRFR1 and stressinduced anxiety through septal CRFR2
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“The dose required to produce a maximal effect after i.h.injection (to 100% of values observed in mice injected with aCSF alone, in the absence of peptide) was 50 ng h/rCRF per injection site (Fig. 4a,b).”
§ Modulation of Learning and Anxiety by Corticotropin-Releasing Factor (CRF) and Stress: Differential Roles of CRF Receptors 1 and 2 > Region-specific modulation of fear conditioning by h/ rCRF is dose dependent
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“Both astressin and anti-Svg-30 blocked the memory-impairing effects of i.s.injection of h/rCRF (Fig. 6b).”
§ Modulation of Learning and Anxiety by Corticotropin-Releasing Factor (CRF) and Stress: Differential Roles of CRF Receptors 1 and 2 > Modulation of fear conditioning by h/rCRF is restricted to a small time window
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“Context-dependent fear was impaired by i.s.injection of h/rCRF before and immediately after the training, whereas injection 1 hr after the training was ineffective.”
§ Modulation of Learning and Anxiety by Corticotropin-Releasing Factor (CRF) and Stress: Differential Roles of CRF Receptors 1 and 2 > Modulation of fear conditioning by h/rCRF is restricted to a small time window
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
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- The authors state this as an assumption: The hippocampus and lateral intermediate septum play an important role in associative learning.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Astressin completely antagonized stress-induced enhancement of conditioned fear when given by i.h.injection either before the immobilization stress or before the training (Fig. 8b).”
§ Modulation of Learning and Anxiety by Corticotropin-Releasing Factor (CRF) and Stress: Differential Roles of CRF Receptors 1 and 2 > h/rCRF mediates stress-induced enhancement of fear conditioning through hippocampal CRFR1 and stressinduced anxiety through septal CRFR2
plaindirect- Asserted: passes — The authors put it forward as true.
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- The authors state this as an assumption: The hippocampus and lateral intermediate septum play an important role in associative learning.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“In addition to the effects observed previously when h/rCRF was injected before the training, i.h.administration of h/rCRF immediately after the training also enhanced acquisition of context-dependent (F (5,48) ϭ 9.568, p Ͻ 0.001) and tonedependent fear (F (5,48) ϭ 9.344, p Ͻ 0.001) (Fig. 5a).”
§ Modulation of Learning and Anxiety by Corticotropin-Releasing Factor (CRF) and Stress: Differential Roles of CRF Receptors 1 and 2 > Modulation of fear conditioning by h/rCRF is restricted to a small time window
plaindirect- Asserted: passes — The authors put it forward as true.
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- The authors state this as an assumption: The hippocampus and lateral intermediate septum play an important role in associative learning.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“An h/rCRF i.h.injection 1 hr after training did not exhibit any significant effect.”
§ Modulation of Learning and Anxiety by Corticotropin-Releasing Factor (CRF) and Stress: Differential Roles of CRF Receptors 1 and 2 > Modulation of fear conditioning by h/rCRF is restricted to a small time window
plain- Asserted: passes — The authors put it forward as true.
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In the paper
“An i.s.injection of h/rCRF differentially affected acquisition of context-dependent (F (5,46) ϭ 9.133, p Ͻ 0.001) and tonedependent fear conditioning (F (5,46) ϭ 7.95, p Ͻ 0.001) (Fig. 5b).”
§ Modulation of Learning and Anxiety by Corticotropin-Releasing Factor (CRF) and Stress: Differential Roles of CRF Receptors 1 and 2 > Modulation of fear conditioning by h/rCRF is restricted to a small time window
plaindirect- Asserted: passes — The authors put it forward as true.
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- The authors state this as an assumption: The hippocampus and lateral intermediate septum play an important role in associative learning.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Tone-dependent fear was impaired only when i.s.injection of h/rCRF was given before the training.”
§ Modulation of Learning and Anxiety by Corticotropin-Releasing Factor (CRF) and Stress: Differential Roles of CRF Receptors 1 and 2 > Modulation of fear conditioning by h/rCRF is restricted to a small time window
plaindirect- Asserted: passes — The authors put it forward as true.
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- The authors state this as an assumption: The hippocampus and lateral intermediate septum play an important role in associative learning.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The dose of h /rCRF modulating fear conditioning did not affect plus-maze behavior (Fig. 7), as evaluated by time spent, number of entries, and distance crossed on the open and closed arms of an elevated plus-maze.”
§ Modulation of Learning and Anxiety by Corticotropin-Releasing Factor (CRF) and Stress: Differential Roles of CRF Receptors 1 and 2 > h/rCRF induces anxious behavior through septal CRFR2 but not hippocampal CRFR1
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In the paper
“The same dose applied intracerebroventricularly produced an enhancement of 55% of control values (Fig. 2a,b).”
§ Modulation of Learning and Anxiety by Corticotropin-Releasing Factor (CRF) and Stress: Differential Roles of CRF Receptors 1 and 2 > Region-specific modulation of fear conditioning by h/ rCRF is dose dependent
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“This finding was consistent with the tonic role of septal CRFR2, as demonstrated by the ability of the CRFR antagonists astressin and anti-Svg-30 to produce an opposite effect when compared with h/rCRF.”
§ Modulation of Learning and Anxiety by Corticotropin-Releasing Factor (CRF) and Stress: Differential Roles of CRF Receptors 1 and 2 > The effects of CRF on fear conditioning are specific for memory consolidation
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In the paper
“After post-training i.s.injections of h/rCRF, a dissociation of CRFR2-mediated effects on context and tone was observed.”
§ Modulation of Learning and Anxiety by Corticotropin-Releasing Factor (CRF) and Stress: Differential Roles of CRF Receptors 1 and 2 > The effects of CRF on fear conditioning are specific for memory consolidation
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“Modulation of conditioned fear observed in the present experiments was specific for learning and not performance, as demonstrated by the efficiency of h/rCRF to modulate the acquisition of the fear response when injected immediately after the training, but not at a later time point.”
§ Modulation of Learning and Anxiety by Corticotropin-Releasing Factor (CRF) and Stress: Differential Roles of CRF Receptors 1 and 2 > The effects of CRF on fear conditioning are specific for memory consolidation
boosteddirect- Asserted: passes — The authors put it forward as true.
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In the paper
“The inefficiency of CRFR antagonists alone to affect the behavior of mice in the plus-maze suggested that hippocampal and septal CRFR did not contribute to a significant extent to the tonic regulation of anxiety by CRF.”
§ Modulation of Learning and Anxiety by Corticotropin-Releasing Factor (CRF) and Stress: Differential Roles of CRF Receptors 1 and 2 > Septal CRFR2 mediates CRF-induced anxiety
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In the paper
“In agreement with previous findings (Behan et al., 1995), the dose of h/rCRF required for induction of anxiety-related behavior was higher than the dose that modulated learning.”
§ Modulation of Learning and Anxiety by Corticotropin-Releasing Factor (CRF) and Stress: Differential Roles of CRF Receptors 1 and 2 > Septal CRFR2 mediates CRF-induced anxiety
What the sources say
- Not checked yetcites Behan et al., 1995
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- Based: passes — The paper gives a reason why it holds.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The dose of h/rCRF required to produce maximal enhancement or impairment of fear conditioning did not affect anxiety.”
§ Modulation of Learning and Anxiety by Corticotropin-Releasing Factor (CRF) and Stress: Differential Roles of CRF Receptors 1 and 2 > Septal CRFR2 mediates CRF-induced anxiety
plain- Asserted: passes — The authors put it forward as true.
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- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Stress-induced anxious behavior was fully prevented by i.s.injection of anti-Svg-30.”
§ Modulation of Learning and Anxiety by Corticotropin-Releasing Factor (CRF) and Stress: Differential Roles of CRF Receptors 1 and 2 > Septal CRFR2 mediates CRF-induced anxiety
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The stress-induced increase of anxiety and fear conditioning could be fully prevented by septal and hippocampal CRFR antagonists, respectively, which under nonstress conditions did not affect either behavior by themselves.”
§ Modulation of Learning and Anxiety by Corticotropin-Releasing Factor (CRF) and Stress: Differential Roles of CRF Receptors 1 and 2 > Septal CRFR2 mediates stress-induced anxiety, whereas hippocampal CRFR1 mediates stress-induced enhancement of fear conditioning
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Interestingly, astressin prevented the effects of stress when given by i.h.application before as well as 3 hr after immobilization, suggesting that hippocampal CRFR1 was activated biphasically, during stress and 3 hr after termination of the stressful stimulus.”
§ Modulation of Learning and Anxiety by Corticotropin-Releasing Factor (CRF) and Stress: Differential Roles of CRF Receptors 1 and 2 > Septal CRFR2 mediates stress-induced anxiety, whereas hippocampal CRFR1 mediates stress-induced enhancement of fear conditioning
hedgeddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Thus, it was indicated that CRF acted on memory consolidation.”
hedgeddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
None of the sources cited for this claim have been checked yet.
In the paper
“Modulation of learning and memory seems to be one of the major roles of CRF in rodent and human brain.”
§ Modulation of Learning and Anxiety by Corticotropin-Releasing Factor (CRF) and Stress: Differential Roles of CRF Receptors 1 and 2 > Key words: CRF receptor 1; CRF receptor 2; fear conditioning; anxiety; stress; hippocampus; lateral septum
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“Increasing evidence suggests that these effects are independent of the arousal state, as indicated by the observation that CRF modulates learning and memory at a low dose that does not affect arousal, locomotion, or anxiety (Behan et al., 1995).”
§ Modulation of Learning and Anxiety by Corticotropin-Releasing Factor (CRF) and Stress: Differential Roles of CRF Receptors 1 and 2 > Key words: CRF receptor 1; CRF receptor 2; fear conditioning; anxiety; stress; hippocampus; lateral septum
What the sources say
- Not checked yetcites Behan et al., 1995
hedgeddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
None of the sources cited for this claim have been checked yet.
In the paper
“Intracerebroventricular injections of CRF or its displacement from CRF-BP before or immediately after training enhances memory in multiple learning tasks (Koob and Bloom, 1985;Liang and Lee, 1988;Behan et al., 1995, Heinrichs et al., 1997), whereas intracerebroventricular administration before the memory test seems to impair memory (Diamant and De Wied, 1993).”
§ Modulation of Learning and Anxiety by Corticotropin-Releasing Factor (CRF) and Stress: Differential Roles of CRF Receptors 1 and 2 > Key words: CRF receptor 1; CRF receptor 2; fear conditioning; anxiety; stress; hippocampus; lateral septum
What the sources say
- Not checked yetcites Koob and Bloom, 1985
- Not checked yetcites Liang and Lee, 1988
- Not checked yetcites Behan et al., 1995
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
None of the sources cited for this claim have been checked yet.
In the paper
“indicating that enhanced freezing was not caused by effects of h /rCRF on locomotor activity (Sutton et al., 1982) or place aversion (C ador et al., 1992).”
§ Modulation of Learning and Anxiety by Corticotropin-Releasing Factor (CRF) and Stress: Differential Roles of CRF Receptors 1 and 2 > CRF-like peptides modulate fear conditioning in a brain region-specific manner
What the sources say
- Not checked yetcites Sutton et al., 1982
- Not checked yetcites Cador et al., 1992
hedged- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
None of the sources cited for this claim have been checked yet.
In the paper
“Decreased time on the open arms and decreased number of open arm entries are believed to reflect anxious behavior (Dunn and Berridge, 1990;De Souza, 1995).”
§ Modulation of Learning and Anxiety by Corticotropin-Releasing Factor (CRF) and Stress: Differential Roles of CRF Receptors 1 and 2 > h/rCRF induces anxious behavior through septal CRFR2 but not hippocampal CRFR1
What the sources say
- Not checked yetcites Dunn and Berridge, 1990
- Not checked yetcites De Souza, 1995
hedgedcorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“In contrast to astressin, a nonselective antagonist for both CRFR1 and 2, anti-Svg-30 was demonstrated to block preferentially CRFR2 (Ru ¨hmann et al., 1998).”
§ Modulation of Learning and Anxiety by Corticotropin-Releasing Factor (CRF) and Stress: Differential Roles of CRF Receptors 1 and 2 > Modulation of fear conditioning by h/rCRF is restricted to a small time window
What the sources say
- Not checked yetcites Rühmann et al., 1998
boosteddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“These results excluded the possibility that the effects observed after i.h.injection of h/rCRF were caused by peptide leakage into the lateral brain ventricles.”
§ Modulation of Learning and Anxiety by Corticotropin-Releasing Factor (CRF) and Stress: Differential Roles of CRF Receptors 1 and 2 > Region-specific modulation of fear conditioning by h/ rCRF is dose dependent
boosted- Asserted: passes — The authors put it forward as true.
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- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The receptor specificity of the CRF effects on fear conditioning was demonstrated for the first time in the present study by using two CRFR antagonists: the nonselective antagonist astressin and the selective CRFR2 antagonist anti-Svg-30.”
§ Modulation of Learning and Anxiety by Corticotropin-Releasing Factor (CRF) and Stress: Differential Roles of CRF Receptors 1 and 2 > CRF enhances fear conditioning through CRFR1 and impairs it through CRFR2
boosteddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“In view of the inability of h/rCRF to impair conditioning to tone, it was suggested that stimulation of CRFR2 had to occur before or during training to affect tone-dependent fear conditioning.”
§ Modulation of Learning and Anxiety by Corticotropin-Releasing Factor (CRF) and Stress: Differential Roles of CRF Receptors 1 and 2 > The effects of CRF on fear conditioning are specific for memory consolidation
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Thus, it appears that the in vivo interactions of h/rCRF and Ucn with their receptors differed from the ones in vitro.”
§ Modulation of Learning and Anxiety by Corticotropin-Releasing Factor (CRF) and Stress: Differential Roles of CRF Receptors 1 and 2 > DISCUSSION CRF-like peptides modulate fear conditioning in a region-specific manner
hedgedcorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- The authors state this as an assumption: Ucn may be the putative ligand for CRFR2.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Modulation of conditioned fear observed in the present experiments was specific for learning and not performance, as demonstrated by the efficiency of h/rCRF to modulate the acquisition of the fear response when injected immediately after the training, but not at a later time point.”
§ Modulation of Learning and Anxiety by Corticotropin-Releasing Factor (CRF) and Stress: Differential Roles of CRF Receptors 1 and 2 > The effects of CRF on fear conditioning are specific for memory consolidation
boosteddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The results of the i.h.injections demonstrated that this effect was mediated by the dorsal hippocampus.”
§ Modulation of Learning and Anxiety by Corticotropin-Releasing Factor (CRF) and Stress: Differential Roles of CRF Receptors 1 and 2 > DISCUSSION CRF-like peptides modulate fear conditioning in a region-specific manner
boosteddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- The authors state this as an assumption: The hippocampus and lateral intermediate septum play an important role in associative learning.
None of the sources cited for this claim have been checked yet.
In the paper
“The impairment of contextual fear conditioning by i.s.injection of h/rCRF after the training was probably the result of longer processing of contextual stimuli (Rudy and Morledge, 1994; O. Stiedl and J. Spiess, unpublished observations), which may render this form of conditioning susceptible to modulation over a longer time.”
§ Modulation of Learning and Anxiety by Corticotropin-Releasing Factor (CRF) and Stress: Differential Roles of CRF Receptors 1 and 2 > The effects of CRF on fear conditioning are specific for memory consolidation
What the sources say
- Not checked yetcites Rudy and Morledge, 1994
- Not checked yetcites O. Stiedl and J. Spiess, unpublished observations
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“The ability of anti-Svg-30, originally developed as a CRFR2 antagonist, to prevent the behavioral effect of h/rCRF was consistent with previous data demonstrating that the CRFR2 ␣ and  splice variants share similar ligand-binding properties (Donaldson et al., 1996).”
§ Modulation of Learning and Anxiety by Corticotropin-Releasing Factor (CRF) and Stress: Differential Roles of CRF Receptors 1 and 2 > CRF enhances fear conditioning through CRFR1 and impairs it through CRFR2
What the sources say
- Not checked yetcites Donaldson et al., 1996
boosted- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“Such difference could be explained, at least in part, by the partial agonism of rUcn toward CRFR1 (A.Ru ¨hmann and J. Spiess, unpublished results).”
§ Modulation of Learning and Anxiety by Corticotropin-Releasing Factor (CRF) and Stress: Differential Roles of CRF Receptors 1 and 2 > DISCUSSION CRF-like peptides modulate fear conditioning in a region-specific manner
What the sources say
- Not checked yetcites A. Rühmann and J. Spiess, unpublished results
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“These results suggested that impairment of fear conditioning by h/rCRF through the lateral septal area may be mediated by the recently identified CRFR2.”
§ Modulation of Learning and Anxiety by Corticotropin-Releasing Factor (CRF) and Stress: Differential Roles of CRF Receptors 1 and 2 > DISCUSSION CRF-like peptides modulate fear conditioning in a region-specific manner
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- The authors state this as an assumption: The hippocampus and lateral intermediate septum play an important role in associative learning.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The results from this study demonstrated that learning of aversive stimuli after classic fear conditioning is profoundly and differentially modulated by the hippocampal CRFR1 and septal CRFR2 systems.”
§ Modulation of Learning and Anxiety by Corticotropin-Releasing Factor (CRF) and Stress: Differential Roles of CRF Receptors 1 and 2 > The effects of CRF on fear conditioning are specific for memory consolidation
boosteddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
None of the sources cited for this claim have been checked yet.
In the paper
“Numerous studies, using lesioning (Kim and Fanselow, 1992;Phillips and LeDoux, 1992) and genetic (Aiba et al., 1994;Tsien et al., 1996) strategies, indicated that the hippocampus plays a crucial role in context-dependent fear conditioning.”
§ Modulation of Learning and Anxiety by Corticotropin-Releasing Factor (CRF) and Stress: Differential Roles of CRF Receptors 1 and 2 > The effects of CRF on fear conditioning are specific for memory consolidation
What the sources say
- Not checked yetcites Kim and Fanselow, 1992
- Not checked yetcites Phillips and LeDoux, 1992
- Not checked yetcites Aiba et al., 1994 source
hedgeddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
None of the sources cited for this claim have been checked yet.
In the paper
“It appears, therefore, that decreased anxious responses recently observed with CRFR1-deficient mice (Smith et al., 1998;Timpl et al., 1998) could be caused by CRFR1 deficiency in brain areas other than the hippocampus.”
§ Modulation of Learning and Anxiety by Corticotropin-Releasing Factor (CRF) and Stress: Differential Roles of CRF Receptors 1 and 2 > Septal CRFR2 mediates CRF-induced anxiety
What the sources say
- Not checked yetcites Smith et al., 1998
- Not checked yetcites Timpl et al., 1998
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Thus, enhancement of context-dependent fear, observed after injection of CRF-like peptides into the CA1 area, was consistent with this view.”
§ Modulation of Learning and Anxiety by Corticotropin-Releasing Factor (CRF) and Stress: Differential Roles of CRF Receptors 1 and 2 > The effects of CRF on fear conditioning are specific for memory consolidation
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Thus, an additional novel role of septal CRFR2 was demonstrated in anxiety generated by pharmacological or stress-induced increase of CRF activity.”
§ Modulation of Learning and Anxiety by Corticotropin-Releasing Factor (CRF) and Stress: Differential Roles of CRF Receptors 1 and 2 > Septal CRFR2 mediates CRF-induced anxiety
boosteddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Rests on an assumption: Immobilization stress increases endogenous CRF activity in the brain areas studied.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The inefficiency of CRFR antagonists alone to affect the behavior of mice in the plus-maze suggested that hippocampal and septal CRFR did not contribute to a significant extent to the tonic regulation of anxiety by CRF.”
§ Modulation of Learning and Anxiety by Corticotropin-Releasing Factor (CRF) and Stress: Differential Roles of CRF Receptors 1 and 2 > Septal CRFR2 mediates CRF-induced anxiety
hedged- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The presented data indicate that the role of the endogenous CRF system in learning and anxiety strongly depends on the brain area, receptor type, and previous stressful experiences.”
§ Modulation of Learning and Anxiety by Corticotropin-Releasing Factor (CRF) and Stress: Differential Roles of CRF Receptors 1 and 2 > Septal CRFR2 mediates stress-induced anxiety, whereas hippocampal CRFR1 mediates stress-induced enhancement of fear conditioning
boostedcorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Rests on an assumption: Immobilization stress increases endogenous CRF activity in the brain areas studied.
In the paper
“These results, demonstrating potentiation of CRFR-mediated effects after stress, are consistent with increasing recent evidence suggesting that the glucocorticoid hormones lower the threshold for CRF actions in the limbic system (Schulkin et al., 1998).”
§ Modulation of Learning and Anxiety by Corticotropin-Releasing Factor (CRF) and Stress: Differential Roles of CRF Receptors 1 and 2 > Septal CRFR2 mediates stress-induced anxiety, whereas hippocampal CRFR1 mediates stress-induced enhancement of fear conditioning
What the sources say
- Not checked yetcites Schulkin et al., 1998
boosteddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Rests on an assumption: Immobilization stress increases endogenous CRF activity in the brain areas studied.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Thus the existence of two receptors mediating opposite effects under different conditions provides the CRF system with a high flexibility and a dynamic role in the plastic adaptation of the C NS to environmental challenge.”
§ Modulation of Learning and Anxiety by Corticotropin-Releasing Factor (CRF) and Stress: Differential Roles of CRF Receptors 1 and 2 > Septal CRFR2 mediates stress-induced anxiety, whereas hippocampal CRFR1 mediates stress-induced enhancement of fear conditioning
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Rests on an assumption: Immobilization stress increases endogenous CRF activity in the brain areas studied.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“However, impairment of learning through septal CRFR2 under baseline conditions and enhancement of learning through hippocampal CRFR1 after stress demonstrated that the brain CRF systems may subserve different roles in the processing of sensory information generated by stimuli of different biological significance.”
§ Modulation of Learning and Anxiety by Corticotropin-Releasing Factor (CRF) and Stress: Differential Roles of CRF Receptors 1 and 2 > Septal CRFR2 mediates stress-induced anxiety, whereas hippocampal CRFR1 mediates stress-induced enhancement of fear conditioning
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Rests on an assumption: Immobilization stress increases endogenous CRF activity in the brain areas studied.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Interestingly, astressin prevented the effects of stress when given by i.h.application before as well as 3 hr after immobilization, suggesting that hippocampal CRFR1 was activated biphasically, during stress and 3 hr after termination of the stressful stimulus.”
§ Modulation of Learning and Anxiety by Corticotropin-Releasing Factor (CRF) and Stress: Differential Roles of CRF Receptors 1 and 2 > Septal CRFR2 mediates stress-induced anxiety, whereas hippocampal CRFR1 mediates stress-induced enhancement of fear conditioning
hedgeddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Rests on an assumption: Immobilization stress increases endogenous CRF activity in the brain areas studied.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The different time course of stress-induced facilitation of anxious behavior and fear conditioning suggests that the CRF actions mediated through septal CRFR2 and hippocampal CRFR1 are differentially affected by stress.”
§ Modulation of Learning and Anxiety by Corticotropin-Releasing Factor (CRF) and Stress: Differential Roles of CRF Receptors 1 and 2 > Septal CRFR2 mediates stress-induced anxiety, whereas hippocampal CRFR1 mediates stress-induced enhancement of fear conditioning
hedgeddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Rests on an assumption: Immobilization stress increases endogenous CRF activity in the brain areas studied.
- It may state two separate claims as one. 27
- Probably not a substantial claim. 5
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Injection of CRF after the training into the dorsal hippocampus and the lateral intermediate septum also enhanced and impaired learning, respectively.”
- Also stated in: § Modulation of fear conditioning by h/rCRF is restricted to a small time window · plain
“i.h.administration of h/rCRF immediately after the training also enhanced acquisition of context-dependent (F (5,48) ϭ 9.568, p Ͻ 0.001) and tonedependent fear (F (5,48) ϭ 9.344, p Ͻ 0.001) (Fig. 5a).”
- Also stated in: § Modulation of fear conditioning by h/rCRF is restricted to a small time window · plain
“Context-dependent fear was impaired by i.s.injection of h/rCRF before and immediately after the training, whereas injection 1 hr after the training was ineffective.”
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- The authors state this as an assumption: The hippocampus and lateral intermediate septum play an important role in associative learning.
- Also stated in: § Modulation of fear conditioning by h/rCRF is restricted to a small time window · plain
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Although a dose of 20 pmol human/rat CRF was sufficient to affect learning significantly, a fivefold higher dose was required to induce anxiety by injection into the septum.”
- Also stated in: § h/rCRF induces anxious behavior through septal CRFR2 but not hippocampal CRFR1 · plain
“The dose of h /rCRF modulating fear conditioning did not affect plus-maze behavior (Fig. 7), as evaluated by time spent, number of entries, and distance crossed on the open and closed arms of an elevated plus-maze.However, i.s.injection of 500 ng h /rCRF per mouse significantly reduced the time spent (F (4,45) ϭ 4.32, p Ͻ 0.01) (Fig. 7a) and the number of entries (F (4,45) ϭ 4.11, p Ͻ 0.01) (Fig.”
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Also stated in: § h/rCRF induces anxious behavior through septal CRFR2 but not hippocampal CRFR1 · plain
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Immobilization for 1 hr generated a stress response that included the induction of anxiety through septal CRFR2 and the subsequent enhancement of learning through hippocampal CRFR1.”
- Also stated in: § h/rCRF mediates stress-induced enhancement of fear conditioning through hippocampal CRFR1 and stressinduced anxiety through septal CRFR2 · plain
“In mice subjected to 1 hr immobilization stress, fear conditioning to context ((F 3,40 ϭ 7.134, p Ͻ 0.01) and tone (F 3,40 ϭ 6.795, p Ͻ 0.01) was significantly increased 3 hr after termination of the stress when compared with nonstressed controls (Fig. 8a).”
- Also stated in: § h/rCRF mediates stress-induced enhancement of fear conditioning through hippocampal CRFR1 and stressinduced anxiety through septal CRFR2 · plain
“Astressin and anti-SVG-30 completely prevented stress-induced anxiety when given by i.s.injection (Fig. 9c,d) but not by i.h.injection (data not shown) before the immobilization stress.”
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- The authors state this as an assumption: The hippocampus and lateral intermediate septum play an important role in associative learning.
- Also stated in: § h/rCRF mediates stress-induced enhancement of fear conditioning through hippocampal CRFR1 and stressinduced anxiety through septal CRFR2 · plain
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Enhancement of freezing by i.h.injection of h/rCRF was demonstrated only for fear-conditioned mice, but not for mice receiving peptide without a shock (Fig. 2a)”
§ Modulation of Learning and Anxiety by Corticotropin-Releasing Factor (CRF) and Stress: Differential Roles of CRF Receptors 1 and 2 > CRF-like peptides modulate fear conditioning in a brain region-specific manner
boosted- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The locomotor activities and the activity burst in response to the shock of mice injected with CRF-like peptides did not differ from the values of control mice injected with aCSF (data not shown).”
§ Modulation of Learning and Anxiety by Corticotropin-Releasing Factor (CRF) and Stress: Differential Roles of CRF Receptors 1 and 2 > CRF-like peptides modulate fear conditioning in a brain region-specific manner
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The minimally required dose for modulation of fear conditioning after local administration of h /rCRF was 25 ng per injection site [a total of 50 ng (10 pmol) per mouse], a dose ineffective after intracerebroventricular injection of h /rCRF.”
§ Modulation of Learning and Anxiety by Corticotropin-Releasing Factor (CRF) and Stress: Differential Roles of CRF Receptors 1 and 2 > Region-specific modulation of fear conditioning by h/ rCRF is dose dependent
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Subsequent experiments demonstrated that i.h.administration of h/rCRF enhanced context-dependent (F (3,35) ϭ 9.726, p Ͻ 0.001) and tone-dependent fear (F (3,35) ϭ 9.456, p Ͻ 0.001) (Fig. 3a), whereas i.s.administration of h/rCRF impaired context-dependent (F (3,31) ϭ 8.120, p Ͻ 0.001) (Fig. 4a) and tone-dependent fear (F (3,31) ϭ 7.724, p Ͻ 0.001) (Fig. 4b) in a dose-dependent manner.”
§ Modulation of Learning and Anxiety by Corticotropin-Releasing Factor (CRF) and Stress: Differential Roles of CRF Receptors 1 and 2 > Region-specific modulation of fear conditioning by h/ rCRF is dose dependent
boosteddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- The authors state this as an assumption: The hippocampus and lateral intermediate septum play an important role in associative learning.
In the paper
“The enhancement of fear conditioning after i.h.injection of h/rCRF was completely blocked by previous administration of astressin but not antisauvagine-30 (anti-Svg-30) (Fig. 6a), a peptidic antagonist recently developed in our laboratory (Ru ¨hmann et al., 1998).”
§ Modulation of Learning and Anxiety by Corticotropin-Releasing Factor (CRF) and Stress: Differential Roles of CRF Receptors 1 and 2 > Modulation of fear conditioning by h/rCRF is restricted to a small time window
What the sources say
- Not checked yetcites Rühmann et al., 1998
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Administration of the CRF receptor antagonists astressin and anti-Svg-30 alone into the hippocampus did not affect fear conditioning, whereas their i.s.injection significantly enhanced fear conditioning to context (F (5,42) ϭ 12.089, p Ͻ 0.001) and tone (F (5,42) ϭ 11.664, p Ͻ 0.001).”
§ Modulation of Learning and Anxiety by Corticotropin-Releasing Factor (CRF) and Stress: Differential Roles of CRF Receptors 1 and 2 > Modulation of fear conditioning by h/rCRF is restricted to a small time window
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- The authors state this as an assumption: The hippocampus and lateral intermediate septum play an important role in associative learning.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Astressin and anti-Svg-30 applied by i.s.injection completely antagonized anxiety induced by i.s.injection of h/rCRF (Fig. 7a,b), without affecting baseline anxiety levels.”
§ Modulation of Learning and Anxiety by Corticotropin-Releasing Factor (CRF) and Stress: Differential Roles of CRF Receptors 1 and 2 > h/rCRF induces anxious behavior through septal CRFR2 but not hippocampal CRFR1
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Astressin and anti-SVG-30 completely prevented stress-induced anxiety when given by i.s.injection (Fig. 9c,d) but not by i.h.injection (data not shown) before the immobilization stress.”
§ Modulation of Learning and Anxiety by Corticotropin-Releasing Factor (CRF) and Stress: Differential Roles of CRF Receptors 1 and 2 > h/rCRF mediates stress-induced enhancement of fear conditioning through hippocampal CRFR1 and stressinduced anxiety through septal CRFR2
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- The authors state this as an assumption: The hippocampus and lateral intermediate septum play an important role in associative learning.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“However, i.s.injection of 500 ng h /rCRF per mouse significantly reduced the time spent (F (4,45) ϭ 4.32, p Ͻ 0.01) (Fig. 7a) and the number of entries (F (4,45) ϭ 4.11, p Ͻ 0.01) (Fig. 7b) on the open arms without affecting locomotor activity (data not shown), as revealed by the total distance crossed in 5 min.”
§ Modulation of Learning and Anxiety by Corticotropin-Releasing Factor (CRF) and Stress: Differential Roles of CRF Receptors 1 and 2 > h/rCRF induces anxious behavior through septal CRFR2 but not hippocampal CRFR1
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The specific action of CRF on learning was also supported by the observation that CRF-injected mice exhibited strong freezing to the context and tone used as conditioned stimuli, but this fear response did not generalize to a novel context.”
§ Modulation of Learning and Anxiety by Corticotropin-Releasing Factor (CRF) and Stress: Differential Roles of CRF Receptors 1 and 2 > The effects of CRF on fear conditioning are specific for memory consolidation
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Exposure of mice to immobilization stress produced sequential changes in anxiety and learning, as shown by a transiently increased anxiety after 30 min that disappeared after 1 hr, followed by enhanced acquisition of conditioned fear after 3 hr.”
§ Modulation of Learning and Anxiety by Corticotropin-Releasing Factor (CRF) and Stress: Differential Roles of CRF Receptors 1 and 2 > Septal CRFR2 mediates stress-induced anxiety, whereas hippocampal CRFR1 mediates stress-induced enhancement of fear conditioning
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The stress-induced increase of anxiety and fear conditioning could be fully prevented by septal and hippocampal CRFR antagonists, respectively, which under nonstress conditions did not affect either behavior by themselves.”
§ Modulation of Learning and Anxiety by Corticotropin-Releasing Factor (CRF) and Stress: Differential Roles of CRF Receptors 1 and 2 > Septal CRFR2 mediates stress-induced anxiety, whereas hippocampal CRFR1 mediates stress-induced enhancement of fear conditioning
hedgeddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Rests on an assumption: Immobilization stress increases endogenous CRF activity in the brain areas studied.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“So far, a role of CRFR2 and a relationship between CRFR1-and CRFR2-mediated behaviors of the brain CRF system have not been established.”
§ Modulation of Learning and Anxiety by Corticotropin-Releasing Factor (CRF) and Stress: Differential Roles of CRF Receptors 1 and 2 > Key words: CRF receptor 1; CRF receptor 2; fear conditioning; anxiety; stress; hippocampus; lateral septum
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: fails — The paper may give no reason why it holds.
Probably not a substantial claim. The paper may give no reason why it holds. It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“It was concluded that the observed effects reflected changes of associative learning and not arousal, attention, or motivation.”
boosteddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“CRF and Ucn exert their biological activity by binding to two types of CRF receptors (CRFRs), CRFR1 (Chen et al., 1993;Chang et al., 1993;Vita et al., 1993;Dautzenberg et al., 1998) and CRFR2 (L ovenberg et al., 1995;Perrin et al., 1995;Stenzel et al., 1995;K ishimoto et al., 1995), which show distinct distribution patterns in specific brain areas (Chalmers et al., 1995).”
§ Modulation of Learning and Anxiety by Corticotropin-Releasing Factor (CRF) and Stress: Differential Roles of CRF Receptors 1 and 2 > Key words: CRF receptor 1; CRF receptor 2; fear conditioning; anxiety; stress; hippocampus; lateral septum
What the sources say
- Not checked yetcites Chen et al., 1993
- Not checked yetcites Lovenberg et al., 1995
- Not checked yetcites Chalmers et al., 1995
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Interestingly, higher doses of CRF typically induce anxiety, whereas displacement of CRF from its binding protein even by high doses of CRF-BP ligands enhances learning without affecting anxiety (Dunn and Berridge, 1990;Behan et al., 1995).”
§ Modulation of Learning and Anxiety by Corticotropin-Releasing Factor (CRF) and Stress: Differential Roles of CRF Receptors 1 and 2 > Key words: CRF receptor 1; CRF receptor 2; fear conditioning; anxiety; stress; hippocampus; lateral septum
What the sources say
- Not checked yetcites Dunn and Berridge, 1990
- Not checked yetcites Behan et al., 1995
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“In addition, CRF and the novel CRF-like peptide urocortin (Ucn) are widely distributed throughout the C NS of rodents and humans (Olschowka et al., 1982;Cummings et al., 1983;Vaughan et al., 1995;Kozicz et al., 1998), where they affect numerous behaviors such as locomotor activity, anxiety, food intake, and learning (Sutton et al., 1982;Dunn and Berridge, 1990;De Souza, 1995).”
§ Modulation of Learning and Anxiety by Corticotropin-Releasing Factor (CRF) and Stress: Differential Roles of CRF Receptors 1 and 2 > Key words: CRF receptor 1; CRF receptor 2; fear conditioning; anxiety; stress; hippocampus; lateral septum
What the sources say
- Not checked yetcites Olschowka et al., 1982
- Not checked yetcites Vaughan et al., 1995
- Not checked yetcites Dunn and Berridge, 1990
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“The hippocampus appears to be required for context-dependent (Kim and Fanselow, 1992;Phillips and LeDoux, 1992) and tonedependent fear conditioning (Maren et al., 1997)”
§ Modulation of Learning and Anxiety by Corticotropin-Releasing Factor (CRF) and Stress: Differential Roles of CRF Receptors 1 and 2 > Key words: CRF receptor 1; CRF receptor 2; fear conditioning; anxiety; stress; hippocampus; lateral septum
What the sources say
- Not checked yetcites Kim and Fanselow, 1992
- Not checked yetcites Phillips and LeDoux, 1992
- Not checked yetcites Maren et al., 1997
hedgeddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“whereas the lateral septum mediates the impairment of conditioned fear responses (Thomas and Yadin, 1980;Yadin and Thomas, 1981; Garcia and Jaffard, 1996) and the enhancement of anxious behaviors (Menard and Treit, 1996).”
§ Modulation of Learning and Anxiety by Corticotropin-Releasing Factor (CRF) and Stress: Differential Roles of CRF Receptors 1 and 2 > Key words: CRF receptor 1; CRF receptor 2; fear conditioning; anxiety; stress; hippocampus; lateral septum
What the sources say
- Not checked yetcites Thomas and Yadin, 1980
- Not checked yetcites Yadin and Thomas, 1981
- Not checked yetcites Garcia and Jaffard, 1996
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Thus, these antagonists exhibited an effect opposite to the one of h /rCRF and suggested that fear conditioning was tonically impaired by septal CRFR2 but not by hippocampal CRFR1.”
§ Modulation of Learning and Anxiety by Corticotropin-Releasing Factor (CRF) and Stress: Differential Roles of CRF Receptors 1 and 2 > Modulation of fear conditioning by h/rCRF is restricted to a small time window
hedgeddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- The authors state this as an assumption: The hippocampus and lateral intermediate septum play an important role in associative learning.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The effect of post-training i.h.injection of h/rCRF to increase fear conditioning excluded the possibility that the observed effect was caused by attentional, motivational, or arousal effects.”
§ Modulation of Learning and Anxiety by Corticotropin-Releasing Factor (CRF) and Stress: Differential Roles of CRF Receptors 1 and 2 > The effects of CRF on fear conditioning are specific for memory consolidation
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Control experiments demonstrated that these effects were specifically mediated through the dorsal hippocampus and lateral intermediate septum but not through the neighboring brain areas or lateral ventricles.”
§ Modulation of Learning and Anxiety by Corticotropin-Releasing Factor (CRF) and Stress: Differential Roles of CRF Receptors 1 and 2 > DISCUSSION CRF-like peptides modulate fear conditioning in a region-specific manner
boosteddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- The authors state this as an assumption: The hippocampus and lateral intermediate septum play an important role in associative learning.
None of the sources cited for this claim have been checked yet.
In the paper
“In agreement with this observation, high levels of CRFR2␣ mRNA but not CRFR1 mRNA (Chalmers et al., 1995) or CRFR1 protein (Radulovic et al., 1998a) were found in the lateral intermediate septum.”
§ Modulation of Learning and Anxiety by Corticotropin-Releasing Factor (CRF) and Stress: Differential Roles of CRF Receptors 1 and 2 > DISCUSSION CRF-like peptides modulate fear conditioning in a region-specific manner
What the sources say
- Not checked yetcites Chalmers et al., 1995
- Not checked yetcites Radulovic et al., 1998a
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“It should be mentioned, however, that a recent study reported impairment of tone-dependent fear conditioning after neurotoxic and electrolytic lesions of the dorsal hippocampus (Maren et al., 1997), a region used for CRF-like peptide injections in our experiments.”
§ Modulation of Learning and Anxiety by Corticotropin-Releasing Factor (CRF) and Stress: Differential Roles of CRF Receptors 1 and 2 > The effects of CRF on fear conditioning are specific for memory consolidation
What the sources say
- Not checked yetcites Maren et al., 1997
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim.
In the paper
“Enhanced associative learning of tone-dependent fear through hippocampal CRFR1 could result from activation of hippocampal pathways to the amygdala (Henke, 1990), a brain region identified as being crucial for acquisition of fear responses.”
§ Modulation of Learning and Anxiety by Corticotropin-Releasing Factor (CRF) and Stress: Differential Roles of CRF Receptors 1 and 2 > The effects of CRF on fear conditioning are specific for memory consolidation
What the sources say
- Not checked yetcites Henke, 1990 source
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“However, enhancement of tonedependent fear, generally believed to be mediated by different neuronal circuits, contrasted with the common view that the hippocampal formation does not play a role in acquisition of tone-dependent fear.”
§ Modulation of Learning and Anxiety by Corticotropin-Releasing Factor (CRF) and Stress: Differential Roles of CRF Receptors 1 and 2 > The effects of CRF on fear conditioning are specific for memory consolidation
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Consistently, the high density of glucocorticoid receptors and almost restricted distribution of mineralocorticoid receptors was demonstrated in the lateral septum and hippocampus (Reul and De Kloet, 1985).”
§ Modulation of Learning and Anxiety by Corticotropin-Releasing Factor (CRF) and Stress: Differential Roles of CRF Receptors 1 and 2 > Septal CRFR2 mediates stress-induced anxiety, whereas hippocampal CRFR1 mediates stress-induced enhancement of fear conditioning
What the sources say
- Not checked yetcites Reul and De Kloet, 1985
boosted- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
The authors state this as an assumption.
The hippocampus and lateral intermediate septum play an important role in associative learning.
“These two regions, which contain different amounts of CRFR1, CRFR2, and CRF-BP, are assumed to play an important role in associative learning.”
The authors state this as an assumption.
Ucn may be the putative ligand for CRFR2.
“The observation that h/rCRF was more effective than Ucn in enhancing or impairing fear conditioning was surprising in view of the assumption that Ucn may be the putative ligand for CRFR2 and the finding that Ucn binds under defined conditions with higher affinity than h/rCRF to both CRFR1 and CRFR2 (Vaughan et al., 1995).”
The paper relies on this without support.
Immobilization stress increases endogenous CRF activity in the brain areas studied.
“The stress-induced increase of anxiety and fear conditioning could be fully prevented by septal and hippocampal CRFR antagonists, respectively, which under nonstress conditions did not affect either behavior by themselves.”
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
The cited source says what the claim attributes to it.
In the citing paper
“For example, LS injections of agonists of the type 2 corticotropin-releasing factor receptor (Crfr2) have resulted in increased anxiety (Radulovic et al., 1999; Bakshi et al., 2002; Henry et al., 2006).”
From Control of Stress-Induced Persistent Anxiety by an Extra-Amygdala Septohypothalamic Circuit (2014) · cites this paper as Radulovic et al., 1999
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
Each contradiction between two passages listed here was confirmed by an independent check.
Rated minor: it would not touch a result — a value no result rests on, a p-value that stays on the same side of the significance level, or a conflict that is clerical, resolved elsewhere in the paper, or outside its own findings.
In the paper
§ Modulation of Learning and Anxiety by Corticotropin-Releasing Factor (CRF) and Stress: Differential Roles of CRF Receptors 1 and 2 > CRF-like peptides modulate fear conditioning in a brain region-specific manner
“fear conditioning to both context, F (12,103) ϭ 5.158, p Ͻ 0.001 (Fig. 1a)”
§ Modulation of Learning and Anxiety by Corticotropin-Releasing Factor (CRF) and Stress: Differential Roles of CRF Receptors 1 and 2 > Septal CRFR2 mediates stress-induced anxiety, whereas hippocampal CRFR1 mediates stress-induced enhancement of fear conditioning
“Figure 1.Anatomical localization of the injection sites for CRF receptor agonists and antagonists.”
Rated minor: it would not touch a result — a value no result rests on, a p-value that stays on the same side of the significance level, or a conflict that is clerical, resolved elsewhere in the paper, or outside its own findings.
In the paper
§ Modulation of Learning and Anxiety by Corticotropin-Releasing Factor (CRF) and Stress: Differential Roles of CRF Receptors 1 and 2 > CRF-like peptides modulate fear conditioning in a brain region-specific manner
“Injection of CRF-like peptides into the parietal somatosensory cortex and striatum, brain regions adjacent to the hippocampus and septum, respectively, did not produce any significant effects on contextand tone-dependent fear conditioning (Fig. 3c,d).”
§ Modulation of Learning and Anxiety by Corticotropin-Releasing Factor (CRF) and Stress: Differential Roles of CRF Receptors 1 and 2 > Septal CRFR2 mediates stress-induced anxiety, whereas hippocampal CRFR1 mediates stress-induced enhancement of fear conditioning
“Context-and tone-dependent fear conditioning after i.h. ( a), i.s. ( b), intracortical ( c), or intracaudate ( e) injection of 20 pmol peptide per mouse.”
Citations
Cites
The Mouse Brain in Stereotaxic Coordinates
Paxinos, G. (2001) · Cited by 12,859
Vale, W., Spiess, J., Rivier, C., & Rivier, J. (1981) · Science · doi:10.1126/science.6267699 · Cited by 3,965
Self-citationVale, W., Spiess, J., RIVIER, C. L., & Rivier, J. (1982) · Obstetrical & Gynecological Survey · doi:10.1097/00006254-198205000-00013 · Cited by 3,904
Self-citationDifferential contribution of amygdala and hippocampus to cued and contextual fear conditioning.
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Two receptor systems for corticosterone in rat brain: Microdistribution and differential occupation
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Metadata
- Authors
- Radulovic, J., Rühmann, A., Liepold, T., & Spiess, J.
- Affiliations
- Max Planck Institute of Experimental Medicine (DE)
- ORCID
- Liepold, Thomas
- Venue
- The Journal of Neuroscience
- Publisher
- Society for Neuroscience
- Published
- 1999-06-15
- Volume
- 19
- Issue
- 12
- Pages
- 5016-5025
- ISSN
- 0270-6474 (ISSN-L)
- 1529-2401
- PMC
- PMC6782638
- OpenAlex
- W1633118497
- Cited by
- 402
- References
- 55
- Citations by year
- 2026: 3 · 2025: 4 · 2024: 1 · 2023: 3 · 2022: 3 · 2021: 11 · 2020: 6 · 2019: 8 · 2018: 5 · 2017: 11 · 2016: 8 · 2015: 13 · 2014: 14 · 2013: 15 · 2012: 14
- FWCI
- 15.06
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Neuroscience (publishedVersion, cc-by-nc-sa)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Max-Planck-Gesellschaft
- Topics
- Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuropeptides and Animal Physiology
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Keywords
- corticotropin-releasing factor, CRF1 receptor, CRF receptor 2, fear conditioning, memory consolidation, anxiety, dorsal hippocampus, astressin, antisauvagine-30, restraint stress, stress response, associative learning
- MeSH terms
- CRF Receptor, Type 1, Acoustic Stimulation, Animals, Anxiety, Behavior, Animal, Brain Chemistry, Conditioning, Psychological, Corticotropin-Releasing Hormone, Dose-Response Relationship, Drug, Fear, Hippocampus, Male, Mice, Inbred BALB C, Peptide Fragments, Septal Nuclei, Stress, Psychological, Receptors, Corticotropin-Releasing Hormone, Neuroprotective Agents, Maze Learning, Mice
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Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
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