The DOI matches its Crossref record; 32 of the 32 references it cites were found in a registry or an index; none of the 19 sources its claims cite is checked for support yet.
Amygdala circuitry mediating reversible and bidirectional control of anxiety
Open accessAbstract
Anxiety—a sustained state of heightened apprehension in the absence of immediate threat—becomes severely debilitating in disease states. Anxiety disorders represent the most common of psychiatric diseases (28% lifetime prevalence) and contribute to the aetiology of major depression and substance abuse. Although it has been proposed that the amygdala, a brain region important for emotional processing, has a role in anxiety, the neural mechanisms that control anxiety remain unclear. Here we explore the neural circuits underlying anxiety-related behaviours by using optogenetics with two-photon microscopy, anxiety assays in freely moving mice, and electrophysiology. With the capability of optogenetics to control not only cell types but also specific connections between cells, we observed that temporally precise optogenetic stimulation of basolateral amygdala (BLA) terminals in the central nucleus of the amygdala (CeA)—achieved by viral transduction of the BLA with a codon-optimized channelrhodopsin followed by restricted illumination in the downstream CeA—exerted an acute, reversible anxiolytic effect. Conversely, selective optogenetic inhibition of the same projection with a third-generation halorhodopsin (eNpHR3.0) increased anxiety-related behaviours. Importantly, these effects were not observed with direct optogenetic control of BLA somata, possibly owing to recruitment of antagonistic downstream structures. Together, these results implicate specific BLA–CeA projections as critical circuit elements for acute anxiety control in the mammalian brain, and demonstrate the importance of optogenetically targeting defined projections, beyond simply targeting cell types, in the study of circuit function relevant to neuropsychiatric disease.
Overview
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
16 Own result · 8 Not checked yet · 6 Own method · 5 Own interpretation · 2 No basis given
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
“without impaired locomotion (Supplementary Fig. 4)”
§ Amygdala circuitry mediating reversible and bidirectional control of anxiety > Abstract
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
“A higher proportion of CeL neurons expressed c-fos in the ChR2:BLA-CeA group relative to the eYFP:BLA-CeA group (F2,9=4.54, p=0.04)”
§ Amygdala circuitry mediating reversible and bidirectional control of anxiety > Abstract
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 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
“Illumination of BLA terminals in CeL elicited excitatory responses in both weakly- and strongly-connected CeL cells (n=16; Fig. 2c).”
§ Amygdala circuitry mediating reversible and bidirectional control of anxiety > Abstract
plaindirectn = 16- 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
“in acute slices time-locked light-evoked excitatory responses were abolished upon bath application of 2,3-dihydroxy-6-nitro-7-sulfamoyl-benzo[f] quinoxaline-2,3-dione (NBQX) and (2R)-amino-5-phosphonopentanoate (AP5) (Supplementary Fig. 10).”
§ Amygdala circuitry mediating reversible and bidirectional control of anxiety > Abstract
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
“Indeed, we observed potent spiking inhibition in CeM cells upon illumination of BLA-CeL terminals (Fig. 2d; F2,11=15.35, p=0.004).”
§ Amygdala circuitry mediating reversible and bidirectional control of anxiety > Abstract
plaindirectn = 7- 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 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
“BLA somata inhibition did not induce an anxiogenic response, perhaps owing to the simultaneous decrease in direct BLA-CeM excitatory input.”
§ Amygdala circuitry mediating reversible and bidirectional control of anxiety > Abstract
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
“as well as increased center time in the OFT (F1,105=24.46, p<0.00001; Fig. 1d,e), reflecting anxiety reduction”
§ Amygdala circuitry mediating reversible and bidirectional control of anxiety > Abstract
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
“Photostimulation of BLA terminals in the CeA (ChR2:BLA-CeA) increased open-arm time (F1,42=69.09, p<0.00001; Fig. 1b,c)”
§ Amygdala circuitry mediating reversible and bidirectional control of anxiety > Abstract
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
“Thus, the in vivo illumination of BLA-CeA projections that triggered acute anxiolysis was found to excite CeL neurons without activating all BLA somata nonspecifically.”
§ Amygdala circuitry mediating reversible and bidirectional control of anxiety > Abstract
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 eNpHR3.0:BLA-CeA group showed elevated levels of c-fos expression, relative to the eYFP:BLA-CeA and eNpHR3.0:BLA(somata) groups, in the CeM (p<0.05; Supplementary Fig. 12)”
§ Amygdala circuitry mediating reversible and bidirectional control of anxiety > Abstract
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 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
“and probability of open-arm entry from the maze center (F1,42=24.69, p<0.00001: Fig. 1c inset; Supplementary Movie) on the EPM”
§ Amygdala circuitry mediating reversible and bidirectional control of anxiety > Abstract
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 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
“Importantly, these effects were not observed with direct optogenetic control of BLA somata, possibly owing to recruitment of antagonistic downstream structures.”
§ Amygdala circuitry mediating reversible and bidirectional control of anxiety > Abstract
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
“intra-CeA glutamate receptor antagonism abolished light-induced reductions in anxiety as measured by open-arm time (F1,35=8.61; p=0.008) and probability of open-arm entry on the EPM (F1,35=5.92, p=0.02), and center time during the OFT (F1,77=13.99; p=0.0006; Fig. 3c,d).”
§ Amygdala circuitry mediating reversible and bidirectional control of anxiety > Abstract
plaindirectn = 8 ·- 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 marked difference between effective synaptic transmission and antidromic spiking fidelity (p=0.0039; Fig. 3b, inset) reveals that optogenetically-driven vesicle release may occur in the absence of reliable antidromic drive”
§ Amygdala circuitry mediating reversible and bidirectional control of anxiety > Abstract
hedgedconditionaln = 7- 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.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“eNpHR3.0 expression was restricted to glutamatergic neurons in the BLA”
§ Amygdala circuitry mediating reversible and bidirectional control of anxiety > Abstract
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.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“No group differences were detected in the proportion of eYFP-positive cells within each region (Supplementary Fig. 5).”
§ Amygdala circuitry mediating reversible and bidirectional control of anxiety > Abstract
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.
In the paper
“These data from a structurally- and functionally-identified microcircuit25 illustrate that the balance of direct and indirect inputs from the BLA to the CeM can modulate CeM activity.”
§ Amygdala circuitry mediating reversible and bidirectional control of anxiety > Abstract
What the sources say
- Not checked yetcites [25] Davis, M. in The Amygdala: A Functional Analysis (ed. Aggleton, J. P. ) 213–288 (Oxford Univ. Press, 2000) source
plainconditionaln = 7- 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.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“Importantly, drug treatment did not impair locomotor activity (Supplementary Fig. 9)”
§ Amygdala circuitry mediating reversible and bidirectional control of anxiety > Abstract
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 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
“suggests that multiple subpopulations or projections of BLA neurons can act in opposition (e.g. direct excitation of CeM along with feed-forward inhibition of CeM).”
§ Amygdala circuitry mediating reversible and bidirectional control of anxiety > Abstract
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
“Here, we have identified the BLA-CeL pathway as a neural substrate for real-time bidirectional modulation of the unconditioned expression of anxiety.”
§ Amygdala circuitry mediating reversible and bidirectional control of anxiety > Abstract
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
“since BLA neurons excite GABAergic CeL neurons26 that provide feed-forward inhibition onto CeM “output” neurons6,18,19”
§ Amygdala circuitry mediating reversible and bidirectional control of anxiety > Abstract
What the sources say
- Not checked yetcites [26] Pitkanen, A. in The Amygdala: A Functional Analysis (ed. Aggleton, J. P. ) 31–99 (Oxford Univ. Press, 2000) source
- Not checked yetcites [6] Pare, D., Quirk, G. J. & Ledoux, J. E. New vistas on amygdala networks in conditioned fear. J. Neurophysiol. 92, 1–9 (2004) source
- Not checked yetcites [18] Ciocchi, S. et al. Encoding of conditioned fear in central amygdala inhibitory circuits. Nature 468, 277–282 (2010) source
- Not checked yetcites [19] Haubensak, W. et al. Genetic dissection of an amygdala microcircuit that gates conditioned fear. Nature 468, 270–276 (2010) source
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 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 findings demonstrate that anxiety is continuously regulated by balanced antagonistic pathways within the amygdala”
§ Amygdala circuitry mediating reversible and bidirectional control of anxiety > Abstract
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
“consistent with the hypothesis that inhibition of BLA-CeL synapses suppresses feed-forward inhibition from CeL neurons to CeM neurons, thereby increasing CeM excitability and the downstream processes leading to increased anxiety phenotypes.”
§ Amygdala circuitry mediating reversible and bidirectional control of anxiety > Abstract
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. 9
- 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
“Selective illumination of eNpHR3.0-expressing axon terminals reduced the probability of both spontaneously occurring (frequency: F1,8=32.99, p=0.00024; amplitude: F1,8=21.96, p=0.001; Supplementary Fig. 13) and electrically-evoked (F1,10=10.79, p=0.006; Fig. 4a) vesicle release, without preventing spiking at the soma (Supplementary Fig. 14).”
§ Amygdala circuitry mediating reversible and bidirectional control of anxiety > Abstract
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
“Of the BLA neurons sampled (n=18, Supplementary Fig. 7); 44% projected to the CeL alone and 17% projected to the CeM alone, with only one cell observed to project to both the CeL and the CeM.”
§ Amygdala circuitry mediating reversible and bidirectional control of anxiety > Abstract
plainn = 18- 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 very same CeM neurons (n=7) showed net excitation upon broad illumination of BLA inputs to the CeM (Fig. 2e), but showed net inhibition upon selective illumination of BLA inputs to the CeL (Fig. 2f).”
§ Amygdala circuitry mediating reversible and bidirectional control of anxiety > Abstract
plaindirectn = 7- 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
“We also found that the eNpHR3.0:BLA-CeA group showed reduced open-arm time and probability of open-arm entry on EPM (F1,40=21.08, p<0.00001; and F1,40=19.93, p<0.00001, respectively; Fig. 4b,c) and center-time in the OFT (F1,100=18.919, p<0.00001; Fig. 4d,e) during photostimulation when compared to the eYFP and BLA(somata) groups, without altering locomotor activity”
§ Amygdala circuitry mediating reversible and bidirectional control of anxiety > Abstract
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
“The primary output region of the amygdala is the CeM23,24 which (when chemically or electrically excited) mediates autonomic and behavioral responses associated with fear and anxiety via projections to the brainstem25.”
§ Amygdala circuitry mediating reversible and bidirectional control of anxiety > Abstract
What the sources say
- Not checked yetcites [23] Krettek, J. E. & Price, J. L. A description of the amygdaloid complex in the rat and cat with observations on intra-amygdaloid axonal connections. J. Comp. Neurol. 178, 255–279 (1978) source
- Not checked yetcites [24] Krettek, J. E. & Price, J. L. Amygdaloid projections to subcortical structures within the basal forebrain and brainstem in the rat and cat. J. Comp. Neurol. 178, 225–253 (1978) source
- Not checked yetcites [25] Davis, M. in The Amygdala: A Functional Analysis (ed. Aggleton, J. P. ) 213–288 (Oxford Univ. Press, 2000) source
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
“our findings do not exclude downstream or parallel circuits including the BNST28, the insular and prefrontal cortices29, and the septal-hippocampal circuit30”
§ Amygdala circuitry mediating reversible and bidirectional control of anxiety > Abstract
What the sources say
- Not checked yetcites [28] Davis, M., Walker, D. L., Miles, L. & Grillon, C. Phasic vs sustained fear in rats and humans: role of the extended amygdala in fear vs anxiety. Neuropsychopharmacology 35, 105–135 (2010) source
- Not checked yetcites [29] Shin, L. M. & Liberzon, I. The neurocircuitry of fear, stress, and anxiety disorders. Neuropsychopharmacology 35, 169–191 (2010) source
- Not checked yetcites [30] Gray, J. A. & McNaughton, N. The neuropsychology of anxiety: reprise. Nebr. Symp. Motiv. 43, 61–134 (1996)
plain- 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.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“Quantitative analyses of confocal images were performed with both staining and analysis blind to experimental condition.”
§ Amygdala circuitry mediating reversible and bidirectional control of anxiety > Methods Summary > Opsin expression validation and immunohistochemistry
plain- 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.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“but no detectable difference between the ChR2:BLA-CeA and eYFP:BLA-CeA groups, indicating that the bevelled cannula shielding effectively prevented BLA somata photostimulation.”
§ Amygdala circuitry mediating reversible and bidirectional control of anxiety > Abstract
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.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“The BLA is primarily glutamatergic (~90%)20, 21 while the CeA, which encompasses the centrolateral (CeL) and centromedial (CeM) nuclei, consists of ~95% GABAergic medium spiny neurons22.”
§ Amygdala circuitry mediating reversible and bidirectional control of anxiety > Abstract
What the sources say
- Not checked yetcites [20] Carlsen, J. Immunocytochemical localization of glutamate decarboxylase in the rat basolateral amygdaloid nucleus, with special reference to GABAergic innervation of amygdalostriatal projection neurons. J. Comp. Neurol. 273, 513–526 (1988) source
- Not checked yetcites [21] Smith, Y. & Pare, D. Intra-amygdaloid projections of the lateral nucleus in the cat: PHA-L anterograde labeling combined with postembedding GABA and glutamate immunocytochemistry. J. Comp. Neurol. 342, 232–248 (1994) source
- Not checked yetcites [22] McDonald, A. J. Cytoarchitecture of the central amygdaloid nucleus of the rat. J. Comp. Neurol. 208, 401–418 (1982) source
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.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“Opsin expression was specific to BLA glutamatergic neurons, and was not observed in intercalated cells (Supplementary Fig. 6).”
§ Amygdala circuitry mediating reversible and bidirectional control of anxiety > Abstract
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.
None of the sources cited for this claim have been checked yet.
In the paper
“These data are consistent with reports implicating CeA involvement in anxiety9,11,12”
§ Amygdala circuitry mediating reversible and bidirectional control of anxiety > Abstract
What the sources say
- Not checked yetcites [9] Kalin, N. H., Shelton, S. E. & Davidson, R. J. The role of the central nucleus of the amygdala in mediating fear and anxiety in the primate. J. Neurosci. 24, 5506–5515 (2004) source
- Not checked yetcites [11] Etkin, A., Prater, K. E., Schatzberg, A. F., Menon, V. & Greicius, M. D. Disrupted amygdalar subregion functional connectivity and evidence of a compensatory network in generalized anxiety disorder. Arch. Gen. Psychiatry 66, 1361–1372 (2009) source
- Not checked yetcites [12] Lyons, A. M. & Thiele, T. E. Neuropeptide Y conjugated to saporin alters anxiety-like behavior when injected into the central nucleus of the amygdala or basomedial hypothalamus in BALB/cJ mice. Peptides 31, 2193–2199 (2010) source
plaincorrelational- 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.
In the paper
“for example, stress induces CeL release of corticotropin releasing hormone (CRH) in the BNST28.”
§ Amygdala circuitry mediating reversible and bidirectional control of anxiety > Abstract
What the sources say
- Not checked yetcites [28] Davis, M., Walker, D. L., Miles, L. & Grillon, C. Phasic vs sustained fear in rats and humans: role of the extended amygdala in fear vs anxiety. Neuropsychopharmacology 35, 105–135 (2010) source
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.
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 data demonstrate that the light-induced anxiolytic effects were caused by the activation of BLA-CeA synapses, and not attributable to BLA projections to distal targets passing through the CeA.”
§ Amygdala circuitry mediating reversible and bidirectional control of anxiety > Abstract
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.
In the paper
“two well-validated27 anxiety assays: the elevated-plus maze (EPM) and the open-field test (OFT; Fig. 1a–e).”
§ Amygdala circuitry mediating reversible and bidirectional control of anxiety > Abstract
What the sources say
- Not checked yetcites [27] Carola, V., D’Olimpio, F., Brunamonti, E., Mangia, F. & Renzi, P. Evaluation of the elevated plus-maze and open-field tests for the assessment of anxiety-related behaviour in inbred mice. Behav. Brain Res. 134, 49–57 (2002) source
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.
Probably not a substantial claim.
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 source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“Conventionally used AAV backbones which include a commonly used neuronal expression cassette composed of 1.3 kb CaMKIIα promoter (which shows comparable expression efficiency with 0.4 kb CaMKIIα promoter [10] used in CWB), WPRE, and human growth hormone polyadenylation signal [23-25] has a capacity of 2.4 kb.”
From Optimization of AAV expression cassettes to improve packaging capacity and transgene expression in neurons (2014) · cites this paper as [23]
Experimental — accuracy not yet measuredThe cited source says what the claim attributes to it.
In the citing paper
“This contrast notwithstanding, the neural systems implicated in anxiety by rodent studies are consistent with those identified in human patients26-34, underscoring the utility and translatability of these rodent studies.”
From Resolving the neural circuits of anxiety (2015) · cites this paper as [33]
In the citing paper
“In addition to a role in fear and threat conditioning, the amygdala also regulates anxiety.”
From A framework for understanding the emerging role of corticolimbic-ventral striatal networks in OCD-associated repetitive behaviors (2015) · cites this paper as Tye et al., 2011
In the citing paper
“Moreover, photoactivation of BLA somata increases measures of innate anxiety33, as well as learned inhibitory avoidance80.”
From Resolving the neural circuits of anxiety (2015) · cites this paper as [33]
In the citing paper
“For example, photostimulation of excitatory basolateral amygdala projections to central amygdala resulted in an acute anxiolytic effect that rapidly dissipated upon cessation of stimulation (Tye et al., 2011).”
From Control of Stress-Induced Persistent Anxiety by an Extra-Amygdala Septohypothalamic Circuit (2014) · cites this paper as Tye et al., 2011
Citations
Cites
Kessler, R. C., Berglund, P., Demler, O., Jin, R., Merikangas, K. R., & Walters, E. E. (2005) · Archives of General Psychiatry · doi:10.1001/archpsyc.62.6.593 · Cited by 20,391
Millisecond-timescale, genetically targeted optical control of neural activity
Boyden, E. S., Zhang, F., Bamberg, E., Nagel, G., & Deisseroth, K. A. (2005) · Nature Neuroscience · doi:10.1038/nn1525 · Cited by 5,015
Self-citationThe Neurocircuitry of Fear, Stress, and Anxiety Disorders
Shin, L. M., & Liberzon, I. (2010) · Neuropsychopharmacology · doi:10.1038/npp.2009.83 · Cited by 2,083
The Emotional Brain, Fear, and the Amygdala
LeDoux, J. (2003) · Cellular and Molecular Neurobiology · doi:10.1023/a:1025048802629 · Cited by 1,818
Stress, memory and the amygdala
Roozendaal, B., McEwen, B. S., & Chattarji, S. (2009) · Nature Reviews Neuroscience · doi:10.1038/nrn2651 · Cited by 1,760
Phasic vs Sustained Fear in Rats and Humans: Role of the Extended Amygdala in Fear vs Anxiety
Davis, M., Walker, D. L., Miles, L., & Grillon, C. (2010) · Neuropsychopharmacology · doi:10.1038/npp.2009.109 · Cited by 1,513
Krettek, J. E., & Price, J. L. (1978) · Journal of Comparative Neurology · doi:10.1002/cne.901780204 · Cited by 1,293
Molecular and Cellular Approaches for Diversifying and Extending Optogenetics
Gradinaru, V., Zhang, F., Ramakrishnan, C., Mattis, J., Prakash, R., Diester, I., Goshen, I., Thompson, K. R., & Deisseroth, K. A. (2010) · Cell · doi:10.1016/j.cell.2010.02.037 · Cited by 1,040
Self-citationTargeting abnormal neural circuits in mood and anxiety disorders: from the laboratory to the clinic
Ressler, K. J., & Mayberg, H. S. (2007) · Nature Neuroscience · doi:10.1038/nn1944 · Cited by 1,007
The Amygdala: a functional analysis
Aggleton, J. P. (2000) · Cited by 966
Cited by
Sorted by citations
Resting-state connectivity biomarkers define neurophysiological subtypes of depression
Drysdale, A. T., Grosenick, L., Downar, J., Dunlop, K., Mansouri, F., Meng, Y., Fetcho, R. N., Zebley, B., Oathes, D. J., Etkin, A., et al. (2017) · Nature Medicine · doi:10.1038/nm.4246 · Cited by 2,170
Self-citationFrom circuits to behaviour in the amygdala
Janak, P. H., & Tye, K. M. (2015) · Nature · doi:10.1038/nature14188 · Cited by 2,011
Self-citationOptogenetics in neural systems
Yizhar, O., Fenno, L. E., Davidson, T. J., Mogri, M., & Deisseroth, K. (2011) · Neuron · doi:10.1016/j.neuron.2011.06.004 · Cited by 1,881
Self-citationThe development and application of optogenetics
Fenno, L., Yizhar, O., & Deisseroth, K. (2011) · Annual Review of Neuroscience · doi:10.1146/annurev-neuro-061010-113817 · Cited by 1,822
Self-citationOptogenetic stimulation of a hippocampal engram activates fear memory recall
Liu, X., Ramirez, S., Pang, P. T., Puryear, C. B., Govindarajan, A., Deisseroth, K. A., & Tonegawa, S. (2012) · Nature · doi:10.1038/nature11028 · Cited by 1,669
Self-citation
Metadata
- Authors
- Tye, K. M., Prakash, R., Kim, S.-Y., Fenno, L. E., Grosenick, L., Zarabi, H., Thompson, K. R., Gradinaru, V., Ramakrishnan, C., & Deisseroth, K.
- Affiliations
- Stanford University (US)
- Howard Hughes Medical Institute (US)
- Corresponding author
- Deisseroth, Karl
- ORCID
- Venue
- Nature
- Published
- 2011-03
- Volume
- 471
- Issue
- 7338
- Pages
- 358-362
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- PMC
- PMC3154022
- OpenAlex
- W2060978874
- Semantic Scholar
- ffc80185f7540e58c28aead0cf3752801f320eb3
- Cited by
- 1,289
- References
- 32
- Citations by year
- 2026: 62 · 2025: 73 · 2024: 86 · 2023: 73 · 2022: 76 · 2021: 97 · 2020: 91 · 2019: 84 · 2018: 85 · 2017: 70 · 2016: 100 · 2015: 97 · 2014: 92 · 2013: 76 · 2012: 87
- FWCI
- 47.77
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- CaltechAUTHORS (California Institute of Technology) (submittedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- Seoul National University Open Repository (Seoul National University) (submittedVersion)
- Funders
- National Institutes of Health (DP1OD000616)
- National Institute of Mental Health (F32MH088010, R01MH075957)
- National Institute on Drug Abuse (R01DA020794)
- National Institute of Diabetes and Digestive and Kidney Diseases (DP2DK102256)
- Topics
- Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Keywords
- anxiety, amygdala, central amygdala, basolateral amygdala, neural circuits, anxiolytic effects, bidirectional control, optogenetic stimulation, optogenetic inhibition, channelrhodopsin, halorhodopsin, fear memory, anxiety disorders, rats, mice
- MeSH terms
- Amygdala, Animals, Anxiety, Anxiety Disorders, Light, Models, Neurological, Neural Pathways, Neurons, Stress, Physiological, Synapses, Halorhodopsins, Mice
About these checks
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.
A language model drew the claims from the paper on 2026-10-04, under version 3 of the claim definition (model deepseek-v4.1-flash, prompt extract-v3).
A second model labelled each claim on 2026-10-04 (model jev-1.13-20260917, definition revision gold-guideline-v0.2).
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
