The DOI matches its Crossref record; 60 of the 60 references it cites were found in a registry or an index; 2 of the 37 sources its claims cite were checked for support.
Optical activation of lateral amygdala pyramidal cells instructs associative fear learning
Open accessAbstract
Humans and animals can learn that specific sensory cues in the environment predict aversive events through a form of associative learning termed fear conditioning. This learning occurs when the sensory cues are paired with an aversive event occuring in close temporal proximity. Activation of lateral amygdala (LA) pyramidal neurons by aversive stimuli is thought to drive the formation of these associative fear memories; yet, there have been no direct tests of this hypothesis. Here we demonstrate that viral-targeted, tissue-specific expression of the light-activated channelrhodopsin (ChR2) in LA pyramidal cells permitted optical control of LA neuronal activity. Using this approach we then paired an auditory sensory cue with optical stimulation of LA pyramidal neurons instead of an aversive stimulus. Subsequently presentation of the tone alone produced behavioral fear responses. These results demonstrate in vivo optogenetic control of LA neurons and provide compelling support for the idea that fear learning is instructed by aversive stimulus-induced activation of LA pyramidal cells.
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TL;DR
Viral expression of channelrhodopsin in lateral amygdala (LA) pyramidal cells allowed optical stimulation to substitute for an aversive shock unconditioned stimulus (US), and pairing this stimulation with an auditory cue produced associative fear learning and 24-h memory. The results support the idea that aversive stimulus-induced activation of LA pyramidal cells can instruct fear learning.
Key findings
- ChR2/YFP expression was largely restricted to CaMKII-expressing pyramidal neurons (92 ± 1%) and very low in GABA-expressing cells (1.8 ± 0.0%).
- In vivo, 20-Hz laser stimulation with 10-ms pulses produced robust, reliable action potential firing in LA cells (total n = 15 cells from four animals) and activated large numbers of LA neurons, with 253 ± 46 CFOS+ cells/section on the stimulated side versus 29 ± 4 on the nonstimulated side (n = 3 animals); total CaMKII+ cells were 402 ± 37 per LA section.
- In behaving rats, pairing an auditory CS with laser stimulation of LA pyramidal cells as the US produced greater CS-evoked freezing than GFP/paired or ChR2/unpaired controls, with a significant trial block × treatment interaction (F6,63 = 4.7795, P = 0.00045).
- At 24-h long-term memory testing in a separate context, ChR2/paired animals froze significantly more than GFP/paired and ChR2/unpaired animals (one-way ANOVA F2,21 = 5.41, P = 0.013; post hoc P = 0.017 for both comparisons).
Methods
- Male Sprague-Dawley rats (275–300 g) received unilateral LA injections of AAV-CaMKII-ChR2/EYFP or AAV-CaMKII-GFP, with guide cannulae for fiber-optic laser stimulation; experiments included immunocytochemistry, in vivo electrophysiology, CFOS mapping, and behavioral fear conditioning.
- For conditioning, paired groups received 16 CS–US pairings: a 20-s auditory CS (5-kHz tone pips, 1 Hz, 250 ms on/750 ms off) coterminating with a 2-s laser US (20 Hz, 10-ms pulses); an unpaired group received 16 CS and 16 laser US presentations randomly and explicitly unpaired.
- Freezing was scored by a blind rater during training and during two CS presentations 24 h later in a novel context; data were analyzed with repeated-measures ANOVA, one-way ANOVA, and Newman–Keuls post hoc tests.
Limitations
- The paper states that freezing scores during long-term memory testing were relatively low compared with those typically obtained with an electric shock US, and it discusses possible explanations, including the need for plasticity in other fear-circuit regions, more specific cell targeting, or coactivation of neuromodulatory systems for maximal memory formation.
- The paper notes that laser stimulation itself produced a small but statistically significant amount of unconditioned freezing (paired t5 = 4.89, P = 0.005).
- Evident from the text: behavioral groups were small (n = 8 per group), CFOS and electrophysiology samples were limited (n = 3 animals; n = 15 cells), only male rats were used, and 3 ChR2/paired and 2 ChR2/unpaired animals were excluded because ChR2 expression or cannula placement criteria were not met.
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Claims the paper makes
16 Own result · 11 Not checked yet · 9 Own interpretation · 7 Own method · 2 No basis given · 1 Partly supported · accuracy not yet measured
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In the paper
“Several lines of indirect evidence support the idea that this plasticity occurs as a result of a Hebbian mechanism through which depolarization of LA pyramidal neurons by the shock US coincident with weaker activation of the same cells by auditory CS inputs results in fear learning (8–18).”
What the sources say
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Split into 2 atoms — 0 confirmed, 2 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.
- Not checked yetcites [11] Goosens KA, Hobin JA, Maren S. Auditory-evoked spike firing in the lateral amygdala and Pavlovian fear conditioning: Mnemonic code or fear bias? Neuron. 2003;40:1013–1022. doi: 10.1016/s0896-6273(03)00728-1. [DOI] [PubMed] [Google Scholar] source
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Split into 2 atoms — 0 confirmed, 2 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.
- Not checked yetcites [15] Rodrigues SM, Schafe GE, LeDoux JE. Intra-amygdala blockade of the NR2B subunit of the NMDA receptor disrupts the acquisition but not the expression of fear conditioning. J Neurosci. 2001;21:6889–6896. doi: 10.1523/JNEUROSCI.21-17-06889.2001. [DOI] [PMC free article] [PubMed] [Google Scholar] source
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hedgeddirect- 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
“Laser stimulation at 20 Hz produced significantly more action potential firing than either constant illumination or eyelid shock, whereas the latter two activated comparable levels of action potential firing (Fig. S3).”
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
“Laser stimulation at 20 Hz produced significantly more action potential firing than either constant illumination or eyelid shock, whereas the latter two activated comparable levels of action potential firing (Fig. S3).”
- Also stated in: § Discussion · hedged
“However, the CFOS experiments reported here demonstrate that large numbers of LA neurons were activated by laser stimulation and the electrophysiology experiments provide evidence that 20-Hz laser stimulation caused more action potential firing in LA cells than a shock US, suggesting that these were not the reasons for lower levels of fear learning.”
plaindirect- Asserted: passes — The authors put it forward as true.
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- Also stated in: § Discussion · hedged
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 fact, using the same fear conditioning protocol, we also found substantial levels of fear conditioning induced by a unilateral eyelid shock US (see Fig. S6 for comparison of shock vs. laser stimulation US-induced learning).”
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“Because using constant illumination to stimulate LA neurons produced similar levels of action potential firing as that evoked by eyelid shocks (Fig. S3), we also used 2-s constant laser illumination as an US (instead of 10-ms laser pulses at 20 Hz described above) and found that this stimulation protocol produced similar levels of fear conditioning (Fig. S5) to that evoked by the 20-Hz laser US.”
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
“During training, ChR2/paired animals froze significantly more to the CS than the GFP/paired and ChR2/unpaired groups especially later in training (Fig. 3A).”
- Also stated in: § Results · boosted
“post hoc comparisons demonstrated that CS-evoked freezing responses in ChR2/paired animals during trial blocks 3 and 4 were significantly greater than CS freezing responses in GFP/paired (P = 0002 and P = 0.0001 respectively) or ChR2/unpaired (P = 002 and P = 0.0001, respectively) groups.”
boosteddirectn = 8- Asserted: passes — The authors put it forward as true.
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- Also stated in: § Results · boosted
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
“Here we demonstrate that viral-targeted, tissue-specific expression of the light-activated channelrhodopsin (ChR2) in LA pyramidal cells permitted optical control of LA neuronal activity.”
- Also stated in: § Abstract · boosted
“These results demonstrate in vivo optogenetic control of LA neurons and provide compelling support for the idea that fear learning is instructed by aversive stimulus-induced activation of LA pyramidal cells.”
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.
- Also stated in: § Abstract · boosted
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 evoked firing rate was similar across different laser stimulation frequencies and laser pulse durations, evoked AP reliability was higher at lower frequencies (Fig. 2A and Fig. S2; total n = 15 cells from four animals).”
plaincorrelationaln = 15- Asserted: passes — The authors put it forward as true.
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In the paper
“ChR2 expression was found to be largely restricted to CaMKII-expressing pyramidal neurons (92 ± 1%; Fig. 1 B and C) and expressed at very low levels in GABA-expressing cells (1.8 ± 0.0%; Fig. 1B and Fig. S1).”
plaincorrelational- 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
“Using this approach we then paired an auditory sensory cue with optical stimulation of LA pyramidal neurons instead of an aversive stimulus. Subsequently presentation of the tone alone produced behavioral fear responses.”
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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- It may state two separate claims as one. 6
- Probably not a substantial claim. 15
In the paper
“Although optical stimulation of LA pyramidal neurons produced some freezing behavior, these levels were considerably lower than fear responses evoked by stimulation of the central nucleus of the amygdala (CeA) (reviewed in ref. 27), suggesting that the CeA is more directly connected with the behavioral output pathways responsible for fear responses.”
What the sources say
- Not checked yetcites [27] Davis M. The role of the amygdala in conditioned and unconditioned fear and anxiety. In: Aggleton JP, editor. The Amygdala. 2nd Ed. Oxford: Oxford Univ Press; 2000. pp. 213–288. [Google Scholar] source
plaindirect- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“A large number of studies have provided convincing evidence that associative plasticity in the LA contributes to fear memory formation (4, 6, 7).”
What the sources say
- Not checked yetcites [4] Sah P, Westbrook RF, Lüthi A. Fear conditioning and long-term potentiation in the amygdala: What really is the connection? Ann N Y Acad Sci. 2008;1129:88–95. doi: 10.1196/annals.1417.020. [DOI] [PubMed] [Google Scholar] source
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- Not checked yetcites [7] Maren S, Quirk GJ. Neuronal signalling of fear memory. Nat Rev Neurosci. 2004;5:844–852. doi: 10.1038/nrn1535. [DOI] [PubMed] [Google Scholar] source
boosteddirect- Asserted: passes — The authors put it forward as true.
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Probably not a substantial claim.
None of the sources cited for this claim have been checked yet.
In the paper
“Fear conditioning is a simple form of associative learning that provides a powerful model system to study associative plasticity and memory formation (1–4).”
What the sources say
- Not checked yetcites [1] LeDoux JE. Emotion circuits in the brain. Annu Rev Neurosci. 2000;23:155–184. doi: 10.1146/annurev.neuro.23.1.155. [DOI] [PubMed] [Google Scholar] source
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plain- Asserted: passes — The authors put it forward as true.
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Probably not a substantial claim. It may be too vague to check against evidence. 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
“It is widely believed that LA plasticity underlying fear learning occurs as a result of a Hebbian mechanism whereby the shock US directly depolarizes LA pyramidal cells that are concurrently activated by weaker CS inputs, resulting in potentiation of the CS input synapses (5, 6, 9, 31).”
What the sources say
- Not checked yetcites [5] Rogan MT, Weisskopf MG, Huang YY, Kandel ER, LeDoux JE. Long term potentiation in the amygdala: Implications for memory formation. In: Holscher C, editor. Neuronal Mechanisms of Memory Formation. Cambridge, UK: Cambridge Univ Press; 2000. pp. 58–76. [Google Scholar] source
- Not checked yetcites [6] Blair HT, Schafe GE, Bauer EP, Rodrigues SM, LeDoux JE. Synaptic plasticity in the lateral amygdala: A cellular hypothesis of fear conditioning. Learn Mem. 2001;8:229–242. doi: 10.1101/lm.30901. [DOI] [PubMed] [Google Scholar] source
- Not checked yetcites [9] Rosenkranz JA, Grace AA. Dopamine-mediated modulation of odour-evoked amygdala potentials during pavlovian conditioning. Nature. 2002;417:282–287. doi: 10.1038/417282a. [DOI] [PubMed] [Google Scholar] source
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hedgeddirect- Asserted: fails — The authors may not put it forward as true.
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Probably not a substantial claim. The authors may not put it forward as true.
None of the sources cited for this claim have been checked yet.
In the paper
“The light activated channelrhodopsin (ChR2) (19, 20) has been used in other neural systems to activate specific cell populations and produce learning (21–23).”
What the sources say
- Not checked yetcites [21] Tsai HC, et al. Phasic firing in dopaminergic neurons is sufficient for behavioral conditioning. Science. 2009;324:1080–1084. doi: 10.1126/science.1168878. [DOI] [PMC free article] [PubMed] [Google Scholar] source
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plaindirect- Asserted: passes — The authors put it forward as true.
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Probably not a substantial claim. The paper’s conclusions may not depend on it.
None of the sources cited for this claim have been checked yet.
In the paper
“The lateral nucleus of the amygdala (LA) is a site of associative plasticity, where US-evoked depolarization of LA pyramidal neurons is thought to instruct plasticity at synapses formed by CS inputs onto the same neurons (5–7).”
What the sources say
- Not checked yetcites [5] Rogan MT, Weisskopf MG, Huang YY, Kandel ER, LeDoux JE. Long term potentiation in the amygdala: Implications for memory formation. In: Holscher C, editor. Neuronal Mechanisms of Memory Formation. Cambridge, UK: Cambridge Univ Press; 2000. pp. 58–76. [Google Scholar] source
- Not checked yetcites [6] Blair HT, Schafe GE, Bauer EP, Rodrigues SM, LeDoux JE. Synaptic plasticity in the lateral amygdala: A cellular hypothesis of fear conditioning. Learn Mem. 2001;8:229–242. doi: 10.1101/lm.30901. [DOI] [PubMed] [Google Scholar] source
- Not checked yetcites [7] Maren S, Quirk GJ. Neuronal signalling of fear memory. Nat Rev Neurosci. 2004;5:844–852. doi: 10.1038/nrn1535. [DOI] [PubMed] [Google Scholar] source
hedgedconditional- Asserted: passes — The authors put it forward as true.
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Probably not a substantial claim. 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
“This model suggests that depolarization of LA pyramidal cells by the US provides an instructive signal for LA plasticity and fear learning.”
hedgeddirect- Asserted: fails — The authors may not put it forward as true.
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Probably not a substantial claim. The authors may not put it forward as true. The paper may give no reason why it holds.
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In the paper
“In addition to being essential for aversively motivated learning, plasticity in the LA is also required for several forms of appetitively motivated learning (43–45) and a number of studies have found that separate populations of amygdala neurons mediate aversive and appetitive processing (46–48).”
What the sources say
- Not checked yetcites [43] Burns LH, Everitt BJ, Robbins TW. Intra-amygdala infusion of the N-methyl-D-aspartate receptor antagonist AP5 impairs acquisition but not performance of discriminated approach to an appetitive CS. Behav Neural Biol. 1994;61:242–250. doi: 10.1016/s0163-1047(05)80007-x. [DOI] [PubMed] [Google Scholar] source
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plaindirect- Asserted: passes — The authors put it forward as true.
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Probably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“Finally, this process is associative (i.e., requires the close temporal contiguity of the CS and laser US and that the laser US occurrence is contingent upon the CS preceding it, ref. 26) as it does not occur when the CS and the light US are temporally unpaired during training in ChR2-treated animals.”
What the sources say
- Not checked yetcites [26] Rescorla RA. Probability of shock in the presence and absence of CS in fear conditioning. J Comp Physiol Psychol. 1968;66:1–5. doi: 10.1037/h0025984. [DOI] [PubMed] [Google Scholar] source
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“A rater who was blind with respect to the treatment group scored animals’ behavioral freezing during the first 18 s of the CS (during the training phase) and during all of the 20 CS (during “testing”) offline using a digital stopwatch.”
plain- Asserted: passes — The authors put it forward as true.
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In the paper
“A fiber optic cable, which had been threaded through a polyethylene tether (Plastics One) and then through the tip of a stainless steel tube (26 g, Plastics One), was inserted into the chronic guide cannula on the animal's head by an experimenter who was blind as to what treatment the animals would receive.”
plain- Asserted: passes — The authors put it forward as true.
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In the paper
“Three ChR2/paired and 2 ChR2/unpaired were not included in the final analysis as these criteria were not met.”
plain- Asserted: passes — The authors put it forward as true.
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Probably not a substantial claim. The paper’s conclusions may not depend on it.
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In the paper
“Single neuron waveforms were then isolated offline and had to exhibit a refractory period of at least 1 ms and mean spike amplitude of at least 80 μV to be included in the study.”
plain- Asserted: passes — The authors put it forward as true.
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Probably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“In fact it has been suggested that coactivation of noradrenergic β receptors and subsequent G protein-coupled signaling pathways in conjunction with depolarization of LA neurons cooperatively regulates LA plasticity and fear conditioning (50).”
What the sources say
- Not checked yetcites [50] Bailey CH, Giustetto M, Huang YY, Hawkins RD, Kandel ER. Is heterosynaptic modulation essential for stabilizing Hebbian plasticity and memory? Nat Rev Neurosci. 2000;1:11–20. doi: 10.1038/35036191. [DOI] [PubMed] [Google Scholar] source
hedgeddirect- Asserted: fails — The authors may not put it forward as true.
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Probably not a substantial claim. The authors may not put it forward as true. The paper’s conclusions may not depend on it.
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In the paper
“Experimenters were blind as to what virus (AAV-CaMKII-ChR2/EYFP or AAV-CaMKII-GFP) was being injected.”
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
“All procedures were approved by the New York University Animal Care and Use Committee and conducted in accordance with the National Institutes of Health Guide for the Care and Use of Experimental Animals.”
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. 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
“For behavioral experiments, sections were processed as described above and an experimenter blind as to animal and treatment group assessed whether ChR2 was expressed in the LA neurons and whether the tip of the guide cannula was dorsal and proximal to the LA.”
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.
Probably not a substantial claim. It may state two separate claims as one.
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?
In the citing paper
“Briefly, activation of lateral amygdala neurons induces unconditioned freezing70.”
From Resolving the neural circuits of anxiety (2015) · cites this paper as [70]
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
§ Materials and Methods
“with trial being defined as a 1-s stimulation period at 20 Hz, 50 Hz, or constant laser illumination”
§ Materials and Methods
“dividing by the number of 1-min stimulation trials for each cell”
Citations
Cites
LeDoux, J. E. (2000) · Annual Review of Neuroscience · doi:10.1146/annurev.neuro.23.1.155 · Cited by 8,444
Self-citationMillisecond-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-citationChannelrhodopsin-2, a directly light-gated cation-selective membrane channel
Nagel, G., Szellas, T., Huhn, W., Kateriya, S., Adeishvili, N., Berthold, P. R., Ollig, D., Hegemann, P., & Bamberg, E. (2003) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1936192100 · Cited by 2,730
THE AMYGDALA MODULATES THE CONSOLIDATION OF MEMORIES OF EMOTIONALLY AROUSING EXPERIENCES
McGaugh, J. L. (2004) · Annual Review of Neuroscience · doi:10.1146/annurev.neuro.27.070203.144157 · Cited by 2,296
The Neurobiology of Consolidations, Or, How Stable is the Engram?
Dudai, Y. (2004) · Annual Review of Psychology · doi:10.1146/annurev.psych.55.090902.142050 · Cited by 1,671
Neuronal signalling of fear memory
Maren, S., & Quirk, G. J. (2004) · Nature Reviews Neuroscience · doi:10.1038/nrn1535 · Cited by 1,428
Phasic Firing in Dopaminergic Neurons Is Sufficient for Behavioral Conditioning
Tsai, H.-C., Zhang, F., Adamantidis, A., Stuber, G. D., Bonci, A., de Lecea, L., & Deisseroth, K. (2009) · Science · doi:10.1126/science.1168878 · Cited by 1,266
Self-citationProbability of shock in the presence and absence of cs in fear conditioning.
Rescorla, R. A. (1968) · Journal of Comparative and Physiological Psychology · doi:10.1037/h0025984 · Cited by 1,067 · cited 1×
“, whether the learning was associative in nature) (26), another group of animals (ChR2/unpaired, n= 8) received random presentations of 16 CS and 16 laser-stimulation US, which were explicitly unpaired in time.”
MethodThe primate amygdala represents the positive and negative value of visual stimuli during learning
Paton, J. J., Belova, M. A., Morrison, S. E., & Salzman, C. D. (2006) · Nature · doi:10.1038/nature04490 · Cited by 917
Quirk, G. J., Repa, J. C., & LeDoux, J. E. (1995) · Neuron · doi:10.1016/0896-6273(95)90092-6 · Cited by 808
Self-citation
Cited by
Sorted by citations
Items 301–305 of 305
Peripersonal Space : hand-centred coding in perceptual and learning processes
Zanini, A. (2021) · theses.fr (ABES) · doi:10.70675/93b32e72z3792z4231z96ddz5621d33e348a
Neuronal mechanisms underlying contextual fear memory discrimination
Kim, H.-R. (2022) · theses.fr (ABES) · doi:10.70675/b6bffbc6zd1e1z4025za332za1476940d5da
Associative learning in Peripersonal Space: fear responses are acquired in hand-centered coordinatesPreprint
Brozzoli, C., Salemme, R., Farnè, A., & Zanini, A. (2025) · OSF Preprints (OSF Preprints)
Taugher, R. J., Chan, A. C., Kreple, C. J., Ghobbeh, A., Wang, G. Z., Harmata, G., Conlon, M. M., Gupta, S. C., Fan, R., Kuruba, R., et al. (2026) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.64898/2026.05.18.725939
AAV-Cre induces dose-dependent neurotoxicity and focal neuronal lesions
Giraudet, M., Cloarec, E., Gambino, F., & Augusto, E. (2026) · Scientific Reports · doi:10.1038/s41598-026-68031-6
Metadata
- Authors
- Johansen, J. P., Hamanaka, H., Monfils, M. H., Behnia, R., Deisseroth, K., Blair, H. T., & LeDoux, J. E.
- Affiliations
- New York University (US)
- Howard Hughes Medical Institute (US)
- University of California, Los Angeles (US)
- Nathan Kline Institute for Psychiatric Research (US)
- ORCID
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2010-06-25
- Volume
- 107
- Issue
- 28
- Pages
- 12692-12697
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC2906568
- OpenAlex
- W2090654839
- Semantic Scholar
- 0820aaefabf3c978a0c6e0954f97ebe130e1bb9f
- Cited by
- 308
- References
- 57
- Citations by year
- 2026: 3 · 2025: 8 · 2024: 21 · 2023: 11 · 2022: 8 · 2021: 21 · 2020: 22 · 2019: 21 · 2018: 14 · 2017: 20 · 2016: 21 · 2015: 35 · 2014: 28 · 2013: 32 · 2012: 23
- FWCI
- 14.51
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Howard Hughes Medical Institute
- Deutsches Krebsforschungszentrum
- York University
- National Institute of Mental Health (R01MH046516, F32MH082505)
- 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 › Neurobiology and Insect Physiology Research
- Keywords
- lateral amygdala, pyramidal neurons, fear conditioning, optogenetics, channelrhodopsin, auditory fear conditioning, aversive stimuli, fear memory, neuronal activity control
- MeSH terms
- Amygdala, Animals, Conditioning, Psychological, Conditioning, Classical, Cues, Fear, Male, Neurons, Phobic Disorders, Photic Stimulation, Rats, Sprague-Dawley, Pyramidal Cells, Rats
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 2026-10-09, under version 3 of the claim definition (model deepseek-v4.1-flash, prompt extract-v3).
A second model labelled each claim on 2026-10-09 (model jev-1.13-20260917, definition revision gold-guideline-v0.2).
Cited sources are checked with a language model’s help (gpt-6-sol).
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 ›
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