The DOI matches its Crossref record; 55 of the 55 references it cites were found in a registry or an index.
Genetic dissection of an amygdala microcircuit that gates conditioned fear
Open accessAbstract
The role of different amygdala nuclei (neuroanatomical subdivisions) in processing Pavlovian conditioned fear has been studied extensively, but the function of the heterogeneous neuronal subtypes within these nuclei remains poorly understood. Here we use molecular genetic approaches to map the functional connectivity of a subpopulation of GABA-containing neurons, located in the lateral subdivision of the central amygdala (CEl), which express protein kinase C-δ (PKC-δ). Channelrhodopsin-2-assisted circuit mapping in amygdala slices and cell-specific viral tracing indicate that PKC-δ(+) neurons inhibit output neurons in the medial central amygdala (CEm), and also make reciprocal inhibitory synapses with PKC-δ(-) neurons in CEl. Electrical silencing of PKC-δ(+) neurons in vivo suggests that they correspond to physiologically identified units that are inhibited by the conditioned stimulus, called CEl(off) units. This correspondence, together with behavioural data, defines an inhibitory microcircuit in CEl that gates CEm output to control the level of conditioned freezing.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
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
“The amygdala plays a key role in defensive behaviour and switching between defensive modes in rodents [39–42].”
From Freeze for action: neurobiological mechanisms in animal and human freezing (2017) · cites this paper as [42]
Experimental — accuracy not yet measuredIn the citing paper
“since BLA neurons excite GABAergic CeL neurons26 that provide feed-forward inhibition onto CeM “output” neurons6,18,19”
From Amygdala circuitry mediating reversible and bidirectional control of anxiety (2011) · cites this paper as [19]
In the citing paper
“For instance, a population of GABAergic neurons in the CeL which express protein kinase C-delta (PKC-delta+ neurons) increase their spontaneous activity following fear conditioning [34], and are involved in fear generalization and anxiety (Fig. 1D) [4].”
From An emerging circuit pharmacology of GABAA receptors (2018) · cites this paper as [34]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
LeDoux, J. E. (2000) · Annual Review of Neuroscience · doi:10.1146/annurev.neuro.23.1.155 · Cited by 8,444
Experimental Design in Psychological Research
(2002) · The MIT Press eBooks · doi:10.7551/mitpress/3080.003.0011 · Cited by 2,471
A gene expression atlas of the central nervous system based on bacterial artificial chromosomes
Gong, S., Zheng, C., Doughty, M. L., Losos, K., Didkovsky, N., Schambra, U. B., Nowak, N. J., Joyner, A., Leblanc, G., Hatten, M. E., et al. (2003) · Nature · doi:10.1038/nature02033 · Cited by 2,108
Regulation of parkinsonian motor behaviours by optogenetic control of basal ganglia circuitry
Kravitz, A. V., Freeze, B. S., Parker, P. R. L., Kay, K., Thwin, M. T., Deisseroth, K., & Kreitzer, A. C. (2010) · Nature · doi:10.1038/nature09159 · Cited by 1,885
Self-citationMultimodal fast optical interrogation of neural circuitry
Zhang, F., Wang, L., Brauner, M., Liewald, J. F., Kay, K., Watzke, N., Wood, P. G., Bamberg, E., Nagel, G., GOTTSCHALK, A. R., et al. (2007) · Nature · doi:10.1038/nature05744 · Cited by 1,766
Self-citationLeDoux, J., Iwata, J., Cicchetti, P., & Reis, D. (1988) · The Journal of Neuroscience · doi:10.1523/jneurosci.08-07-02517.1988 · Cited by 1,580
Neuronal signalling of fear memory
Maren, S., & Quirk, G. J. (2004) · Nature Reviews Neuroscience · doi:10.1038/nrn1535 · Cited by 1,428 · cited 1×
“To avoid masking of the consequences of the experimental manipulation by ceiling and floor effects, the number of training trials (3-6) was adjusted such that freezing levels averaged around 50 % in the genetic/viral control.”
MethodMonosynaptic Restriction of Transsynaptic Tracing from Single, Genetically Targeted Neurons
Wickersham, I. R., Lyon, D. C., Barnard, R. J. O., Mori, T., Finke, S., Conzelmann, K., Young, J. A. T., & Callaway, E. M. (2007) · Neuron · doi:10.1016/j.neuron.2007.01.033 · Cited by 1,176
Self-citationSzymczak, A. L., Workman, C. J., Wang, Y., Vignali, K. M., Dilioglou, S., Vanin, E. F., & Vignali, D. A. A. (2004) · Nature Biotechnology · doi:10.1038/nbt957 · Cited by 1,059
Targeting 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
Flagged first, then by citations
Cited by
Sorted by citations
Items 801–839 of 839
Hegoburu, C., Tang, Y., Niu, R., Ghosh, S., Río, R. T.-D., Salgado, I., Abatis, M., Caseiro, D. M., van den Burg, E. H., Grundschober, C., et al. (2023) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2023.10.29.563530
Impaired oxytocin signaling in the central amygdala in rats with chronic heart failurePreprint
Althammer, F., Roy, R. K., Kirchner, M. K., Campos‐Lira, E., Schimmer, S., Charlet, A., Grinevich, V., & Stern, J. E. (2023) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2023.11.22.568271
“The GABAergic microcircuit connecting the CeL to the CeM has garnered significance in the regulation of mood and memory 48,53-57 .”
BackgroundResultDifferential contribution of distinct neuronal populations to danger representationsPreprint
Menegolla, A. P., Lopez-Fernandez, G., Herry, C., & Martín‐Fernández, M. (2024) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2024.01.24.577067
(2018) · Cambridge University Press eBooks · doi:10.1017/9781108377485.012
Krisenhafte Veränderungen in Gehirn und Psyche
Brenner, M., & Durstewitz, D. (2024) · Der Nervenarzt · doi:10.1007/s00115-024-01770-x
Insights into the Neurobiology of Behavioral Inhibition from Nonhuman Primate Models
Campos, L., Drzewiecki, C. M., & Fox, A. S. (2024) · Current topics in behavioral neurosciences · doi:10.1007/7854_2024_561
Lamprecht, R. (2024) · Elsevier eBooks · doi:10.1016/b978-0-443-15754-7.00072-9
Lipshutz, A. B., Saltz, V., Anderson, K. R., Manganaro, A., & Dumitriu, D. (2025) · Frontiers in Molecular Neuroscience · doi:10.3389/fnmol.2025.1347539
Optogenetics and Related Technologies for Psychiatric Disease Research
Fenno, L. E., & Deisseroth, K. A. (2025) · Oxford University Press eBooks · doi:10.1093/med/9780197640654.003.0006
Self-citationLi, J., Li, Z., Tian, H.-M., Tao, S.-S., Zhang, Q., Li, F. Y., & Li, Y.-Q. (2025) · SSRN Electronic Journal · doi:10.2139/ssrn.5213674
Central role of regular firing neurons of centrolateral amygdala in affective behaviors
García, A., Aller, M. I., Paternain, A. V., & Lerma, J. (2025) · iScience · doi:10.1016/j.isci.2025.112649
“17,48,49 We have classified CeL amygdala neurons into two subgroups from a functional point of view.”
mWAKE in the Central Amygdala Regulates Fear Learning and Memory
Xiong, J., Mehta, A., Liu, Q., Luo, A. X., Li, P. P., Janak, P. H., & Wu, M. N. (2025) · Journal of Neuroscience · doi:10.1523/jneurosci.0225-25.2025
Bertotto, L. B., Sakoulas, E. M., Logrip, M. L., Lin, K., Pimentel, A. E., Thompson, L., Cruz, B., Vozella, V., Favoretto, C. A., Roberto, M., et al. (2025) · Neurobiology of Stress · doi:10.1016/j.ynstr.2025.100770
“…inhibitory somatostatin-negative CeL neurons (many that express protein kinase C δ , enkephalin, and/or corticotropin-releasing factor [CRF]) instead reduces freezing and promotes active fear responses ( e.g. , escape) (Fadok et al., 2017; Haubensak et al., 2010; Yan et al., 2019; Yu et al., 2016).”
Additional file 3 of Experience-dependent changes in affective valence of taste in male mice
Hamada, S., Mikami, K., Ueda, S., Nagase, M., Nagashima, T., Yamamoto, M., Bito, H., Takemoto‐Kimura, S., Ohtsuka, T., & Watabe, A. M. (2023) · Figshare · doi:10.6084/m9.figshare.22621613
Dorsal Raphe VIP Neurons Are Critical for Survival‐Oriented Vigilance
Guillaumin, A., Perrot, E., Dhellemmes, T., Boi, L., Medeiros, D. D. C., Glangetas, C., Dumas, S., Doveró, S., Biendon, N., Ladevèze, E., et al. (2026) · Advanced Science · doi:10.1002/advs.202523809
“They also contain neurons expressing Protein Kinase C delta (PKC-δ ), a marker critical for emotional processing and the modulation of defensive behaviors based on the proximity of a threat [ 34–36 ].”
Gashi, L., Lubec, J., Daneyshar, B. H., Steinkellner, T., & Khom, S. (2026) · Neuropharmacology · doi:10.1016/j.neuropharm.2026.110927
Zhang, L., Hernández, V. S., Giraldo‐Gómez, D. M., Jiang, S. Z., León‐Contreras, J. C., Ye, R., Zhang, S., Schäfer, M., Barrio, R. A., Hernández‐Pando, R., et al. (2026) · PNAS Nexus · doi:10.1093/pnasnexus/pgag083 · Cited by 4
“Within the EA, PKC δ + /GABAergic neurons in CeL/CeC inhibit GABAergic output neurons in medial CeA (CeM), establishing a local disinhibition motif that gates downstream autonomic pathways (39).”
The neural circuitry of fear conditioning : a theoretical account
Angelhuber, M. (2016) · theses.fr (ABES) · doi:10.70675/df1f8188z8908z4025zaa82z92507ac9751b
Studying Neuronal Connectivity in the Mouse Brain in Normal Condition and Fragile X Syndrome
Haberl, M. G. (2014) · theses.fr (ABES) · doi:10.70675/cbb47168z82fbz41a1z9174zd9e36b2b5a6d
Ye, J. (2018) · theses.fr (ABES) · doi:10.70675/7d321ecaza13fz4852z82eaz45263b2adf7b
“, 2010) ; elles forment dans le CeA des circuits inhibiteurs locaux spécifiques (Haubensak et al., 2010; Li et al., 2013) et sont à l'origine des projections longues (Cai et al.”
BackgroundInfluentialCircuits neuronaux sous-tendant la régulation émotionnelle par le système ocytocinergique
Goyon, S. (2018) · theses.fr (ABES) · doi:10.70675/c8c9bec0z7b79z4826z862az93b128e1ada6
Douceau, S. (2020) · theses.fr (ABES) · doi:10.70675/6f1007f2z8468z4365zb07dz7d863bf32cd5
Role of medial prefrontal cortex long-range somatostatin inhibitory projections in fear behaviour
Aincy, M. (2020) · theses.fr (ABES) · doi:10.70675/cbf14899z34dcz4fd4z8c52zb2c8952c187f
Functional identification of GluN3A subunit-containing NMDA receptors in the adult brain
Gerges, S. A. (2020) · theses.fr (ABES) · doi:10.70675/396af5c3z01b5z4f37z8e98zd597406fe5ab
Neuronal mechanisms underlying contextual fear memory discrimination
Kim, H.-R. (2022) · theses.fr (ABES) · doi:10.70675/b6bffbc6zd1e1z4025za332za1476940d5da
The central amygdala integrates exogenous glucagon-like peptide 1 signalsPreprint
Duran, M., Zeng, N., Cutts, E. J., Habegger, K. M., & Hardaway, J. A. (2026) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.64898/2026.04.06.716705
Neuronal basis of decision-making under opposed valence affective states
Azraoui, A. E. (2024) · theses.fr (ABES) · doi:10.70675/deeb43a5z6accz4998z8619z6a33d6f4be8e
Hines, R. C., O’Sullivan-Duffy, A., & Sheets, P. L. (2026) · Neuropharmacology · doi:10.1016/j.neuropharm.2026.110967
Sizer, S. E., Brown, A. R., Anderson, J. K., Summerlin, A. E., Girgis, I., Yang, S. Y., Bedard, M. L., Olson, S. H., Slosky, L. M., Leinninger, G. M., et al. (2026) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.64898/2026.04.30.722083
“The bed nucleus of the stria terminalis (BNST) is another component of the extended amygdala and is homologous to the CeA with similarities in GABAergic cellular composition, protein and neuropeptide expression, and afferent and efferent projections [35 – 37].”
The lateralized locus coeruleus as a switch between direct and vicarious fear
Kim, J.-H., & Shin, H. (2026) · Cell Signaling · doi:10.46439/signaling.4.084
Sizer, S. E., Brown, A. R., Anderson, J. K., Summerlin, A. E., Girgis, I., Yang, S. Y., Bedard, M. L., Olson, S. H., Slosky, L. M., Leinninger, G. M., et al. (2026) · Addiction Neuroscience · doi:10.1016/j.addicn.2026.100285
A hypothalamic neuronal population coordinates metabolic adaptations to cold
Liu, H., Liu, Q., Bean, J. C., Wang, F., Jian, J., Li, Y., Conde, K., Wang, M., Deng, Y., Yang, Y., et al. (2026) · Neuron · doi:10.1016/j.neuron.2026.08.024
Cannabinoid modulation of central amygdala population dynamics during threat investigation
Yasmin, F., Naskar, S., Zaidi, D., Kandil, I. F., Kwon, M., Rosas-Vidal, L. E., & Patel, S. (2026) · Nature Communications · doi:10.1038/s41467-026-77957-4
“Speci fi cally, cannabinoids increase Fos protein expression in the CeA 23 – 25 , a key neural substrate for anxiety, emotional learning, and stress-reactivity 26 – 30 .”
Developmental trajectories organize the assembly of valence circuits in the central amygdalaPreprint
He, S., de Almeida, A. P., Feng, C., Petkovic, A., Tamais, A. M., Pospelova, A., Mayer, C., & Klein, R. (2026) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.64898/2026.10.18.759923
Zhang, Y.-Y., Hu, M.-T., Xie, S., Yu, C.-X., Xu, Y.-H., Chen, X., Tang, M., Li, C., Zhu, Y., Hu, J.-X., et al. (2026) · Neuron · doi:10.1016/j.neuron.2026.09.032
Metadata
- Authors
- Haubensak, W., Kunwar, P. S., Cai, H., Ciocchi, S., Wall, N. R., Ponnusamy, R., Biag, J., Dong, H.-W., Deisseroth, K., Callaway, E. M., Fanselow, M. S., Lüthi, A., & Anderson, D. J.
- Affiliations
- California Institute of Technology (US)
- Salk Institute for Biological Studies (US)
- University of California, Los Angeles (US)
- Stanford University (US)
- Friedrich Miescher Institute (CH)
- Corresponding author
- Anderson, David J.
- ORCID
- Venue
- Nature
- Published
- 2010-11
- Volume
- 468
- Issue
- 7321
- Pages
- 270-276
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- PMC
- PMC3597095
- OpenAlex
- W1981044491
- Cited by
- 840
- References
- 55
- Citations by year
- 2026: 24 · 2025: 35 · 2024: 50 · 2023: 45 · 2022: 64 · 2021: 62 · 2020: 50 · 2019: 55 · 2018: 84 · 2017: 51 · 2016: 50 · 2015: 68 · 2014: 50 · 2013: 58 · 2012: 46
- FWCI
- 29.09
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- CaltechAUTHORS (California Institute of Technology) (submittedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- Funders
- Howard Hughes Medical Institute
- National Institute of Mental Health (R01MH063912, R01MH085082)
- National Institute of Neurological Disorders and Stroke (RC2NS069464)
- 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
- central amygdala, fear conditioning, protein kinase C delta, GABAergic neurons, inhibitory microcircuits, disinhibition, conditioned freezing, fear memory, neuronal cell types
- MeSH terms
- Amygdala, Animals, Axonal Transport, Cells, Cultured, Conditioning, Classical, Fear, Female, gamma-Aminobutyric Acid, Genetic Techniques, Humans, Male, Mice, Transgenic, Neural Inhibition, Neural Pathways, Neurons, Synapses, Freezing Reaction, Cataleptic, Mice, Protein Kinase C-delta
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.
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
