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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.
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“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]
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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
Cited by
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Items 301–400 of 839
Optogenetic approaches for functional mouse brain mapping
Lim, D. H., LeDue, J. M., Mohajerani, M. H., Vanni, M. P., & Murphy, T. H. (2013) · Frontiers in Neuroscience · doi:10.3389/fnins.2013.00054 · Cited by 49
“ChR2-assisted circuit mapping (CRACM) combines photostimulation of multiple points in the sample with postsynaptic recording to investigate cortical circuits in brain slices (Petreanu et al., 2007, 2009; Atasoy et al., 2008; Haubensak et al., 2010).”
BackgroundCellular, circuit and transcriptional framework for modulation of itch in the central amygdala
Samineni, V. K., Grajales‐Reyes, J. G., Grajales‐Reyes, G. E., Tycksen, E., Copits, B. A., Pedersen, C. E., Ankudey, E. S., Sackey, J. N., Sewell, S. B., Bruchas, M. R., et al. (2021) · eLife · doi:10.7554/elife.68130 · Cited by 54
Neuronal basis for pain-like and anxiety-like behaviors in the central nucleus of the amygdala
Chen, W., Lien, C., & Chen, C. (2021) · Pain · doi:10.1097/j.pain.0000000000002389 · Cited by 49
Zhang, Z., Tao, W., Hou, Y.-Y., Wang, W., Lu, Y.-G., & Pan, Z. Z. (2014) · Neuropsychopharmacology · doi:10.1038/npp.2014.77 · Cited by 49
“CeA consists of 95% GABAergic neurons (Ehrlich et al, 2009; Haubensak et al, 2010).”
The mouse genetics toolkit: revealing function and mechanism
van der Weyden, L., White, J. K., Adams, D. J., & Logan, D. W. (2011) · Genome biology · doi:10.1186/gb-2011-12-6-224 · Cited by 49
miR-135a Regulates Synaptic Transmission and Anxiety-Like Behavior in Amygdala
Mannironi, C., Biundo, A., Rajendran, S., De Vito, F., Saba, L., Caioli, S., Zona, C., Ciotti, T., Caristi, S., Perlas, E., et al. (2018) · Molecular Neurobiology · doi:10.1007/s12035-017-0564-9 · Cited by 49
Acevedo, M. B., Fabio, M. C., Fernández, M. S., & Pautassi, R. M. (2016) · Neuroscience · doi:10.1016/j.neuroscience.2016.08.011 · Cited by 48
Fetterly, T. L., Basu, A., Nabit, B. P., Awad, E. K., Williford, K. M., Centanni, S. W., Matthews, R. T., Silberman, Y., & Winder, D. G. (2018) · Journal of Neuroscience · doi:10.1523/jneurosci.1035-18.2018 · Cited by 50
“Previous studies in the CeA have suggested that 2A-ARs decrease PBN release probability by directly interacting with the release machinery (Delaney et al., 2007).”
BackgroundInfluentialFu, J., Yu, X.-D., Zhu, Y., Xie, S., Tang, M., Yu, B., & Li, X. (2020) · Neuroscience Bulletin · doi:10.1007/s12264-020-00545-z · Cited by 49
Visser, R. M., Bathelt, J., Scholte, H. S., & Kindt, M. (2021) · Journal of Neuroscience · doi:10.1523/jneurosci.0857-21.2021 · Cited by 53
“, compared with local field potentials) may be insufficient to study structures like the amygdala, which includes nuclei with dissociable and even opposite function (Swanson and Petrovich, 1998; Reijmers et al., 2007; Quirk and Mueller, 2008; Ciocchi et al., 2010; Haubensak et al., 2010; Orsini and Maren, 2012).”
BackgroundAmano, T., Amir, A., Goswami, S., & Paré, D. (2012) · Journal of Neurophysiology · doi:10.1152/jn.00514.2012 · Cited by 46
May, T., Ozden, I., Brush, B. R., Borton, D. A., Wagner, F. B., Agha, N. S., Sheinberg, D. L., & Nurmikko, A. V. (2014) · PLoS ONE · doi:10.1371/journal.pone.0114529 · Cited by 47
“for studying neural mechanisms of specific neurological diseases [23, 25–28] and information processing at the microcircuit level in the brain [27, 29–35].”
BackgroundProjections from Infralimbic Cortex to Paraventricular Thalamus Mediate Fear Extinction Retrieval
Tao, Y., Cai, C.-Y., Xian, J.-Y., Kou, X., Lin, Y., Qin, C., Wu, H., Chang, L., Luo, C., & Zhu, D. (2020) · Neuroscience Bulletin · doi:10.1007/s12264-020-00603-6 · Cited by 48
Cell-type specific changes in PKC-delta neurons of the central amygdala during alcohol withdrawal
Dilly, G. A., Kittleman, C. W., Kerr, T. M., Messing, R. O., & Mayfield, R. D. (2022) · Translational Psychiatry · doi:10.1038/s41398-022-02063-0 · Cited by 47
“PKCδ neurons are associated with negatively valenced stimuli and fear learning [5, 50].”
BackgroundSiuda, E. R., Al‐Hasani, R., McCall, J. G., Bhatti, D. L., & Bruchas, M. R. (2016) · Neuropsychopharmacology · doi:10.1038/npp.2015.371 · Cited by 50
“The CeA is known to mediate conditioned fear and the acquisition of fear conditioning via inhibitory circuitry (Ciocchi et al, 2010; Haubensak et al, 2010; Wilensky et al, 2006).”
BackgroundMcCullough, K. M., Morrison, F. G., & Ressler, K. J. (2016) · Neurobiology of Learning and Memory · doi:10.1016/j.nlm.2016.07.025 · Cited by 50
“circuitry underlying fear conditioning behavior (Ciocchi et al., 2010; Haubensak et al., 2010).”
BackgroundMethodInfluentialCommon Biological Mechanisms of Alcohol Use Disorder and Post-Traumatic Stress Disorder
Suh, J. (2018) · Alcohol research · doi:10.35946/arcr.v39.2.04 · Cited by 46
Neural circuits for coping with social defeat
Diaz, V. E., & Lin, D. (2019) · Current Opinion in Neurobiology · doi:10.1016/j.conb.2019.11.016 · Cited by 48
Stafford, J. M., Maughan, D. K., Ilioi, E. C., & Lattal, K. M. (2013) · Learning & Memory · doi:10.1101/lm.029801.112 · Cited by 47
“…specificity of these microcircuits as the cell-type (PKCd+/2; glutamate/GABAergic receptor subtypes) and the precise afferents/efferents of these amygdala subregions are critically important in regulating fear expression and extinction (Ciocchi et al. 2010; Haubensak et al. 2010; Dobi et al. 2013).”
BackgroundThe Insula Cortex Contacts Distinct Output Streams of the Central Amygdala
Ponserre, M., Peters, C., Fermani, F., Conzelmann, K., & Klein, R. (2020) · Journal of Neuroscience · doi:10.1523/jneurosci.0567-20.2020 · Cited by 45
“Previous studies have substantially extended our knowledge of differential inputs and outputs to molecularly defined CeA populations (Haubensak et al., 2010; Cai et al., 2014; Penzo et al., 2015; Douglass et al., 2017; Fadok et al., 2017; Kim et al., 2017; Schiff et al., 2018).”
BackgroundResultInfluentialModulation of the extinction of fear learning
Myskiw, J. D. C., Izquierdo, I., & Furini, C. R. G. (2014) · Brain Research Bulletin · doi:10.1016/j.brainresbull.2014.04.006 · Cited by 44
Dedic, N., Kühne, C., Gomes, K. S., Hartmann, J., Ressler, K. J., Schmidt, M. V., & Deussing, J. M. (2019) · Frontiers in Neuroscience · doi:10.3389/fnins.2019.00986 · Cited by 46
“In view of CRH’s important role in conditioned fear (Haubensak et al., 2010; Isogawa et al., 2013; Tovote et al., 2015; Sanford et al., 2016; Fadok et al., 2017; Dedic et al., 2018a), we additionally assessed auditory and contextual fear memory.”
BackgroundHerman, M. A., Varodayan, F. P., Oleata, C. S., Luu, G., Kirson, D., Heilig, M. A., Ciccocioppo, R., & Roberto, M. (2015) · Neuropharmacology · doi:10.1016/j.neuropharm.2015.10.027 · Cited by 44
“Intracellular recording of evoked responses We recorded from 84 CeA neurons (from the medial subdivision of the CeA) with sharp micropipettes filled with 3M KCl using discontinuous current-clamp mode (Cruz et al., 2012; Haubensak et al., 2010; Kallupi et al., 2014; Roberto et al., 2004a).”
The Legacy of the Benzodiazepine Receptor
Möhler, H. (2014) · Advances in pharmacology · doi:10.1016/bs.apha.2014.10.008 · Cited by 43
Alcohol Dependence Disrupts Amygdalar L-Type Voltage-Gated Calcium Channel Mechanisms
Varodayan, F. P., de Guglielmo, G., Logrip, M. L., George, O., & Roberto, M. (2017) · Journal of Neuroscience · doi:10.1523/jneurosci.3721-16.2017 · Cited by 42
“As the CeA comprises a highly interconnected network of GABA interneurons and GABA projection neurons (Lopez de Armentia and Sah, 2004; Haubensak et al., 2010; Marek et al., 2013), alcohol enhancement of firing in a restricted neuronal population will most likely increase GABA release onto a large number of CeA neuron…”
BackgroundInfluentialAndraka, K., Kondrakiewicz, K., Rojek-Sito, K., Ziegart-Sadowska, K., Meyza, K. Z., Nikolaev, T., Hamed, A., Kursa, M. B., Wójcik, M., Danielewski, K., et al. (2021) · Current Biology · doi:10.1016/j.cub.2021.03.047 · Cited by 46
Yu, H., Chen, L., Lei, H., Pi, G., Xiong, R., Jiang, T., Wu, D., Sun, F., Gao, Y., Li, Y., et al. (2022) · Nature Communications · doi:10.1038/s41467-022-33139-6 · Cited by 46
Mouse models of fear-related disorders: Cell-type-specific manipulations in amygdala
Gafford, G. M., & Ressler, K. J. (2015) · Neuroscience · doi:10.1016/j.neuroscience.2015.06.019 · Cited by 46
“GABA-producing inhibitory neurons gate expression of fear via tonic inhibition of the CeM (19-23) and go on to effect downstream structures such as the periaqueductal grey (PAG), locus coeruleus (LC) and parabrachial nuclei (PB) that direct behavioral output (6).”
InfluentialPrefrontal dopamine regulates fear reinstatement through the downregulation of extinction circuits
HitoraーImamura, N., Miura, Y., Teshirogi, C., Ikegaya, Y., Matsuki, N., & Nomura, H. (2015) · eLife · doi:10.7554/elife.08274 · Cited by 43
“…from the IL and contains two functionally distinct subpopulations of neurons (CElon or somatostatin-expressing neurons, and CEloff or protein kinase C-δ-expressing neurons) forming local inhibitory circuits to inhibit CeM activity (Ciocchi et al., 2010; Haubensak et al., 2010; Li et al., 2013).”
Molecular and Cellular Effects of Traumatic Stress: Implications for PTSD
Girgenti, M. J., Hare, B. D., Ghosal, S., & Duman, R. S. (2017) · Current Psychiatry Reports · doi:10.1007/s11920-017-0841-3 · Cited by 45
McCullough, K. M., Daskalakis, N. P., Gafford, G. M., Morrison, F. G., & Ressler, K. J. (2018) · Translational Psychiatry · doi:10.1038/s41398-018-0190-y · Cited by 40
Γ-Aminobutyric acid in adult brain: an update
Siucińska, E. (2019) · Behavioural Brain Research · doi:10.1016/j.bbr.2019.112224 · Cited by 43
Emerging role of astrocytes in oxytocin-mediated control of neural circuits and brain functions
Baudon, A., Creusot, E. C., Althammer, F., Schaaf, C. P., & Charlet, A. (2022) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2022.102328 · Cited by 44
“with the fear-OFF function of those cells (Haubensak et al., 2010).”
BackgroundImpact of infralimbic inputs on intercalated amygdala neurons: A biophysical modeling studyPreprint
Li, G., Amano, T., Paré, D., & Nair, S. S. (2011) · Learning & Memory · doi:10.1101/lm.1938011 · Cited by 47
“Moreover, after fear conditioning, CS presentations inhibited PKC-d expressing CeL cells (hereafter termed CeL neurons) (Ciocchi et al. 2010; Haubensak et al. 2010), whereas PKC-dnegative CeL neurons were excited by the CS (hereafter termed CeL cells).”
BackgroundSimonetti, M., Paldy, E., Njoo, C., Bali, K. K., Worzfeld, T., Pitzer, C., Kuner, T., Offermanns, S., Mauceri, D., & Kuner, R. (2021) · Molecular Psychiatry · doi:10.1038/s41380-019-0491-4 · Cited by 41
Ecological analysis of Pavlovian fear conditioning in rats
Zambetti, P. R., Schuessler, B. P., Lecamp, B., Shin, A., Kim, E. J., & Kim, J. J. (2022) · Communications Biology · doi:10.1038/s42003-022-03802-1 · Cited by 44
Amygdala-Dependent Molecular Mechanisms of the Tac2 Pathway in Fear Learning
Andero, R., Daniel, S., Guo, J., Bruner, R. C., Seth, S., Marvar, P. J., Rainnie, D. G., & Ressler, K. J. (2016) · Neuropsychopharmacology · doi:10.1038/npp.2016.77 · Cited by 41
The Amygdala Noradrenergic System Is Compromised With Alcohol Use Disorder
Varodayan, F. P., Patel, R. R., Matzeu, A., Wolfe, S. A., Curley, D. E., Khom, S., Gandhi, P. J., Rodriguez, L., Bajo, M., D’Ambrosio, S. R., et al. (2022) · Biological Psychiatry · doi:10.1016/j.biopsych.2022.02.006 · Cited by 40
Neuronal cell types, projections, and spatial organization of the central amygdala
O’Leary, T. P., Kendrick, R. M., Bristow, B. N., Sullivan, K. E., Wang, L., Clements, J., Lemire, A. L., & Cembrowski, M. S. (2022) · iScience · doi:10.1016/j.isci.2022.105497 · Cited by 42
BNST PKCδ neurons are activated by specific aversive conditions to promote anxiety-like behavior
Williford, K. M., Taylor, A., Melchior, J. R., Yoon, H. J., Sale, E., Negasi, M. D., Adank, D. N., Brown, J. A., Bedenbaugh, M. N., Luchsinger, J. R., et al. (2023) · Neuropsychopharmacology · doi:10.1038/s41386-023-01569-5 · Cited by 38
“Some of the densest projections come from amygdalar subregions including the BLA, CeA, and BMA, which encode information about threat and the animal’s current emotional state [26, 46, 47, 65, 66], and we validated that both the BLA and CeA cells provide functional input to BNST cells.”
BackgroundParetkar, T., & Dimitrov, E. L. (2018) · Neurobiology of Disease · doi:10.1016/j.nbd.2018.12.005 · Cited by 41
“Approximately 40% of the PKC-δ neurons express Enk mRNA (Haubensak et al., 2010).”
BackgroundInfluentialButler, R. K., White, L. C., Frederick-Duus, D., Kaigler, K. F., Fadel, J. R., & Wilson, M. A. (2012) · Experimental Neurology · doi:10.1016/j.expneurol.2012.08.002 · Cited by 42
“Elegant optogenetic studies have shown that the microcircuitry of the amygdala, specifically in the BLA and CEA, involves neurons which produce different behavioral outputs especially those related to conditioned fear and fear extinction (Haubensak et al., 2010; Herry et al., 2008).”
BackgroundInfluentialBajo, M., Herman, M. A., Varodayan, F. P., Oleata, C. S., Madamba, S. G., Harris, R. A., Blednov, Y. A., & Roberto, M. (2014) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2014.11.011 · Cited by 39
“We recorded from the medial subdivision of the CeA with sharp micropipettes filled with 3 M KCl using bridge current-clampmode (Cruz et al., 2012; Haubensak et al., 2010; Roberto et al., 2004).”
MethodHomeostatic regulation of memory systems and adaptive decisions
Mizumori, S. J. Y., & Jo, Y. S. (2013) · Hippocampus · doi:10.1002/hipo.22176 · Cited by 43
Neuropeptide signalling in the central nucleus of the amygdala
van den Burg, E. H., & Stoop, R. (2018) · Cell and Tissue Research · doi:10.1007/s00441-018-2862-6 · Cited by 42
Optogenetic Long-Term Depression Induction in the PVT-CeL Circuitry Mediates Decreased Fear Memory
Chen, M., & Bi, L. (2018) · Molecular Neurobiology · doi:10.1007/s12035-018-1407-z · Cited by 45
Sun, Y., Qian, L., Xu, L., Hunt, S., & Sah, P. (2020) · Molecular Psychiatry · doi:10.1038/s41380-020-00894-1 · Cited by 41
AgRP neurons trigger long-term potentiation and facilitate food seeking
Wang, C., Zhou, W., He, Y., Yang, T., Xu, P., Yang, Y., Cai, X., Wang, J., Liu, H., Yu, M., et al. (2021) · Translational Psychiatry · doi:10.1038/s41398-020-01161-1 · Cited by 40
Mumphrey, M. B., Hao, Z., Townsend, R. L., Patterson, L. M., Münzberg, H., Morrison, C. D., Ye, J., & Berthoud, H. R. (2016) · International Journal of Obesity · doi:10.1038/ijo.2016.38 · Cited by 37
“Wu Q, Boyle MP, Palmiter RD. Loss of GABAergic signaling by AgRP neurons to the parabrachial nucleus leads to starvation.”
Serine Racemase and D-serine in the Amygdala Are Dynamically Involved in Fear Learning
Balu, D. T., Presti, K. T., Huang, C. C., Muszynski, K., Radzishevsky, I. S., Wolosker, H., Guffanti, G., Ressler, K. J., & Coyle, J. T. (2017) · Biological Psychiatry · doi:10.1016/j.biopsych.2017.08.012 · Cited by 38
“Protein kinase C delta (PKCδ) neurons are referred to as CeLOFF because they inhibit output CeM neurons (47).”
BackgroundInfluentialWalker, L. C. (2021) · Journal of Neurochemistry · doi:10.1111/jnc.15301 · Cited by 38
“CeC/CeL PKCδ+ cells are believed to tonically inhibit CeM outputs to the periaqueductal gray (Haubensak et al., 2010) and they are in turn tightly regulated by adjacent SST+ cells.”
BackgroundMethodInfluentialG gene-deficient single-round rabies viruses for neuronal circuit analysis
Ghanem, A., & Conzelmann, K. (2015) · Virus Research · doi:10.1016/j.virusres.2015.05.023 · Cited by 38
Silencing of amygdala circuits during sepsis prevents the development of anxiety-related behaviours
Bourhy, L., Mazeraud, A., Costa, L. H. A., Levy, J., Rei, D., Hecquet, E., Gabanyi, I., Bozza, F. A., Chrétien, F., Lledo, P.-M., et al. (2022) · Brain · doi:10.1093/brain/awab475 · Cited by 37
Yan, J., Ding, X., He, T., Chen, A.-X., Zhang, W., Yu, Z., Cheng, X., Wei, C.-Y., Hu, Q.-D., Liu, X.-Y., et al. (2022) · Nature Communications · doi:10.1038/s41467-022-35211-7 · Cited by 40
An active inference perspective for the amygdala complex
Sladky, R., Kargl, D., Haubensak, W. E., & Lamm, C. (2023) · Trends in Cognitive Sciences · doi:10.1016/j.tics.2023.11.004 · Cited by 41
“Signs of imminent danger (e.g., being jumped at) require rather in fl exible defense behaviors, such as freezing, startle, and fl inch responses, implemented by CeA – brainstem pathways [43].”
Self-citationSladky, R., Geissberger, N., Pfabigan, D. M., Kraus, C., Tik, M., Woletz, M., Paul, K., Vanicek, T., Auer, B., Kranz, G. S., et al. (2017) · NeuroImage · doi:10.1016/j.neuroimage.2016.12.024 · Cited by 37
“Recent studies were able to uncover a microcircuit of GABA-erg neurons within CeA playing an important role in encoding and gating of fear responses towards conditioned stimuli (Ciocchi, 2010; Haubensak et al., 2010).”
Mapping effective connectivity of human amygdala subdivisions with intracranial stimulation
Sawada, M., Adolphs, R., Dlouhy, B. J., Jenison, R. L., Rhone, A. E., Kovach, C. K., Greenlee, J. D. W., Howard, M. A., & Oya, H. (2022) · Nature Communications · doi:10.1038/s41467-022-32644-y · Cited by 40
Pain-related cortico-limbic plasticity and opioid signaling
Neugebauer, V., Presto, P., Yakhnitsa, V., Antenucci, N., Mendoza, B., & Ji, G. (2023) · Neuropharmacology · doi:10.1016/j.neuropharm.2023.109510 · Cited by 38
Vicario, A., Mendoza, E., Abellán, A., Scharff, C., & Medina, L. M. (2016) · Brain Structure and Function · doi:10.1007/s00429-016-1229-6 · Cited by 36
“…amygdala are involved in inhibitory modulation of the activity of other EAce cells, including those projecting to pain control centers of the brainstem (such as the periaqueductal gray) (Haubensak et al. 2010; Li et al. 2013), and may be involved in stress-modulation of pain (Poulin et al. 2008).”
BackgroundBabij, R., Ferrer, C., Donatelle, A., Wacks, S., Buch, A. M., Niemeyer, J. E., Ma, H., Duan, Z. R. S., Fetcho, R. N., Che, A., et al. (2023) · Neuron · doi:10.1016/j.neuron.2022.10.037 · Cited by 35
Frazier, S. J., Cohen, B. N., & Lester, H. A. (2013) · Journal of Biological Chemistry · doi:10.1074/jbc.m112.423921 · Cited by 35
“0 has been used in conjunction with channelrhodopsin-2-mediated activation to define an inhibitorymicrocircuit within the amygdala involved in mouse fear conditioning (65) and to identify a hypothalamic locus responsible for male mouse aggression and its close neuroanatomical relationship to mating circuits (66).”
MethodPsychiatric Disorders - Trends and Developments
Uehara, T. (2011) · InTech eBooks · doi:10.5772/2330 · Cited by 36
Yamauchi, N., Takahashi, D., Sugimura, Y. K., Kato, F., Amano, T., & Minami, M. (2018) · European Journal of Neuroscience · doi:10.1111/ejn.14165 · Cited by 37
“Haubensak et al. (2010) demonstrated that protein kinase Cδ (PKCδ)- positive and PKCδ- negative neurons in the lateral CeA make reciprocal inhibitory synapses with each other and that PKCδ- positive neurons send inhibitory projections to output neurons in the CeM.”
BackgroundNonhuman Primate Models to Explore Mechanisms Underlying Early-Life Temperamental Anxiety
Kenwood, M. M., & Kalin, N. H. (2020) · Biological Psychiatry · doi:10.1016/j.biopsych.2020.08.028 · Cited by 35
“This simplified circuit diagram depicts general organizational principles that have been characterized in rodent models (58,90,91,96).”
BackgroundLimoges, A., Yarur, H. E., & Tejeda, H. A. (2022) · Frontiers in Systems Neuroscience · doi:10.3389/fnsys.2022.963691 · Cited by 35
“Furthermore, given the restriction of Dyn expression to largely PKCδ neurons, which are thought to be engaged during fear (Ciocchi et al., 2010; Haubensak et al., 2010), the Dyn/KOR system in the amygdala may regulate valence processing.”
BackgroundInfluentialFear signaling in the prelimbic-amygdala circuit: a computational modeling and recording study
Pendyam, S., Bravo-Rivera, C., Burgos-Robles, A., Sotres-Bayón, F., Quirk, G. J., & Nair, S. S. (2013) · Journal of Neurophysiology · doi:10.1152/jn.00961.2012 · Cited by 37
Cannabinoids: Revealing their complexity and role in central networks of fear and anxiety
Murkar, A., Koninck, J. D., & Merali, Z. (2021) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2021.09.002 · Cited by 35
Livneh, U., & Paz, R. (2012) · Journal of Neuroscience · doi:10.1523/jneurosci.0323-12.2012 · Cited by 36
“Studies in rodents use fear-conditioning paradigms as a model (Fanselow and Poulos, 2005), with a wealth of physiological methods to delineate the underlying circuitry for acquisition and expression of memories in the amygdala (Maren and Quirk, 2004; Ciocchi et al., 2010; Haubensak et al., 2010; Pape and Paré, 2010).”
BackgroundLight‐induced regulation of ligand‐gated channel activity
Bregestovski, P. D., Maleeva, G., & Gorostiza, P. (2017) · British Journal of Pharmacology · doi:10.1111/bph.14022 · Cited by 34
“, 2013), control the behaviour of organisms (Covington et al., 2010; Haubensak et al., 2010; Miesenböck, 2011) and find novel ways of treating certain diseases (Laprell et al.”
BackgroundWolfe, S. A., Sidhu, H., Patel, R. R., Kreifeldt, M., D’Ambrosio, S. R., Contet, C., & Roberto, M. (2019) · eNeuro · doi:10.1523/eneuro.0087-19.2019 · Cited by 36
“…medial (CeM) and lateral (CeL) subdivisions (Sun et al., 1991; Petrovich et al., 1996; Dong et al., 2001; Ciocchi et al., 2010; Davis et al., 2010; Haubensak et al., 2010; McCullough et al., 2018) and contains mostly GABAergic projection neurons and interneurons (Sun and Cassell, 1993; Veinante…”
BackgroundInfluentialTranslational neuroscience of basolateral amygdala lesions: Studies of urbach‐wiethe disease
Koen, N., Fourie, J., Terburg, D., Stoop, R., Morgan, B. E., Stein, D. J., & van Honk, J. (2016) · Journal of Neuroscience Research · doi:10.1002/jnr.23731 · Cited by 36
McCullough, K. M., Chatzinakos, C., Hartmann, J., Missig, G., Neve, R. L., Fenster, R. J., Carlezon, W. A., Daskalakis, N. P., & Ressler, K. J. (2020) · Nature Communications · doi:10.1038/s41467-020-18985-6 · Cited by 32
“Speci fi cally, within the CeL, three populations represent the majority of neurons: those marked by Crh, Sst , or Prkcd , 17,22,23,32 .”
Chemogenetics as a neuromodulatory approach to treating neuropsychiatric diseases and disorders
Song, J., Patel, R. V., Sharif, M. S., Ashokan, A., & Michaelides, M. (2021) · Molecular Therapy · doi:10.1016/j.ymthe.2021.11.019 · Cited by 33
Wang, L., Shen, M., Jiang, C., Ma, L., & Wang, F. (2016) · International Journal of Neuropsychopharmacology · doi:10.1093/ijnp/pyw060 · Cited by 29
“The complex interconnectivity of CeA, which plays prominent roles in fear and anxiety (Rodrigues et al., 2004; Ciocchi et al., 2010; Davis et al., 2010; Haubensak et al., 2010; Tye et al., 2011), has been discovered recently by the emerging optogenetic technique.”
BackgroundTinbergen’s challenge for the neuroscience of behavior
Pfaff, D. W., Tabansky, I., & Haubensak, W. E. (2019) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1903589116 · Cited by 33
Self-citationUnderstanding the heterogeneity of anxiety using a translational neuroscience approach
Drzewiecki, C. M., & Fox, A. S. (2024) · Cognitive Affective & Behavioral Neuroscience · doi:10.3758/s13415-024-01162-3 · Cited by 34
“…to induce different aspects of a threat response (Viviani et al., 2011); 3) neurons in CeL that project to CeM to induce threat responses (Haubensak et al., 2010); and 4) mutually inhibitory populations of CeL neurons that can elicit different threat responses when stimulated (i.e.,…”
BackgroundNew technologies for imaging synaptic partners
Wickersham, I. R., & Feinberg, E. H. (2012) · Current Opinion in Neurobiology · doi:10.1016/j.conb.2011.12.001 · Cited by 33
Optogenetic and chemogenetic insights into the food addiction hypothesis
Krashes, M. J., & Kravitz, A. V. (2014) · Frontiers in Behavioral Neuroscience · doi:10.3389/fnbeh.2014.00057 · Cited by 34
“…connection with a wide array of behaviors from those related to anxiety (Tye et al., 2011; Felix-Ortiz et al., 2013; Kim et al., 2013) or fear (Ciocchi et al., 2010; Haubensak et al., 2010; Johansen et al., 2010) as well as those related to reward-seeking (Stuber et al., 2010; Britt et al., 2012).”
BackgroundGrin1 Receptor Deletion within CRF Neurons Enhances Fear Memory
Gafford, G. M., Jasnow, A. M., & Ressler, K. J. (2014) · PLoS ONE · doi:10.1371/journal.pone.0111009 · Cited by 34
“Recent studies indicate fear conditioning changes the activity of CeA neurons in a CS-dependent manner [44–46], suggesting learning related changes are occurring within the CeA.”
BackgroundYu, Z., Swiercz, A. P., Moshfegh, C. M., Hopkins, L. S., Wiaderkiewicz, J., Speth, R. C., Park, J., & Marvar, P. J. (2019) · Biological Psychiatry · doi:10.1016/j.biopsych.2019.05.027 · Cited by 32
The Role of Oxytocin in Abnormal Brain Development: Effect on Glial Cells and Neuroinflammation
Knoop, M. S., Possovre, M.-L., Jacquens, A., Charlet, A., Baud, O., & Darbon, P. (2022) · Cells · doi:10.3390/cells11233899 · Cited by 35
“Notably, OTR expression has been found in more than half of this neuronal population [102,103].”
BackgroundTranscriptomics reveals amygdala neuron regulation by fasting and ghrelin thereby promoting feeding
Peters, C., He, S., Fermani, F., Lim, H., Ding, W., Mayer, C., & Klein, R. (2023) · Science Advances · doi:10.1126/sciadv.adf6521 · Cited by 29
Mazzitelli, M., Marshall, K., Pham, A., Ji, G., & Neugebauer, V. (2021) · Frontiers in Pharmacology · doi:10.3389/fphar.2021.668337 · Cited by 30
Jüngling, K., Lange, M. D., Szkudlarek, H. J., Lesting, J., Erdmann, F. S., Doengi, M., Kügler, S., & Pape, H. (2015) · Neuropsychopharmacology · doi:10.1038/npp.2015.125 · Cited by 32
“Importantly, fearon or fearoff neurons are characterized by the absence and presence of protein kinase C delta (PKCδ; Haubensak et al, 2010), and the majority of fear responsive neurons expresses the neuromodulatory peptide somatostatin (SOM; Li et al, 2013).”
BackgroundResultInfluentialPostweaning, forebrain-specific perturbation of the oxytocin system impairs fear conditioning
Pagani, J. H., Lee, H.-J., & Young, W. S. (2011) · Genes, Brain and Behavior · doi:10.1111/j.1601-183x.2011.00709.x · Cited by 30
“This is consistent with local inhibitory connections within the CeL and between the CeL and CeM that are crucial for plasticity related to conditioned fear (Ciocchi et al. 2010; Haubensak et al. 2010).”
BackgroundChemical genetics: receptor–ligand pairs for rapid manipulation of neuronal activity
Wulff, P., & Arenkiel, B. R. (2011) · Current Opinion in Neurobiology · doi:10.1016/j.conb.2011.10.008 · Cited by 33
“This silencing method has since been used in mice to investigate the roles of subtypes of GABAergic amygdala neurons in fear conditioning and hypothalamic neurons in aggression [30,31].”
PET Mapping of Neurofunctional Changes in a Posttraumatic Stress Disorder Model
Zhu, Y., Du, R., Zhu, Y., Shen, Y., Zhang, K., Chen, Y., Song, F., Wu, S., Zhang, H., & Tian, M. (2016) · Journal of Nuclear Medicine · doi:10.2967/jnumed.116.173443 · Cited by 31
“The posterior insular cortex projects strongly to GABAergic (GABA is g-aminobutyric acid) neurons in the lateral subdivision of central amygdala (CeL) in rats (19), which serves as a switch capable of orchestrating the activity of projection neurons in the medial subdivision of central amygdala (CeM) and consequently…”
BackgroundDaldrup, T., Lesting, J., Meuth, P., Seidenbecher, T., & Pape, H. (2016) · Neurobiology of Learning and Memory · doi:10.1016/j.nlm.2016.03.020 · Cited by 33
PACAP regulation of central amygdala GABAergic synapses is altered by restraint stress
Varodayan, F. P., Minnig, M. A., Steinman, M. Q., Oleata, C. S., Riley, M. W., Sabino, V., & Roberto, M. (2019) · Neuropharmacology · doi:10.1016/j.neuropharm.2019.107752 · Cited by 30
“The CeA is a primarily inhibitory nucleus, with an interconnected network of γ-aminobutyric acid (GABA) interneurons and GABA projection neurons that can inhibit each other via axon collaterals (Haubensak et al., 2010; Lopez de Armentia and Sah, 2004; Marek et al., 2013; Pape and Pare, 2010); the lateral (CeL) and cap…”
BackgroundOxytocin and Fear Memory Extinction: Possible Implications for the Therapy of Fear Disorders?
Baldi, E., Costa, A., Rani, B., Passani, M. B., Blandina, P., Romano, A., & Provensi, G. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms221810000 · Cited by 35
NPY Y2 receptors in the central amygdala reduce cued but not contextual fear
Verma, D., Wood, J. C., Lach, G., Mietzsch, M., Weger, S., Heilbronn, R., Herzog, H., Bonaventure, P., Sperk, G., & Tasan, R. O. (2015) · Neuropharmacology · doi:10.1016/j.neuropharm.2015.08.038 · Cited by 35
“The central nucleus of the amygdala (CEA), a pivotal component for fear expression, also harbors a highly elaboratedmicro-network capable of diverse types of plasticity (Ciocchi et al., 2010; Haubensak et al., 2010; Li et al., 2013; Wilensky et al., 2006).”
The Intrinsic Connectome of the Rat Amygdala
Schmitt, O., Eipert, P., Philipp, K., Kettlitz, R., Fuellen, G., & Wree, A. (2012) · Frontiers in Neural Circuits · doi:10.3389/fncir.2012.00081 · Cited by 31
“LA receives sensory inputs (Kim and Jung, 2006; Ciocchi et al., 2010; Haubensak et al., 2010; Tye and Deisseroth, 2012).”
BackgroundMedina, L. M., Abellán, A., Vicario, A., Castro‐Robles, B., & Desfilis, E. (2016) · Elsevier eBooks · doi:10.1016/b978-0-12-804042-3.00019-1 · Cited by 32
Baird, M. A., Hsu, T. Y., Wang, R., Juarez, B., & Zweifel, L. S. (2020) · eNeuro · doi:10.1523/eneuro.0370-20.2020 · Cited by 29
“It has also been shown that a proportion of CeL Oprk1-expressing neurons have overlapping expression with Pdyn (Bloodgood et al., 2020) and dynorphin co-localizes with SOM-expressing “fear on” neurons (Haubensak et al., 2010; Li et al., 2013; Kim et al., 2017; Ahrens et al., 2018).”
BackgroundInfluentialOptogenetics in psychiatric diseases
Touriño, C., Eban-Rothschild, A., & de Lecea, L. (2013) · Current Opinion in Neurobiology · doi:10.1016/j.conb.2013.03.007 · Cited by 30
“Decreased activity of CEl ‘off’ neurons disinhibits the CEm and induces freezing [39,40].”
BackgroundEgan, A. E., Seemiller, L. R., Packard, A. E. B., Solomon, M. B., & Ulrich‐Lai, Y. M. (2019) · Hormones and Behavior · doi:10.1016/j.yhbeh.2019.07.005 · Cited by 28
“The CeM is the main output nucleus of the CeA, and activation of this region is typically thought of as stressexcitatory (Beaulieu et al., 1986; Ciocchi et al., 2010; Duvarci et al., 2011; Feldman et al., 1994; Haubensak et al., 2010; Xu et al., 1999).”
BackgroundChemogenetics a robust approach to pharmacology and gene therapy
Keifer, O. P., Kambara, K., Lau, A., Makinson, S., & Bertrand, D. (2020) · Biochemical Pharmacology · doi:10.1016/j.bcp.2020.113889 · Cited by 28
Sanchez, M. R., Wang, Y., Cho, T. S., Schnapp, W. I., Schmit, M. B., Fang, C., & Cai, H. (2022) · Molecular Metabolism · doi:10.1016/j.molmet.2022.101443 · Cited by 28
“David Anderson’s lab at the California Institute of Technology [35] and maintained by crossing with wild-type C57BL/6 mice from the Charles River Laboratory.”
BackgroundMethodResultInfluentialSelf-citationYakhnitsa, V., Ji, G., Hein, M., Presto, P., Griffin, Z., Ponomareva, O., Navratilova, E., Porreca, F., & Neugebauer, V. (2022) · Frontiers in Pharmacology · doi:10.3389/fphar.2022.903978 · Cited by 29
Light-controlled inhibition of malignant glioma by opsin gene transfer
Yang, F., Tu, J., Pan, J.-Q., Luo, H., Liu, Y.-H., Wan, J., Zhang, J., Wei, P.-F., Jiang, T., Chen, Y.-H., et al. (2013) · Cell Death and Disease · doi:10.1038/cddis.2013.425 · Cited by 29
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
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