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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]
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“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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“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.”
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Items 201–300 of 839
Inhibitory networks of the amygdala for emotional memory
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“By contrast, neuropeptide Y (NPY) in the amygdala exerts potent anxiolytic effects (Heilig et al., 1993).”
BackgroundCell type–specific manipulation with GFP-dependent Cre recombinase
Tang, J. C. Y., Rudolph, S., Dhande, O. S., Abraira, V. E., Choi, S., Lapan, S. W., Drew, I. R., Drokhlyansky, E., Huberman, A. D., Regehr, W. G., et al. (2015) · Nature Neuroscience · doi:10.1038/nn.4081 · Cited by 81
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“…(PVN) project to the centro-lateral nucleus of the amyg- dala (CeL) (Knobloch et al., 2012), a brain region that regulates conditioned threat responses (Fanselow and Wassum, 2015; Haubensak et al., 2010; Ciocchi et al., 2010; Wilensky et al., 2006; Li et al., 2013; Ciocchi et al., 2010).”
BackgroundMultimodal mapping of cell types and projections in the central nucleus of the amygdala
Wang, Y., Krabbe, S., Eddison, M., Henry, F. E., Fleishman, G. M., Lemire, A. L., Wang, L., Korff, W. L., Tillberg, P. W., Lüthi, A., et al. (2023) · eLife · doi:10.7554/elife.84262 · Cited by 79
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“Specifically, inhibition of excitatory drive to protein kinase C-d-expressing GABAergic CeAL projection neurons would disinhibit CeAM neurons and increase fear and anxiety responses (Haubensak et al., 2010).”
Circadian regulation of membrane physiology in neural oscillators throughout the brain
Paul, J. R., Davis, J. A., Goode, L. K., Becker, B., Fusilier, A. R., Meador-Woodruff, A., & Gamble, K. L. (2019) · European Journal of Neuroscience · doi:10.1111/ejn.14343 · Cited by 81
“The lateral CeA contains “on” cells which inhibit the inhibitory “off” cells when a conditioned stimulus is present, resulting in disinhibition of the circuit that produces the fear response (Haubensak et al., 2010).”
BackgroundBu, W., Ren, H., Deng, Y., Mar, N. D., Guley, N., Moore, B. M., II, Honig, M. G., & Reiner, A. J. (2016) · Frontiers in Neuroscience · doi:10.3389/fnins.2016.00449 · Cited by 82
“Since the non-Thy1+ pyramidal neurons promote fear, their preferential preservation, together with the substantial loss of the Thy1-enriched fear-reducing pyramidal neurons may explain why TBI increases fear in our model (Haubensak et al., 2010; Herry and Johansen, 2014; Lüthi and Lüscher, 2014).”
BackgroundHernández, V. S., Hernández, O. R., de la Mora, M. P., Gómora, M. J., Fuxé, K., Eiden, L. E., & Zhang, L. (2016) · Frontiers in Neural Circuits · doi:10.3389/fncir.2016.00092 · Cited by 80
“…of detailed knowledge about GABAergic neurons in CeA involved in mediating the salience of negative (fear- and anxiety-inducing) environmental stimuli now allows more anatomically detailed inquiry into the precise role of VPMNN projections in this circuitry (for example see Haubensak et al., 2010).”
BackgroundMartinez, R. C. R., Gupta, N., Lázaro‐Muñoz, G., Sears, R. M., Kim, S., Moscarello, J. M., LeDoux, J. E., & Cain, C. K. (2013) · Learning & Memory · doi:10.1101/lm.031047.113 · Cited by 87
“Several recent papers suggest that a population of inhibitory neurons in CEL may be critical for suppressing threat reactions like freezing (Ciocchi et al. 2010; Gozzi et al. 2010; Haubensak et al. 2010).”
BackgroundCentral amygdala micro-circuits mediate fear extinction
Whittle, N., Fadok, J. P., MacPherson, K. P., Nguyen, R., Botta, P., Wolff, S. B. E., Müller, C. R., Herry, C., Tovote, P., Holmes, A., et al. (2021) · Nature Communications · doi:10.1038/s41467-021-24068-x · Cited by 87
Self-citationOptogenetics in primates: a shining future?
Gerits, A., & Vanduffel, W. (2013) · Trends in Genetics · doi:10.1016/j.tig.2013.03.004 · Cited by 82
GABAergic interneurons: The orchestra or the conductor in fear learning and memory?
Lucas, E. K., & Clem, R. L. (2017) · Brain Research Bulletin · doi:10.1016/j.brainresbull.2017.11.016 · Cited by 80
“While these effects involve interactions between spiny projection neurons rather than interneurons (Ciocchi et al., 2010; Haubensak et al., 2010), these data provide a potential model for how potentiation of inhibitory signaling among interconnected interneuron populations might also regulate the output of other brain…”
BackgroundHerman, M. A., Contet, C., & Roberto, M. (2016) · The Journal of Neuroscience · doi:10.1523/jneurosci.1267-16.2016 · Cited by 72
“For example, circuitryspecific changes in CeA processing have been implicated in conditioned fear (Haubensak et al., 2010) and in anxiety (Botta et al., 2015).”
BackgroundFunctional Circuits and Anatomical Distribution of Response Properties in the Primate Amygdala
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“Circuit-level studies, in the context of fear conditioning in rodents, have revealed that the rodent amygdala contains highly organized functional circuits that mediate the acquisition, expression, and extinction of fear memory (Paré et al., 2004; Ehrlich et al., 2009; Ciocchi et al., 2010; Haubensak et al., 2010).”
BackgroundInfluentialLocus coeruleus anchors a trisynaptic circuit controlling fear-induced suppression of feeding
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Effects of repeated stress on excitatory drive of basal amygdala neurons in vivo
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Incentive motivation: ‘wanting’ roles of central amygdala circuitry
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Calcitonin receptor signaling in the medial preoptic area enables risk-taking maternal care
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Plastic and stimulus-specific coding of salient events in the central amygdala
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“A literature search identified a BAC transgenic Prkcd-Cre mouse line termed Tg(Prkcd-glc-1/CFP,-Cre) (hereafter PrkcdCre) that was initially generated and used to drive Cre expression in the amygdala for the dissection of striatal circuitry (90).”
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“The functional ramifications of increased downstream excitability are difficult to assess, as there are multiple populations of neurons in the lateral CeA (”
Intrinsic Circuits in the Lateral Central Amygdala
Hunt, S., Sun, Y., Kucukdereli, H., Klein, R., & Sah, P. (2017) · eNeuro · doi:10.1523/eneuro.0367-16.2017 · Cited by 75
Metastable dynamics of neural circuits and networks
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Neuroanatomical phenotypes in a mouse model of the 22q11.2 microdeletion
Ellegood, J., Markx, S., Lerch, J. P., Steadman, P. E., Genç, C., Provenzano, F. A., Kushner, S. A., Henkelman, R. M., Karayiorgou, M., & Gogos, J. A. (2013) · Molecular Psychiatry · doi:10.1038/mp.2013.112 · Cited by 76
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“We recorded from the medial subdivision of the CeA (51,52), and the total neuronal population responded equally to nociceptin by decreasing GABAergic responses.”
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The central amygdala recruits mesocorticolimbic circuitry for pursuit of reward or pain
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Motivational competition and the paraventricular thalamus
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“Additionally, fi ring phenotypes in PKC δ + and Som + CeA neurons were heterogeneous [46, 48, 49] (Fig.”
BackgroundPatel, R. R., Wolfe, S. A., Bajo, M., Abeynaike, S. A., Pahng, A. R., Borgonetti, V., D’Ambrosio, S. R., Nikzad, R., Edwards, S., Paust, S., et al. (2020) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2020.101952 · Cited by 71
“The lateral CeA sends GABAergic to the medial CeA in cell type and projection-specific manner to gate behavior (Ciocchi et al. 2010; Haubensak et al. 2010; Li et al. 2013; Tye et al. 2011).”
BackgroundLesions of the posterior paraventricular nucleus of the thalamus attenuate fear expression
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“Indeed, a population of CeAL interneurons which exert inhibitory influence on the CeAL neurons that inhibit CeAM neurons has been identified (Ciocchi et al., 2010; Haubensak et al., 2010).”
BackgroundSugimura, Y. K., Takahashi, Y., Watabe, A. M., & Kato, F. (2016) · Journal of Neurophysiology · doi:10.1152/jn.00946.2015 · Cited by 69
“Its identification is an important research subject to understand the network behavior of the inhibitory circuits of the CeA (Ehrlich et al. 2009; Haubensak et al. 2010).”
BackgroundMethodInfluentialNeuronal diversity of the amygdala and the bed nucleus of the stria terminalis
Beyeler, A., & Dabrowska, J. (2020) · Handbook of behavioral neuroscience · doi:10.1016/b978-0-12-815134-1.00003-9 · Cited by 74
“Protein kinase C delta (PKCS)—Neurons expressing PKCδ are localized in the CeL and CeC (Haubensak et al., 2010).”
BackgroundResultInfluentialDynamic remodeling of a basolateral-to-central amygdala glutamatergic circuit across fear states
Hartley, N. D., Gaulden, A. D., Báldi, R., Winters, N. D., Salimando, G. J., Rosas-Vidal, L. E., Jameson, A. N., Winder, D. G., & Patel, S. (2019) · Nature Neuroscience · doi:10.1038/s41593-019-0528-7 · Cited by 72
Comparative Analysis of Neurotoxicity of Six Phthalates in Zebrafish Embryos
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“In rodents, experimental lesions and pharmacological or optogenetic manipulations of neural activity in the amygdala affect approach or defensive behaviors (Ciocchi et al., 2010; Haubensak et al., 2010; Stuber et al., 2011; Redondo et al., 2014).”
BackgroundBukalo, O., Pinard, C. R., & Holmes, A. (2014) · British Journal of Pharmacology · doi:10.1111/bph.12779 · Cited by 73
“…of the CeL’s somatostatin-positive cells contrasts with neighbouring somatostatin-negative cells, which are also GABAergic, but are defined by PKC-δ expression, and reduce CeA output and fear, consistent with the ‘CeL off’ cells discussed earlier (Haubensak et al., 2010; Amano et al., 2012).”
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“…neurons in the CeA coordinate various components of defensive or fear responses (e.g., autonomic, endocrine, behavioral) via their projections to distinct midbrain structures (e.g., hypothalamus, brainstem, and periaqueductal gray; LeDoux 2007; see also Ciocchi et al. 2010; Haubensak et al. 2010).”
BackgroundGABAergic implications in anxiety and related disorders
Arora, I., Mal, P., Arora, P., Paul, A., & Kumar, M. (2024) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2024.150218 · Cited by 74
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“BLA → CeA microcircuitry has been the focus of a number of elegant studies in the past few years (Ciocchi et al., 2010; Haubensak et al., 2010; Tye et al., 2011).”
Background2-arachidonoylglycerol signaling impairs short-term fear extinction
Hartley, N. D., Gunduz‐Cinar, O., Halladay, L. R., Bukalo, O., Holmes, A., & Patel, S. (2016) · Translational Psychiatry · doi:10.1038/tp.2016.26 · Cited by 66
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“Two of these markers, somatostatin (Sst; Cassell and Gray, 1989) and protein kinase C-d (PKC-d ; Haubensak et al., 2010), label two major populations that are largely nonoverlapping in the CeA (Haubensak et al.”
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Abstinence-dependent dissociable central amygdala microcircuits control drug craving
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Central amygdala cells for learning and expressing aversive emotional memories
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Amygdala inhibitory neurons as loci for translation in emotional memories
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Amygdala Circuits for Fear Memory: A Key Role for Dopamine Regulation
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Neural Circuit Mechanisms Underlying Emotional Regulation of Homeostatic Feeding
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A Central Amygdala-Substantia Innominata Neural Circuitry Encodes Aversive Reinforcement Signals
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“There are two major subpopulations of GABAergic neurons found in the CeL, one expressing the neuropeptide somatostatin (SOM) and the other expressing protein kinase C-delta (PKC-d) (Haubensak et al., 2010; Li et al., 2013).”
BackgroundInfluentialWood, J. C., Verma, D., Lach, G., Bonaventure, P., Herzog, H., Sperk, G., & Tasan, R. O. (2015) · Brain Structure and Function · doi:10.1007/s00429-015-1107-7 · Cited by 66
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“(+) facilitation of discrimination between cued fear vs. sustained anxiety and (−) inhibition of discrimination of cued fear vs. sustained anxiety PKCδ and CRF are indeed expressed in mutually exclusive neuronal populations in the CeA (Haubensak et al. 2010) and the BNSTdl (Daniel and Rainnie 2016).”
Oxytocin and Memory of Emotional Stimuli: Some Dance to Remember, Some Dance to Forget
Maroun, M., & Wagner, S. (2015) · Biological Psychiatry · doi:10.1016/j.biopsych.2015.07.016 · Cited by 65
Central amygdala circuit dynamics underlying the benzodiazepine anxiolytic effect
Griessner, J., Pasieka, M., Böhm, V., Groessl, F., Kaczanowska, J., Pliota, P., Kargl, D., Werner, B., Kaouane, N., Strobelt, S., et al. (2018) · Molecular Psychiatry · doi:10.1038/s41380-018-0310-3 · Cited by 64
“S9) that this could be mediated by inhibitory gating of CEAm output by the CEAl [21], potentially driven by PKCδ/SST activity [22, 32].”
BackgroundSelf-citationGüngör, N. Z., Yamamoto, R., & Paré, D. (2015) · Journal of Neurophysiology · doi:10.1152/jn.00677.2015 · Cited by 64
Synaptic potentiation in the nociceptive amygdala following fear learning in mice
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“Recent reports suggest that the CeL and/or the CeC tonically inhibit CeM, and fear learning induces disinhibition of this microcircuit [9-11].”
BackgroundResultNeuropeptide S: a novel regulator of pain-related amygdala plasticity and behaviors
Ren, W., Kiritoshi, T., Grégoire, S., Ji, G., Guerrini, R., Calò, G., & Neugebauer, V. (2013) · Journal of Neurophysiology · doi:10.1152/jn.00874.2012 · Cited by 61
“…regular-spiking type A projection neurons (Neugebauer et al. 2004; Sah et al. 2003; Schiess et al. 1999) and may correspond to PKC -negative “on” cells (Haubensak et al. 2010) that develop enhanced responses and synaptic plasticity after fear conditioning (Ciocchi et al. 2010; Watabe et al. 2013).”
BackgroundCell-Type Specificity of Neuronal Excitability and Morphology in the Central Amygdala
Adke, A. P., Khan, A., Ahn, H., Becker, J. J., Wilson, T. D., Valdivia, S., Sugimura, Y. K., González, S. M., & Carrasquillo, Y. (2020) · eNeuro · doi:10.1523/eneuro.0402-20.2020 · Cited by 59
The modulation of emotional and social behaviors by oxytocin signaling in limbic network
Triana-Del Rio, R., Ranade, S., Guardado, J., LeDoux, J., Klann, E., & Shrestha, P. (2022) · Frontiers in Molecular Neuroscience · doi:10.3389/fnmol.2022.1002846 · Cited by 58
“The centrolateral nucleus of the amygdala (CeL) is implicated in the acquisition, storage, expression, and extinction of threat-dependent memories (Ciocchi et al., 2010; Haubensak et al., 2010; Duvarci et al., 2011; Fadok et al., 2017; Terburg et al., 2018; Winter et al., 2021) and the ensuing physiological response o…”
BackgroundInfluentialNew Opportunities in Vasopressin and Oxytocin Research: A Perspective from the Amygdala
Stoop, R., Hegoburu, C., & van den Burg, E. H. (2015) · Annual Review of Neuroscience · doi:10.1146/annurev-neuro-071714-033904 · Cited by 61
“All three types can be characterized by different cytochemical markers: CeL-off neurons often express OTR, protein kinase C delta type (PKC-delta) and enkephalin (ENK; Haubensak et al. 2010).”
BackgroundWhat Can Ethobehavioral Studies Tell Us about the Brain's Fear System?
Pellman, B. A., & Kim, J. J. (2016) · Trends in Neurosciences · doi:10.1016/j.tins.2016.04.001 · Cited by 67
“For example, functional and genetic circuit analyses have shown that the lateral subdivision of the CEA (CEl) is involved in the acquisition of auditory fear conditioning, whereas the medial subdivision of the CEA (CEm) mediates the expression of fear CRs [38,39].”
BackgroundWeir, G. A., Middleton, S. J., Clark, A. J., Daniel, T., Khovanov, N., McMahon, S. B., & Bennett, D. (2017) · Brain · doi:10.1093/brain/awx201 · Cited by 61
“…need to gener- ate two independent AAVs expressing each subunit is a disadvantage when trying to silence a broad range of sen- sory neurons; however, certain paradigms can exploit this by using two independent promoters to express the sub- units in an intersectional manner (Haubensak et al., 2010).”
BackgroundStress peptides sensitize fear circuitry to promote passive coping
Pliota, P., Böhm, V., Groessl, F., Griessner, J., Valenti, O., Kraitsy, K., Kaczanowska, J., Pasieka, M., Lendl, T., Deussing, J. M., et al. (2018) · Molecular Psychiatry · doi:10.1038/s41380-018-0089-2 · Cited by 59
“Recent seemingly contradictory findings on the specific role and mechanism of CEl PKCδ+ [11, 15] or CEl SOM+ [9, 13] cells in modulating Pavlovian fear indicate that future studies on CE neuronal function and dynamics are clearly needed.”
InfluentialSelf-citationEmbracing Complexity in Defensive Networks
Headley, D. B., Kanta, V., Kyriazi, P., & Paré, D. (2019) · Neuron · doi:10.1016/j.neuron.2019.05.024 · Cited by 61
“Previously, it had been reported that these PKC-δ+ cells inhibit conditioned freezing (Ciocchi et al., 2010; Haubensak et al., 2010), leading to the expectation that optogenetically exciting PKC-δ+ neurons would decrease freezing and result in more exploration of the open areas in the EPM and OF.”
BackgroundRajbhandari, A. K., Octeau, C. J., Gonzalez, S. T., Pennington, Z. T., Mohamed, F., Trott, J. M., Chavez, J., Ngyuen, E., Keces, N., Hong, W., et al. (2021) · Journal of Neuroscience · doi:10.1523/jneurosci.2564-20.2021 · Cited by 59
“Indirect microcircuits include relays in the lateral portion of the CN (Haubensak et al., 2010; Li et al., 2013) as well as clusters of GABAergic cells that lie in the capsule separating BLA and CN (Pare et al.”
BackgroundSelf-citationLiu, Y., Ehrengruber, M. U., Negwer, M., Shao, H., Cetin, A. H., & Lyon, D. C. (2013) · Current Biology · doi:10.1016/j.cub.2013.07.033 · Cited by 52
“The most successful approaches thus far have used transgenic mouse lines to target and enhance the necessary gene expression [17–20].”
Ominous odors: olfactory control of instinctive fear and aggression in mice
Stowers, L., Cameron, P. A., & Keller, J. A. (2013) · Current Opinion in Neurobiology · doi:10.1016/j.conb.2013.01.007 · Cited by 59
“While recent work has revealed many of the details of associative fear circuits [4,30–33], the identification of the neurons in the central nervous system that are necessary and sufficient for instinctive fear and aggression, how they are genetically specified, and how they fit into the overall control of behavior in…”
BackgroundCatching the engram: strategies to examine the memory trace
Sakaguchi, M., & Hayashi, Y. (2012) · Molecular Brain · doi:10.1186/1756-6606-5-32 · Cited by 58
“Such light activated proteins make it possible to precisely control the temporal and spatial activity of neurons in vivo [25,65,67-71].”
BackgroundCorticotropin-Releasing Factor (CRF) and Addictive Behaviors
Roberto, M., Spierling, S. R., Kirson, D., & Zorrilla, E. P. (2017) · International review of neurobiology · doi:10.1016/bs.irn.2017.06.004 · Cited by 62
“For example, circuitry-specific changes in CeA processing have been implicated in conditioned fear (Haubensak et al., 2010) and in anxiety (Botta et al., 2015).”
BackgroundShallcross, J., Hámor, P. U., Bechard, A. R., Romano, M., Knackstedt, L. A., & Schwendt, M. (2019) · Frontiers in Behavioral Neuroscience · doi:10.3389/fnbeh.2019.00091 · Cited by 61
“, 1992), and serves to regulate fear response through output to the central amygdala (CeA) and brainstem regions (Royer et al., 1999; Haubensak et al., 2010).”
BackgroundRemembering Another Aspect of Forgetting
Jasnow, A. M., Cullen, P. K., & Riccio, D. C. (2012) · Frontiers in Psychology · doi:10.3389/fpsyg.2012.00175 · Cited by 61
“…fear, whereas the hippocampus is generally thought to be essential in the regulation of contextual fear (Kim et al., 1993; Fanselow and Kim, 1994; Helmstetter and Bellgowan, 1994; Maren, 1999; Davis and Aggleton, 2000; Schafe et al., 2001; Walker et al., 2002; Phelps et al., 2004; Myers, 2006).”
BackgroundRevealing the secrets of neuronal circuits with recombinant rabies virus technology
Ginger, M. R., Haberl, M. G., Conzelmann, K., Schwarz, M. K., & Frick, A. (2013) · Frontiers in Neural Circuits · doi:10.3389/fncir.2013.00002 · Cited by 59
“…of morphological markers permits the dynamic observation of processes such as spine stability/turnover in living animals (for a recent review see Holtmaat and Svoboda, 2009), and likely satisfies the requirements for super-resolution imaging at nanoscale resolution (for review, see references…”
BackgroundChiang, P., Chien, T.-C., Chen, C., Yanagawa, Y., & Lien, C. (2015) · Scientific Reports · doi:10.1038/srep10143 · Cited by 60
Palomares-Castillo, E., Hernández‐Pérez, O. R., Pérez-Carrera, D., Crespo‐Ramírez, M., Fuxé, K., & de la Mora, M. P. (2012) · Brain Research · doi:10.1016/j.brainres.2012.03.047 · Cited by 56
“Consistent with these results CELoff neurons were found to fully overlap with a population of CeL neurons that express PKC-δ and most importantly with an enhancement of freezing behavior after its genetic silencing (Haubensak et al., 2010).”
Herman, M. A., Kallupi, M., Luu, G., Oleata, C. S., Heilig, M. A., Koob, G. F., Ciccocioppo, R., & Roberto, M. (2012) · Neuropharmacology · doi:10.1016/j.neuropharm.2012.11.026 · Cited by 55
“(Cruz et al., 2012; Haubensak et al., 2010; Roberto et al., 2004).”
MethodTime Determines the Neural Circuit Underlying Associative Fear Learning
Guimarãis, M., Gregório, A. C., Cruz, A., Guyon, N., & Moita, M. A. P. (2011) · Frontiers in Behavioral Neuroscience · doi:10.3389/fnbeh.2011.00089 · Cited by 60
“BEHAVIORAL NEUROSCIENCE ORIGINAL RESEARCH ARTICLE published: 27 December 2011 doi: 10.3389/fnbeh.2011.00089 Time determines the neural circuit underlying associative fear learning”
BackgroundInfluentialLong-Term Neural Correlates of Reversible Fear Learning in the Lateral Amygdala
An, B., Hong, I., & Choi, S. (2012) · Journal of Neuroscience · doi:10.1523/jneurosci.3017-12.2012 · Cited by 57
“Alternatively, reversible LA neuronal firing may alter activity of the amygdala-intercalated neurons and inhibitory CeL neurons that tonically inhibit the major projection neurons in the CeM (Paré et al., 2004; Amano et al., 2010; Haubensak et al., 2010).”
BackgroundInfluentialThe center of the emotional universe: Alcohol, stress, and CRF1 amygdala circuitry
Agoglia, A. E., & Herman, M. A. (2018) · Alcohol · doi:10.1016/j.alcohol.2018.03.009 · Cited by 57
Neugebauer, V. (2020) · Handbook of behavioral neuroscience · doi:10.1016/b978-0-12-815134-1.00004-0 · Cited by 58
“The original assumption was that nonaccommodating or regular spiking neurons represent peptidergic projection neurons (Schiess, Callahan, & Zheng, 1999), which would largely correspond to PKCdelta negative neurons (Haubensak et al., 2010) (see “Cell types“ in “Amygdala neurocircuitry of ‘pain processing’“).”
BackgroundThe ventromedial hypothalamus mediates predator fear memory
Silva, B. A., Mattucci, C., Krzywkowski, P., Cuozzo, R., Carbonari, L., & Gross, C. T. (2016) · European Journal of Neuroscience · doi:10.1111/ejn.13239 · Cited by 53
“have been shown to encode and support the cue-dependent acquisition and recall of fear memory (Walker & Davis, 2002; Ehrlich et al., 2009; Gozzi et al., 2010; Haubensak et al., 2010; Wolff et al., 2014).”
BackgroundLi, J.-N., & Sheets, P. L. (2019) · Pain · doi:10.1097/j.pain.0000000000001691 · Cited by 52
“Pivotal work shows that PKC-d1 neurons inhibit CeM output to the periaqueductal gray (PAG).(34,47) The PAG is a midbrain structure that integrates”
BackgroundInfluentialCastellano, D., Shepard, R. D., & Lü, W. (2021) · Frontiers in Neuroscience · doi:10.3389/fnins.2020.616298 · Cited by 54
Design of a Neurally Plausible Model of Fear Learning
Krasne, F. B., Fanselow, M. S., & Zelikowsky, M. (2011) · Frontiers in Behavioral Neuroscience · doi:10.3389/fnbeh.2011.00041 · Cited by 51
Self-citationMazzitelli, M., Yakhnitsa, V., Neugebauer, B., & Neugebauer, V. (2022) · Neuropharmacology · doi:10.1016/j.neuropharm.2022.109031 · Cited by 52
Jo, Y. S., Namboodiri, V. M. K., Stuber, G. D., & Zweifel, L. S. (2020) · Nature Communications · doi:10.1038/s41467-020-14393-y · Cited by 53
Protein Kinase Cδ Mediates Histamine-Evoked Itch and Responses in Pruriceptors
Valtcheva, M. V., Davidson, S., Zhao, C., Leitges, M., & Gereau, R. W. (2015) · Molecular Pain · doi:10.1186/1744-8069-11-1 · Cited by 51
“PKCδ is expressed in a variety of tissues, including the brain and peripheral nervous system [19,21,23-30].”
BackgroundTranscriptome Alterations in Posttraumatic Stress Disorder
Girgenti, M. J., & Duman, R. S. (2017) · Biological Psychiatry · doi:10.1016/j.biopsych.2017.09.023 · Cited by 52
Yuan, F., Jiang, H., Yin, H., Jiang, X., Jiao, F., Chen, S., Ying, H., Chen, Y., Zhai, Q., & Guo, F. (2020) · Nature Communications · doi:10.1038/s41467-020-16662-2 · Cited by 51
Cells and circuits for amygdala neuroplasticity in the transition to chronic pain
Kiritoshi, T., Yakhnitsa, V., Singh, S., Wilson, T. D., Chaudhry, S., Neugebauer, B., Torres-Rodriguez, J. M., Lin, J. J., Carrasquillo, Y., & Neugebauer, V. (2024) · Cell Reports · doi:10.1016/j.celrep.2024.114669 · Cited by 58
Ting, J. T., & Feng, G. (2013) · Behavioural Brain Research · doi:10.1016/j.bbr.2013.02.037 · Cited by 50
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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