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Raphe GABAergic Neurons Mediate the Acquisition of Avoidance after Social Defeat
Open accessAbstract
Serotonin (5-HT) modulates neural responses to socioaffective cues and can bias approach or avoidance behavioral decisions, yet the cellular mechanisms underlying its contribution to the regulation of social experiences remain poorly understood. We hypothesized that GABAergic neurons in the dorsal raphe nucleus (DRN) may participate in socioaffective regulation by controlling serotonergic tone during social interaction. We tested this hypothesis using whole-cell recording techniques in genetically identified DRN GABA and 5-HT neurons in mice exposed to social defeat, a model that induces long-lasting avoidance behaviors in a subset of mice responsive to serotonergic antidepressants. Our results revealed that social defeat engaged DRN GABA neurons and drove GABAergic sensitization that strengthened inhibition of 5-HT neurons in mice that were susceptible, but not resilient to social defeat. Furthermore, optogenetic silencing of DRN GABA neurons disinhibited neighboring 5-HT neurons and prevented the acquisition of social avoidance in mice exposed to a social threat, but did not affect a previously acquired avoidance phenotype. We provide the first characterization of GABA neurons in the DRN that monosynaptically inhibit 5-HT neurons and reveal their key role in neuroplastic processes underlying the development of social avoidance.
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“Yet, this increased reliance on the spectator relative to the actor model following uncontrollable stressors probably involves several other brain areas, including the mPFC and the dorsal raphe nucleus, both of which are highly sensitive to stressor controllability [14][15][16] .”
From Stress-sensitive inference of task controllability (2022) · cites this paper as [16]
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Cites
An Integrative Theory of Prefrontal Cortex Function
Miller, E. K., & Cohen, J. D. (2001) · Annual Review of Neuroscience · doi:10.1146/annurev.neuro.24.1.167 · Cited by 12,803
A robust and high-throughput Cre reporting and characterization system for the whole mouse brain
Madisen, L., Zwingman, T. A., Sunkin, S. M., Oh, S. W., Zariwala, H. A., Gu, H., Ng, L. L., Palmiter, R. D., Hawrylycz, M. J., Jones, A. R., et al. (2010) · Nature Neuroscience · doi:10.1038/nn.2467 · Cited by 6,907
Krishnan, V., Han, M.-H., Graham, D. L., Berton, O., Renthal, W., Russo, S. J., LaPlant, Q., Graham, A., Lutter, M., Lagace, D. C., et al. (2007) · Cell · doi:10.1016/j.cell.2007.09.018 · Cited by 2,307
Self-citationEssential role of BDNF in the mesolimbic dopamine pathway in social defeat stress
Berton, O., McClung, C. A., DiLeone, R. J., Krishnan, V., Renthal, W., Russo, S. J., Graham, D., Tsankova, N. M., Bolanos, C. A., Rios, M., et al. (2006) · Science · doi:10.1126/science.1120972 · Cited by 2,129
Self-citationA resource of Cre driver lines for genetic targeting of GABAergic neurons in cerebral cortex
Taniguchi, H., He, M., Wu, P., Kim, S., Paik, R., Sugino, K., Kvitsani, D., Fu, Y., Lu, J., Lin, Y., et al. (2011) · Neuron · doi:10.1016/j.neuron.2011.07.026 · Cited by 1,828
Sustained hippocampal chromatin regulation in a mouse model of depression and antidepressant action
Tsankova, N. M., Berton, O., Renthal, W., Kumar, A., Neve, R. L., & Nestler, E. J. (2006) · Nature Neuroscience · doi:10.1038/nn1659 · Cited by 1,780
Self-citationA standardized protocol for repeated social defeat stress in mice
Golden, S. A., Covington, H. E., Berton, O., & Russo, S. J. (2011) · Nature Protocols · doi:10.1038/nprot.2011.361 · Cited by 1,581
Self-citationThe Evolution of the Cognitive Model of Depression and Its Neurobiological Correlates
Beck, A. T. (2008) · American Journal of Psychiatry · doi:10.1176/appi.ajp.2008.08050721 · Cited by 1,537
High-performance genetically targetable optical neural silencing by light-driven proton pumps
Chow, B. Y., Han, X., Dobry, A. S., Qian, X., Chuong, A. S., Li, M., Henninger, M. A., Belfort, G. M., Lin, Y., Monahan, P. E., et al. (2010) · Nature · doi:10.1038/nature08652 · Cited by 1,188
Long story short: the serotonin transporter in emotion regulation and social cognition
Canli, T., & Lesch, K.-P. (2007) · Nature Neuroscience · doi:10.1038/nn1964 · Cited by 1,034
Amat, J., Baratta, M. V., Paul, E., Bland, S. T., Watkins, L. R., & Maier, S. F. (2005) · Nature Neuroscience · doi:10.1038/nn1399 · Cited by 931
Social Bonds and Posttraumatic Stress Disorder
Charuvastra, A., & Cloitre, M. (2008) · Annual Review of Psychology · doi:10.1146/annurev.psych.58.110405.085650 · Cited by 911
Ventromedial prefrontal–subcortical systems and the generation of affective meaning
Roy, M., Shohamy, D., & Wager, T. D. (2012) · Trends in Cognitive Sciences · doi:10.1016/j.tics.2012.01.005 · Cited by 856
Allen Brain Atlas: an integrated spatio-temporal portal for exploring the central nervous system
Sunkin, S. M., Ng, L., Lau, C., Dolbeare, T., Gilbert, T. L., Thompson, C. L., Hawrylycz, M., & Dang, C. (2012) · Nucleic Acids Research · doi:10.1093/nar/gks1042 · Cited by 796 · cited 1×
“Viral tracing studies from the Allen Brain Atlas (Sunkin et al., 2013), corroborated by our own anterograde tracing data (Fig.”
Mattis, J., Tye, K. M., Ferenczi, E. A., Ramakrishnan, C., O'Shea, D. J., Prakash, R., Gunaydin, L. A., Hyun, M., Fenno, L. E., Gradinaru, V., et al. (2012) · Nature Methods · doi:10.1038/nmeth.1808 · Cited by 780
A prefrontal cortex–brainstem neuronal projection that controls response to behavioural challenge
Warden, M. R., Selimbeyoglu, A., Mirzabekov, J. J., Lo, M., Thompson, K. R., Kim, S.-Y., Adhikari, A., Tye, K. M., Frank, L. M., & Deisseroth, K. (2012) · Nature · doi:10.1038/nature11617 · Cited by 645
Chattopadhyaya, B., Di Cristo, G., Higashiyama, H., Knott, G. W., Kuhlman, S. J., Welker, E., & Huang, Z. J. (2004) · The Journal of Neuroscience · doi:10.1523/jneurosci.1851-04.2004 · Cited by 596
Cognitive Mechanisms of Treatment in Depression
Roiser, J. P., Elliott, R., & Sahakian, B. J. (2012) · Neuropsychopharmacology · doi:10.1038/npp.2011.183 · Cited by 535
Interpersonal Processes in Depression
Hames, J. L., Hagan, C. R., & Joiner, T. E. (2013) · Annual Review of Clinical Psychology · doi:10.1146/annurev-clinpsy-050212-185553 · Cited by 499
Celada, P., Puig, M. V., Casanovas, J. M., Guillazo, G., & Artigas, F. (2001) · The Journal of Neuroscience · doi:10.1523/jneurosci.21-24-09917.2001 · Cited by 497
Serotonergic mechanisms promote dominance acquisition in adult male vervet monkeys
Raleigh, M. J., McGuire, M. T., Brammer, G. L., Pollack, D. B., & Yuwiler, A. (1991) · Brain Research · doi:10.1016/0006-8993(91)90001-c · Cited by 450
Social model of depression in mice of C57BL/6J strain
Kudryavtseva, N. N., Bakshtanovskaya, I. V., & Koryakina, L. A. (1991) · Pharmacology Biochemistry and Behavior · doi:10.1016/0091-3057(91)90284-9 · Cited by 404
Todorov, A. (2008) · Annals of the New York Academy of Sciences · doi:10.1196/annals.1440.012 · Cited by 382
Black sheep get the blues: a psychobiological model of social rejection and depression
Slavich, G. M., O’Donovan, A., Epel, E. S., & Kemeny, M. E. (2010) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2010.01.003 · Cited by 362
Neural mechanisms of social risk for psychiatric disorders
Meyer‐Lindenberg, A., & Tost, H. (2012) · Nature Neuroscience · doi:10.1038/nn.3083 · Cited by 354
Antidepressant-Like Effects of Medial Prefrontal Cortex Deep Brain Stimulation in Rats
Hamani, C., Diwan, M., Macedo, C. E., Brandão, M. L., Shumake, J., Gonzalez-Lima, F., Raymond, R., Lozano, A. M., Fletcher, P. J., & Nobrega, J. N. (2010) · Biological Psychiatry · doi:10.1016/j.biopsych.2009.08.025 · Cited by 324 · cited 1×
“Our results are consistent with the antidepressant-like effects of vmPFC DBS in rats, which increases 5-HT output in certain forebrain projection areas (Hamani et al., 2010; Hamani et al., 2012).”
ResultChiba, T., Kayahara, T., & Nakano, K. (2001) · Brain Research · doi:10.1016/s0006-8993(00)03013-4 · Cited by 290
Systematic review of the neural basis of social cognition in patients with mood disorders
Cusi, A. M., Nazarov, A., Holshausen, K., MacQueen, G. M., & McKinnon, M. C. (2012) · Journal of Psychiatry and Neuroscience · doi:10.1503/jpn.100179 · Cited by 278
Bruchas, M. R., Schindler, A. G., Shankar, H., Messinger, D. I., Miyatake, M., Land, B. B., Lemos, J. C., Hagan, C. E., Neumaier, J. F., Quintana, A., et al. (2011) · Neuron · doi:10.1016/j.neuron.2011.06.011 · Cited by 273
Rogers, R. D. (2010) · Neuropsychopharmacology · doi:10.1038/npp.2010.165 · Cited by 262
Calizo, L. H., Akanwa, A., Ma, X., Pan, Y.-Z., Lemos, J. C., Craige, C., Heemstra, L. A., & Beck, S. G. (2011) · Neuropharmacology · doi:10.1016/j.neuropharm.2011.04.008 · Cited by 252
Self-citationAlekseyenko, O. V., Lee, C. M., & Kravitz, E. A. (2010) · PLoS ONE · doi:10.1371/journal.pone.0010806 · Cited by 237
A genetic approach to access serotonin neurons for in vivo and in vitro studies
Scott, M. M., Wylie, C. J., Lerch, J. K., Murphy, R., Lobur, K. J., Herlitze, S., Jiang, W., Conlon, R. A., Strowbridge, B. W., & Deneris, E. S. (2005) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0504510102 · Cited by 233
(2005) · PubMed · Cited by 221
Circuitry Underlying Regulation of the Serotonergic System by Swim Stress
Roche, M., Commons, K. G., Peoples, A., & Valentino, R. J. (2003) · Journal of Neuroscience · doi:10.1523/jneurosci.23-03-00970.2003 · Cited by 207
Liu, R., Jolas, T., & Aghajanian, G. K. (2000) · Brain Research · doi:10.1016/s0006-8993(00)02468-9 · Cited by 197
Jankowski, M. P., & Sesack, S. R. (2004) · Journal of Comparative Neurology · doi:10.1002/cne.10976 · Cited by 186
Chemical neuroanatomy of the dorsal raphe nucleus and adjacent structures of the mouse brain
Fu, W.-Y., Maître, E. L., Fabre, V., Bernard, J., Xu, Q., & Hökfelt, T. G. M. (2010) · The Journal of Comparative Neurology · doi:10.1002/cne.22407 · Cited by 186
Pet-1 is required across different stages of life to regulate serotonergic function
Liu, C., Maejima, T., Wyler, S. C., Casadesús, G., Herlitze, S., & Deneris, E. S. (2010) · Nature Neuroscience · doi:10.1038/nn.2623 · Cited by 183
Projections and interconnections of genetically defined serotonin neurons in mice
Bang, S. J., Jensen, P., Dymecki, S. M., & Commons, K. G. (2012) · European Journal of Neuroscience · doi:10.1111/j.1460-9568.2011.07936.x · Cited by 181
Hamani, C., Machado, D. C., Hipólide, D. C., Dubiela, F. P., Suchecki, D., de Macedo, C. E. A., Tescarollo, F. C., Martins, U., Covolan, L., & Nóbrega, J. N. (2011) · Biological Psychiatry · doi:10.1016/j.biopsych.2011.08.025 · Cited by 178
Anterior Prefrontal Cortex Inhibition Impairs Control over Social Emotional Actions
Volman, I., Roelofs, K., Koch, S. B. J., Verhagen, L., & Toni, I. (2011) · Current Biology · doi:10.1016/j.cub.2011.08.050 · Cited by 160
Espallergues, J., Teegarden, S. L., Veerakumar, A., Boulden, J., Challis, C., Jochems, J., Chan, M., Petersen, T. L., Deneris, E. S., Matthias, P., et al. (2012) · Journal of Neuroscience · doi:10.1523/jneurosci.5634-11.2012 · Cited by 151
Self-citationVarga, V., Székely, A. D., Csillag, A., Sharp, T., & Hajós, M. (2001) · Neuroscience · doi:10.1016/s0306-4522(01)00294-9 · Cited by 147
Passamonti, L., Crockett, M. J., Apergis-Schoute, A. M., Clark, L., Rowe, J. B., Calder, A. J., & Robbins, T. W. (2011) · Biological Psychiatry · doi:10.1016/j.biopsych.2011.07.033 · Cited by 143
Varga, V., Kocsis, B., & Sharp, T. (2003) · European Journal of Neuroscience · doi:10.1046/j.1460-9568.2003.02465.x · Cited by 134
Induction of ΔFosB in the Periaqueductal Gray by Stress Promotes Active Coping Responses
Berton, O., Covington, H. E., Ebner, K., Tsankova, N. M., Carle, T. L., Ulery, P., Bhonsle, A., Barrot, M., Krishnan, V., Singewald, G. M., et al. (2007) · Neuron · doi:10.1016/j.neuron.2007.06.033 · Cited by 129
Self-citationVaucher, E., Tong, X., Cholet, N., Lantin, S., & Hamel, É. (2000) · The Journal of Comparative Neurology · doi:10.1002/(sici)1096-9861(20000529)421:2 · Cited by 126
Phan, K. L., Coccaro, E. F., Angstadt, M., Kreger, K. J., Mayberg, H. S., Liberzon, I., & Stein, M. B. (2013) · Biological Psychiatry · doi:10.1016/j.biopsych.2012.10.003 · Cited by 114 · cited 2×
“…to psychosocial threats such as social rejection, a common precipitant of the onset or relapse of affective disorders in vulnerable individuals (Charuvastra and Cloitre, 2008; Slavich et al., 2010; Cusi et al., 2012; Meyer-Lindenberg and Tost, 2012; Phan et al., 2013; Hames et al., 2013).”
BackgroundTakahashi, A., Shimamoto, A., Boyson, C. O., DeBold, J. F., & Miczek, K. A. (2010) · Journal of Neuroscience · doi:10.1523/jneurosci.1814-10.2010 · Cited by 111
Cortical Control of Affective Networks
Kumar, S., Black, S. J., Hultman, R., Szabo, S. T., DeMaio, K. D., Du, J., Katz, B. M., Feng, G., Covington, H. E., & Dzirasa, K. (2013) · The Journal of Neuroscience · doi:10.1523/jneurosci.0092-12.2013 · Cited by 110
The effect of raising and lowering tryptophan levels on human mood and social behaviour
Young, S. N. (2013) · Philosophical Transactions of the Royal Society B Biological Sciences · doi:10.1098/rstb.2011.0375 · Cited by 105
Konishi, H., & Nakajima, T. (1978) · PubMed · Cited by 102
Crawford, L. K., Craige, C. P., & Beck, S. G. (2010) · Journal of Neurophysiology · doi:10.1152/jn.01132.2009 · Cited by 96
Self-citationBrown, R. E., McKenna, J. T., Winston, S. H., Basheer, R., Yanagawa, Y., Thakkar, M. M., & McCarley, R. W. (2008) · European Journal of Neuroscience · doi:10.1111/j.1460-9568.2008.06024.x · Cited by 92
Paul, E. D., Hale, M. W., Lukkes, J. L., Valentine, M. J., Sarchet, D. M., & Lowry, C. A. (2011) · Physiology & Behavior · doi:10.1016/j.physbeh.2011.01.006 · Cited by 90
McKenna, J. T., Yang, C. Z., Franciosi, S., Winston, S. H., Abarr, K. K., Rigby, M., Yanagawa, Y., McCarley, R. W., & Brown, R. E. (2012) · The Journal of Comparative Neurology · doi:10.1002/cne.23290 · Cited by 81
A single social defeat reduces aggression in a highly aggressive strain of Drosophila
Penn, J. K. M., Zito, M. F., & Kravitz, E. A. (2010) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1007016107 · Cited by 64
Bang, S. J., & Commons, K. G. (2012) · The Journal of Comparative Neurology · doi:10.1002/cne.23146 · Cited by 58
Wierenga, C. J., Müllner, F. E., Rinke, I., Keck, T., Stein, V., & Bonhoeffer, T. (2010) · PLoS ONE · doi:10.1371/journal.pone.0015915 · Cited by 52
Social Stress Alters Inhibitory Synaptic Input to Distinct Subpopulations of Raphe Serotonin Neurons
Crawford, L. K., Rahman, S. F., & Beck, S. G. (2013) · ACS Chemical Neuroscience · doi:10.1021/cn300238j · Cited by 45
Self-citationThe Use of Animal Models in Psychiatric Research and Treatment
Krishnan, V., Berton, O., & Nestler, E. J. (2008) · American Journal of Psychiatry · doi:10.1176/appi.ajp.2008.08071076 · Cited by 44
Self-citationSubmissive behavior in mice as a test for antidepressant drug activity
Malatyńska, E., Rapp, R., Harrawood, D., & Tunnicliff, G. (2005) · Pharmacology Biochemistry and Behavior · doi:10.1016/j.pbb.2005.08.020 · Cited by 43
Takahashi, A., Nitenson, A. S., Kim, J.-S., DeBold, J. F., Koide, T., & Miczek, K. A. (2012) · Psychopharmacology · doi:10.1007/s00213-012-2654-8 · Cited by 35
Bilderbeck, A. C., McCabe, C., Wakeley, J., McGlone, F., Harris, T., Cowen, P. J., & Rogers, R. D. (2011) · Biological Psychiatry · doi:10.1016/j.biopsych.2010.12.038 · Cited by 34
Ettenberg, A., Ofer, O. A., Mueller, C. L., Waldroup, S. A., Cohen, A., & Ben‐Shahar, O. (2010) · Pharmacology Biochemistry and Behavior · doi:10.1016/j.pbb.2010.11.008 · Cited by 27
Crawford, L. K., Craige, C. P., & Beck, S. G. (2011) · European Journal of Neuroscience · doi:10.1111/j.1460-9568.2011.07882.x · Cited by 21
Self-citationHou, C., Li, X., Feng, J., Zhang, L., Wang, Y., Chen, L., Wang, T., Zhang, Q. J., & Liu, J.-R. (2012) · Neurochemistry International · doi:10.1016/j.neuint.2012.09.012 · Cited by 17
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Metadata
- Authors
- Challis, C., Boulden, J., Veerakumar, A., Espallergues, J., Vassoler, F. M., Pierce, R. C., Beck, S. G., & Berton, O.
- Affiliations
- University of Pennsylvania (US)
- Children's Hospital of Philadelphia (US)
- Venue
- Journal of Neuroscience
- Publisher
- Society for Neuroscience
- Published
- 2013-08-28
- Volume
- 33
- Issue
- 35
- Pages
- 13978-13988
- ISSN
- 0270-6474 (ISSN-L)
- 1529-2401
- PMC
- PMC3756748
- OpenAlex
- W2010788510
- Cited by
- 197
- References
- 68
- Citations by year
- 2026: 7 · 2025: 8 · 2024: 16 · 2023: 10 · 2022: 14 · 2021: 14 · 2020: 18 · 2019: 15 · 2018: 17 · 2017: 21 · 2016: 10 · 2015: 20 · 2014: 25 · 2013: 2
- FWCI
- 9.33
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Neuroscience (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- International Mental Health Research Organization
- National Institutes of Health (DA22339, DA18678)
- National Institute of Mental Health (R01MH087581, MH0754047, F31MH097386, RC1MH089800, T32MH014654, MH087581, MH089800)
- National Institute on Drug Abuse (DA22339, DA18678, R01DA022339, K02DA018678)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Health Sciences › Medicine › Pharmacology (medical) › Treatment of Major Depression
- Keywords
- dorsal raphe nucleus, GABAergic neurons, serotonergic neurons, social defeat, social avoidance, social resilience, optogenetic silencing, neuroplasticity, social interaction
- MeSH terms
- Aggression, Animals, Avoidance Learning, Male, Mice, Inbred C57BL, Phenotype, Raphe Nuclei, Excitatory Postsynaptic Potentials, Mice, Inhibitory Postsynaptic Potentials, Serotonergic Neurons, GABAergic Neurons, Optogenetics
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