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Stress is considered to be one of the common pathogenic factors leading to mental disorders. Acute severe stress events or chronic distress could lead to depression and psychiatric disorders. Therefore, the establishment of stress animal models in the laboratory to mimic the stress suffering in humans would be beneficial for better understanding the etiology and mechanisms underlying stress-induced mental disorders. In addition, the development of powerful tools such as optogenetics and chemogenetics has made more rapid progress to reveal the critical neural circuits in regulating the pathogenesis of stress-induced disorders. This review firstly summarized the well-established different types of stress animal models widely used in the laboratory including acute stress models, chronic stress models, models of surgical stress, drug-induced stress models, and genetic mutation-associated stress models. Moreover, we also summarized the latest progress in understanding the characteristics and mechanisms of stress-related neurocircuits that are critical for discovering novel therapeutic strategies for stress-induced mental disorders.


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Animal models of stress and stress-related neurocircuits: A comprehensive review

Show Author's information Mengxin Ma1,2,§Xin Chang1,§Haitao Wu1,3,4( )
Department of Neurobiology, Beijing Institute of Basic Medical Sciences, Beijing 100850, China
Beijing Institute for Brain Disorders, Capital Medical University, Beijing 100069, China
Chinese Institute for Brain Research, Beijing 102206, China
Key Laboratory of Neuroregeneration, Co-innovation Center of Neuroregeneration, Nantong University, Nantong, 226019, China

§ Mengxin Ma and Xin Chang contributed equally to this work.

Abstract

Stress is considered to be one of the common pathogenic factors leading to mental disorders. Acute severe stress events or chronic distress could lead to depression and psychiatric disorders. Therefore, the establishment of stress animal models in the laboratory to mimic the stress suffering in humans would be beneficial for better understanding the etiology and mechanisms underlying stress-induced mental disorders. In addition, the development of powerful tools such as optogenetics and chemogenetics has made more rapid progress to reveal the critical neural circuits in regulating the pathogenesis of stress-induced disorders. This review firstly summarized the well-established different types of stress animal models widely used in the laboratory including acute stress models, chronic stress models, models of surgical stress, drug-induced stress models, and genetic mutation-associated stress models. Moreover, we also summarized the latest progress in understanding the characteristics and mechanisms of stress-related neurocircuits that are critical for discovering novel therapeutic strategies for stress-induced mental disorders.

Keywords:

stress models, mental disorders, neurocircuits, optogenetics
Received: 12 February 2021 Revised: 21 April 2021 Accepted: 07 May 2021 Published: 25 June 2021 Issue date: December 2021
References(131)
[1]
Lisman, J., Buzsáki, G., Eichenbaum, H., Nadel, L., Ranganath, C., Redish, A. D. Viewpoints: how the hippocampus contributes to memory, navigation and cognition. Nature Neuroscience, 2017, 20(11): 1434-1447.
[2]
Hammen, C. Stress and depression. Annual Review of Clinical Psychology, 2005, 1: 293-319.
[3]
Greenberg, N., Carr, J. A., Summers, C. H. Causes and consequences of stress. Integrative and Comparative Biology, 2002, 42(3): 508-516.
[4]
Fox, M. E., Lobo, M. K. The molecular and cellular mechanisms of depression: A focus on reward circuitry. Molecular Psychiatry, 2019, 24(12): 1798-1815.
[5]
Henn, F. A., Vollmayr, B. Stress models of depression: Forming genetically vulnerable strains. Neuroscience & Biobehavioral Reviews, 2005, 29(4-5): 799-804.
[6]
Malhi, G. S., Mann, J. J. Depression. The Lancet, 2018, 392(10161): 2299-2312.
[7]
Kumar, V., Bhat, Z. A., Kumar, D. Animal models of anxiety: A comprehensive review. Journal of Pharmacological and Toxicological Methods, 2013, 68(2): 175-183.
[8]
Grosenick, L., Shi, T. C., Gunning, F. M., Dubin, M. J., Downar, J., Liston, C. Functional and optogenetic approaches to discovering stable subtype-specific circuit mechanisms in depression. Biological Psychiatry Cognitive Neuroscience and Neuroimaging, 2019, 4(6): 554-566.
[9]
Nestler, E. J., Hyman, S. E. Animal models of neuropsychiatric disorders. Nature Neuroscience, 2010, 13(10): 1161-1169.
[10]
Belzung, C., Griebel, G. Measuring normal and pathological anxiety-like behaviour in mice: A review. Behavioural Brain Research, 2001, 125(1-2): 141-149.
[11]
Hao, Y. Z., Ge, H. X., Sun, M. Y., Gao, Y. Selecting an appropriate animal model of depression. International Journal of Molecular Sciences, 2019, 20(19): 4827.
[12]
Glavin, G. B., Paré, W. P., Sandbak, T., Bakke, H. K., Murison, R. Restraint stress in biomedical research: An update. Neuroscience & Biobehavioral Reviews, 1994, 18(2): 223-249.
[13]
Buynitsky, T., Mostofsky, D. I. Restraint stress in biobehavioral research: Recent developments. Neuroscience & Biobehavioral Reviews, 2009, 33(7): 1089-1098.
[14]
McLaughlin, K. J., Gomez, Baran, S. E., Conra, C. D. The effects of chronic stress on hippocampal morphology and function: An evaluation of chronic restraint paradigms. Brain Research, 2007, 1161: 56-64.
[15]
Xu, P., Wang, K. Z., Lu, C., Dong, L. M., Chen, Y. X., Wang, Q., Shi, Z., Yang, Y. Y., Chen, S. G., Liu, X. M. Effects of the chronic restraint stress induced depression on reward-related learning in rats. Behavioural Brain Research, 2017, 321: 185-192.
[16]
Willner, P., Towell, A., Sampson, D., Sopholeous, S., Muscat, R. Reduction of sucrose preference by chronic unpredictable mild stress, and its restoration by a tricyclic antidepressant. Psychopharmacology, 1987, 93: 358-364.
[17]
Willner, P. Chronic mild stress (CMS) revisited: Consistency and behavioural-neurobiological concordance in the effects of CMS. Neuropsychobiology, 2005, 52(2): 90-110.
[18]
Svitlana, A., Bijata, M., Ponimaskin, E., Wlodarczyk, J. Chronic unpredictable mild stress for modeling depression in rodents: Meta-analysis of model reliability. Neuroscience and biobehavioral reviews, 2018, 99: 101-116.
[19]
Burstein, O., Doron, R. The unpredictable chronic mild stress protocol for inducing anhedonia in mice. Journal of Visualized Experiments, 2018. .
[20]
Sapolsky, R. M. The influence of social hierarchy on primate health. Science, 2005, 308(5722): 648-652.
[21]
Kudryavtseva, N. N., Bakshtanovskaya, I. V., Koryakina, L. A. Social model of depression in mice of C57BL/6J strain. Pharmacology Biochemistry and Behavior, 1991, 38(2): 315-320.
[22]
Berton, O. Essential role of BDNF in the mesolimbic dopamine pathway in social defeat stress. Science, 2006, 311(5762): 864-868.
[23]
Golden, S. A., Covington, H. E., Berton, O., Russo, S. J. A standardized protocol for repeated social defeat stress in mice. Nature Protocols, 2011, 6(8): 1183-1191.
[24]
Czéh, B., Fuchs, E., Wiborg, O., Simon, M. Animal models of major depression and their clinical implications. Progress in Neuro-Psychopharmacology and Biological Psychiatry, 2016, 64: 293-310.
[25]
Seligman, M. P. Learned helplessness. Annual Review of Medicine, 1972, 23(1): 407-412.
[26]
Gururajan, A., Reif, A., Cryan, J. F., Slattery, D. A. The future of rodent models in depression research. Nature Reviews Neuroscience, 2019, 20(11): 686-701.
[27]
Willner, P. Validation criteria for animal models of human mental disorders: Learned helplessness as a paradigm case. Progress in Neuro-Psychopharmacology & Biological Psychiatry, 1986, 10(6): 677-690.
[28]
Porsolt, R. D., Anton, G., Blavet, N., Jalfre, M. Behavioural despair in rats: A new model sensitive to antidepressant treatments. European Journal of Pharmacology, 1978, 47(4): 379-391.
[29]
Yu, H. Y., Yin, Z. J., Yang, S. J., Ma, S. P., Qu, R. Baicalin reverses depressive-like behaviours and regulates apoptotic signalling induced by olfactory bulbectomy. Phytotherapy Research, 2016, 30(3): 469-475.
[30]
Farzin, D., Mansouri, N. Antidepressant-like effect of harmane and other beta-carbolines in the mouse forced swim test. European Neuropsychopharmacology: the Journal of the European College of Neuropsychopharmacology, 2006, 16(5): 324-328.
[31]
McArthur, R., Borsini, F. Animal models of depression in drug discovery: A historical perspective. Pharmacology Biochemistry and Behavior, 2006, 84(3): 436-452.
[32]
Flint, J., Kendler, K. S. The genetics of major depression. Neuron, 2014, 81(5): 1214.
[33]
Guffanti, G., Gameroff, M. J., Warner, V., Talati, A., Glatt, C. E., Wickramaratne, P., Weissman, M. M. Heritability of major depressive and comorbid anxiety disorders in multi-generational families at high risk for depression. American Journal of Medical Genetics Part B: Neuropsychiatric Genetics, 2016, 171(8): 1072-1079.
[34]
Corfield, E. C., Yang, Y., Martin, N. G., Nyholt, D. R. A continuum of genetic liability for minor and major depression. Translational Psychiatry, 2017, 7(5): e1131.
[35]
Boyle, E. A., Li, Y. I., Pritchard, J. K. An expanded view of complex traits: From polygenic to omnigenic. Cell, 2017, 169(7): 1177-1186.
[36]
Nishi, K., Kanemaru, K., Diksic, M. A genetic rat model of depression, Flinders sensitive line, has a lower density of 5-HT1A receptors, but a higher density of 5-HT1B receptors, compared to control rats. Neurochemistry International, 2009, 54(5-6): 299-307.
[37]
Solberg, L. C., Olson, S. L., Turek, F. W., Redei, E. Altered hormone levels and circadian rhythm of activity in the WKY rat, a putative animal model of depression. American Journal of Physiology-Regulatory, Integrative and Comparative Physiology, 2001, 281(3): R786-R794.
[38]
Rezvani, A. H., Parsian, A., Overstreet, D. H. The Fawn-Hooded (FH/Wjd) rat: A genetic animal model of comorbid depression and alcoholism. Psychiatric Genetics, 2002, 12(1): 1-16.
[39]
Sorge, R. E., Martin, L. J., Isbester, K. A., Sotocinal, S. G., Rosen, S., Tuttle, A. H., Wieskopf, J. S., Acland, E. L., Dokova, A., Kadoura, B. et al. Olfactory exposure to males, including men, causes stress and related analgesia in rodents. Nature Methods, 2014, 11(6): 629-632.
[40]
Covington, H. E., Lobo, M. K., Maze, I., Vialou, V., Hyman, J. M., Zaman, S., LaPlant, Q., Mouzon, E., Ghose, S., Tamminga, C. A. et al. Antidepressant effect of optogenetic stimulation of the medial prefrontal cortex. Journal of Neuroscience, 2010, 30(48): 16082-16090.
[41]
Bagot, R. C., Parise, E. M., Peña, C. J., Zhang, H. X., Maze, I., Chaudhury, D., Persaud, B., Cachope, R., Bolaños-Guzmán, C. A., Cheer, J. F. et al. Ventral hippocampal afferents to the nucleus accumbens regulate susceptibility to depression. Nature Communications, 2015, 6(1): 1-9.
[42]
Vialou, V., Bagot, R. C., Cahill, M. E., Ferguson, D., Robison, A. J., Dietz, D. M., Fallon, B., Mazei-Robison, M., Ku, S. M., Harrigan, E. et al. Prefrontal cortical circuit for depression- and anxiety-related behaviors mediated by cholecystokinin: Role of FosB. Journal of Neuroscience, 2014, 34(11): 3878-3887.
[43]
Rahman, M. M., Shukla, A. Chattarji, S. Extinction recall of fear memories formed before stress is not affected despite higher theta activity in the amygdala. eLife, 2018, 7: e35450.
[44]
Cho, J. H., Deisseroth, K., Bolshakov, V. Y. Synaptic encoding of fear extinction in mPFC-amygdala circuits. Neuron, 2013, 80(6): 1491-1507.
[45]
Park, K., Chung, C. Differential alterations in cortico-amygdala circuitry in mice with impaired fear extinction. Molecular Neurobiology, 2020, 57(2): 710-721.
[46]
Park, K., Chung, C. Differential alterations in cortico-amygdala circuitry in mice with impaired fear extinction. Molecular Neurobiology, 2020, 57(2): 710-721.
[47]
Liu, W. Z., Zhang, W. H., Zheng, Z. H., Zou, J. X., Liu, X. X., Huang, S. H., You, W. J., He, Y., Zhang, J. Y., Wang, X. D. et al. Identification of a prefrontal cortex-to-amygdala pathway for chronic stress-induced anxiety. Nature Communications, 2020, 11(1): 1-15.
[48]
Hiser, J., Koenigs, M. The multifaceted role of the ventromedial prefrontal cortex in emotion, decision making, social cognition, and psychopathology. Biological Psychiatry, 2018, 83(8): 638-647.
[49]
Jovanovic, T., Norrholm, S. D. Neural mechanisms of impaired fear inhibition in posttraumatic stress disorder. Frontiers in Behavioral Neuroscience, 2011, 5: 44. .
[50]
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. A prefrontal cortex-brainstem neuronal projection that controls response to behavioural challenge. Nature, 2012, 492(7429): 428-432.
[51]
Challis, C., Beck, S. G., Berton, O. Optogenetic modulation of descending prefrontocortical inputs to the dorsal raphe bidirectionally bias socioaffective choices after social defeat. Frontiers in Behavioral Neuroscience, 2014, 8: 43. .
[52]
Challis, C., Boulden, J., Veerakumar, A., Espallergues, J., Vassoler, F. M., Pierce, R. C., Beck, S. G., Berton, O. Raphe GABAergic neurons mediate the acquisition of avoidance after social defeat. Journal of Neuroscience, 2013, 33(35): 13978-13988.
[53]
Kim, J. J., Diamond, D. M. The stressed hippocampus, synaptic plasticity and lost memories. Nature Reviews Neuroscience, 2002, 3(6): 453-462.
[54]
MacQueen, G. M., Campbell, S., McEwen, B. S., MacDonald, K., Amano, S., Joffe, R. T., Nahmias, C., Young, L. T. Course of illness, hippocampal function, and hippocampal volume in major depression. PNAS, 2003, 100(3): 1387-1392.
[55]
Bagot, R. C., Parise, E. M., Peña, C. J., Zhang, H. X., Maze, I., Chaudhury, D., Persaud, B., Cachope, R., Bolaños-Guzmán, C. A., Cheer, J. F. et al. Ventral hippocampal afferents to the nucleus accumbens regulate susceptibility to depression. Nature Communications, 2015, 6(1): 1-9.
[56]
Carreno, F. R., Donegan, J. J., Boley, A. M., Shah, A., DeGuzman, M., Frazer, A., Lodge, D. J. Activation of a ventral hippocampus-medial prefrontal cortex pathway is both necessary and sufficient for an antidepressant response to ketamine. Molecular Psychiatry, 2016, 21(9): 1298-1308.
[57]
Liu, X., Ramirez, S., Pang, P. T., Puryear, C. B., Govindarajan, A., Deisseroth, K., Tonegawa, S. Optogenetic stimulation of a hippocampal engram activates fear memory recall. Nature, 2012, 484(7394): 381-385.
[58]
Ramirez, S., Liu, X., Lin, P. A., Suh, J., Pignatelli, M., Redondo, R. L., Ryan, T. J., Tonegawa, S. Creating a false memory in the hippocampus. Science, 2013, 341(6144): 387-391.
[59]
Ramirez, S., Liu, X., MacDonald, C. J., Moffa, A., Zhou, J., Redondo, R. L., Tonegawa, S. Activating positive memory engrams suppresses depression-like behaviour. Nature, 2015, 522(7556): 335-339.
[60]
Schultz, W., Dayan, P., Montague, P. R. A neural substrate of prediction and reward. Science, 1997, 275(5306): 1593-1599.
[61]
Kaufling, J. Alterations and adaptation of ventral tegmental area dopaminergic neurons in animal models of depression. Cell and Tissue Research, 2019, 377(1): 59-71.
[62]
Holly, E. N., Miczek, K. A. Ventral tegmental area dopamine revisited: Effects of acute and repeated stress. Psychopharmacology, 2016, 233(2): 163-186.
[63]
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. Molecular adaptations underlying susceptibility and resistance to social defeat in brain reward regions. Cell, 2007, 131(2): 391-404.
[64]
Cao, J. L., Covington, H. E., Friedman, A. K., Wilkinson, M. B., Walsh, J. J., Cooper, D. C., Nestler, E. J., Han, M. H. Mesolimbic dopamine neurons in the brain reward circuit mediate susceptibility to social defeat and antidepressant action. Journal of Neuroscience, 2010, 30(49): 16453-16458.
[65]
Chaudhury, D., Walsh, J. J., Friedman, A. K., Juarez, B., Ku, S. M., Koo, J. W., Ferguson, D., Tsai, H. C., Pomeranz, L., Christoffel, D. J. et al. Rapid regulation of depression-related behaviours by control of midbrain dopamine neurons. Nature, 2013, 493(7433): 532-536.
[66]
Tye, K. M., Mirzabekov, J. J., Warden, M. R., Ferenczi, E. A., Tsai, H. C., Finkelstein, J., Kim, S. Y., Adhikari, A., Thompson, K. R., Andalman, A. S. et al. Dopamine neurons modulate neural encoding and expression of depression-related behaviour. Nature, 2013, 493(7433): 537-541.
[67]
Friedman, A. K., Walsh, J. J., Juarez, B., Ku, S. M., Chaudhury, D., Wang, J., Li, X., Dietz, D. M., Pan, N., Vialou, V. F. et al. Enhancing depression mechanisms in midbrain dopamine neurons achieves homeostatic resilience. Science, 2014, 344(6181): 313-319.
[68]
Friedman, A. K., Walsh, J. J., Juarez, B., Ku, S. M., Chaudhury, D., Wang, J., Li, X., Dietz, D. M., Pan, N., Vialou, V. F. et al. Enhancing depression mechanisms in midbrain dopamine neurons achieves homeostatic resilience. Science, 2014, 344(6181): 313-319.
[69]
Walsh, J. J., Friedman, A. K., Sun, H. S., Heller, E. A., Ku, S. M., Juarez, B., Burnham, V. L., Mazei-Robison, M. S., Ferguson, D., Golden, S. A. et al. Stress and CRF gate neural activation of BDNF in the mesolimbic reward pathway. Nature Neuroscience, 2014, 17(1): 27-29.
[70]
Walsh, J. J., Friedman, A. K., Sun, H. S., Heller, E. A., Ku, S. M., Juarez, B., Burnham, V. L., Mazei-Robison, M. S., Ferguson, D., Golden, S. A. et al. Stress and CRF gate neural activation of BDNF in the mesolimbic reward pathway. Nature Neuroscience, 2014, 17(1): 27-29.
[71]
Wook Koo, J., Labonté, B., Engmann, O., Calipari, E. S., Juarez, B., Lorsch, Z., Walsh, J. J., Friedman, A. K., Yorgason, J. T., Han, M. H. et al. Essential role of mesolimbic brain-derived neurotrophic factor in chronic social stress-induced depressive behaviors. Biological Psychiatry, 2016, 80(6): 469-478.
[72]
Holtmaat, A., Svoboda, K. Experience-dependent structural synaptic plasticity in the mammalian brain. Nature Reviews Neuroscience, 2009, 10(9): 647-658.
[73]
Sousa, N., Almeida, O. F. X. Disconnection and reconnection: The morphological basis of (mal)adaptation to stress. Trends in Neurosciences, 2012, 35(12): 742-751.
[74]
Mitra, R., Adamec, R., Sapolsky, R. Resilience against predator stress and dendritic morphology of amygdala neurons. Behavioural Brain Research, 2009, 205(2): 535-543.
[75]
Zhang, J. Y., Liu, T. H., He, Y., Pan, H. Q., Zhang, W. H., Yin, X. P., Tian, X. L., Li, B. M., Wang, X. D., Holmes, A. et al. Chronic stress remodels synapses in an amygdala circuit-specific manner. Biological Psychiatry, 2019, 85(3): 189-201.
[76]
Gourley, S. L., Swanson, A. M., Koleske, A. J. Corticosteroid-induced neural remodeling predicts behavioral vulnerability and resilience. Journal of Neuroscience, 2013, 33(7): 3107-3112.
[77]
Johnson, S. A., Wang, J. F., Sun, X., McEwen, B. S., Chattarji, S., Young, L. T. Lithium treatment prevents stress-induced dendritic remodeling in the rodent amygdala. Neuroscience, 2009, 163(1): 34-39.
[78]
Phillips, A. G., Ahn, S., Howland, J. G. Amygdalar control of the mesocorticolimbic dopamine system: Parallel pathways to motivated behavior. Neuroscience & Biobehavioral Reviews, 2003, 27(6): 543-554.
[79]
Phelps, E. A., Delgado, M. R., Nearing, K. I., LeDoux, J. E. Extinction learning in humans: Role of the amygdala and vmPFC. Neuron, 2004, 43(6): 897-905.
[80]
McEwen, B. S., de Kloet, E. R., Rostene, W. Adrenal steroid receptors and actions in the nervous system. Physiological Reviews, 1986, 66(4): 1121-1188.
[81]
Yizhar, O., Klavir, O. Reciprocal amygdala-prefrontal interactions in learning. Current Opinion in Neurobiology, 2018, 52: 149-155.
[82]
Wellman, C. L., Izquierdo, A., Garrett, J. E., Martin, K. P., Carroll, J., Millstein, R., Lesch, K. P., Murphy, D. L., Holmes, A. Impaired stress-coping and fear extinction and abnormal corticolimbic morphology in serotonin transporter knock-out mice. Journal of Neuroscience, 2007, 27(3): 684-691.
[83]
Andolina, D., Maran, D., Valzania, A., Conversi, D., Puglisi-Allegra, S. Prefrontal/amygdalar system determines stress coping behavior through 5-HT/GABA connection. Neuropsychopharmacology, 2013, 38(10): 2057-2067.
[84]
Andolina, D., Maran, D., Viscomi, M. T., Puglisi-Allegra, S. Strain-dependent variations in stress coping behavior are mediated by a 5-HT/GABA interaction within the prefrontal corticolimbic system. International Journal of Neuropsychopharmacology, 2015, 18(3): pyu074.
[85]
Sutherland, R. J. The dorsal diencephalic conduction system: A review of the anatomy and functions of the habenular complex. Neuroscience & Biobehavioral Reviews, 1982, 6(1): 1-13.
[86]
Hu, H., Cui, Y., Yang, Y. Circuits and functions of the lateral habenula in health and in disease. Nature Reviews Neuroscience, 2020, 21(5): 277-295.
[87]
Lecourtier, L., Kelly, P. H. A conductor hidden in the orchestra? Role of the habenular complex in monoamine transmission and cognition. Neuroscience & Biobehavioral Reviews, 2007, 31(5): 658-672.
[88]
Shumake, J., Gonzalez-Lima, F. Brain systems underlying susceptibility to helplessness and depression. Behavioral and Cognitive Neuroscience Reviews, 2003, 2(3): 198-221.
[89]
Herkenham, M., Nauta, W. J. H. Efferent connections of the habenular nuclei in the rat. In: Neuroanatomy. Contemporary Neuroscientists (Selected Papers of Leaders in Brain Research). Boston: Birkhäuser, 1979.
[90]
Jhou, T. C., Geisler, S., Marinelli, M., Degarmo, B. A., Zahm, D. S. The mesopontine rostromedial tegmental nucleus: A structure targeted by the lateral habenula that projects to the ventral tegmental area of Tsai and substantia nigra compacta. The Journal of Comparative Neurology, 2009, 513(6): 566-596.
[91]
Aghajanian, G. K., Wang, R. Y. Habenular and other midbrain raphe afferents demonstrated by a modified retrograde tracing technique. Brain Research, 1977, 122(2): 229-242.
[92]
Yang, Y., Wang, H., Hu, J., Hu, H. L. Lateral habenula in the pathophysiology of depression. Current Opinion in Neurobiology, 2018, 48: 90-96.
[93]
Groenewegen, H. J., Ahlenius, S., Haber, S. N., Kowall, N. W., Nauta, W. J. H. Cytoarchitecture, fiber connections, and some histochemical aspects of the interpeduncular nucleus in the rat. The Journal of Comparative Neurology, 1986, 249(1): 65-102.
[94]
Zhang, J., Tan, L., Ren, Y., Liang, J., Lin, R., Feng, Q., Zhou, J., Hu, F., Ren, J., Wei, C. et al. Presynaptic Excitation via GABAB Receptors in Habenula Cholinergic Neurons Regulates Fear Memory Expression. Cell, 2016. 166(3): 716-728.
[95]
Stern, W. C., Johnson, A., Bronzino, J. D., Morgane, P. J. Effects of electrical stimulation of the lateral habenula on single-unit activity of raphe neurons. Experimental Neurology, 1979, 65(2): 326-342.
[96]
Baratta, M. V., Kodandaramaiah, S. B., Monahan, P. E., Yao, J., Weber, M. D., Lin, P. A., Gisabella, B., Petrossian, N., Amat, J., Kim, K. et al. Stress enables reinforcement-elicited serotonergic consolidation of fear memory. Biological Psychiatry, 2016, 79(10): 814-822.
[97]
Pandey, S., Shekhar, K., Regev, A., Schier, A. F. Comprehensive identification and spatial mapping of habenular neuronal types using single-cell RNA-seq. Current Biology, 2018, 28(7): 1052-1065.e7.
[98]
Cerniauskas, I., Winterer, J., de Jong, J. W., Lukacsovich, D., Yang, H., Khan, F., Peck, J. R., Obayashi, S. K., Lilascharoen, V., Lim, B. K., et al. Chronic stress induces activity, synaptic, and transcriptional remodeling of the lateral habenula associated with deficits in motivated behaviors. Neuron, 2019, 104(5): 899-915.e8.
[99]
Matsumoto, M., Hikosaka, O. Two types of dopamine neuron distinctly convey positive and negative motivational signals. Nature, 2009, 459(7248): 837-841.
[100]
Shumake, J., Edwards, E., Gonzalez-Lima, F. Opposite metabolic changes in the habenula and ventral tegmental area of a genetic model of helpless behavior. Brain Research, 2003, 963(1-2): 274-281.
[101]
Park, H., Rhee, J., Park, K., Han, J. S., Malinow, R., Chung, C. Exposure to stressors facilitates long-term synaptic potentiation in the lateral habenula. The Journal of Neuroscience, 2017, 37(25): 6021-6030.
[102]
Park, H., Rhee, J., Lee, S., Chung, C. Selectively impaired endocannabinoid-dependent long-term depression in the lateral habenula in an animal model of depression. Cell Reports, 2017, 20(2): 289-296.
[103]
Cui, Y., Yang, Y., Ni, Z., Dong, Y., Cai, G., Foncelle, A., Ma, S., Sang, K., Tang, S., Li, Y. et al. Astroglial Kir4.1 in the lateral habenula drives neuronal bursts in depression. Nature, 2018, 554(7692): 323-327.
[104]
Yang, Y., Cui, Y., Sang, K., Dong, Y., Ni, Z., Ma, S., Hu, H. Ketamine blocks bursting in the lateral habenula to rapidly relieve depression. Nature, 2018, 554(7692): 317-322.
[105]
Shelton, L., Pendse, G., Maleki, N., Moulton, E. A., Lebel, A., Becerra, L., Borsook, D. Mapping pain activation and connectivity of the human habenula. Journal of Neurophysiology, 2012, 107(10): 2633-2648.
[106]
Paulson, P. E., Morrow, T. J., Casey, K. L. Bilateral behavioral and regional cerebral blood flow changes during painful peripheral mononeuropathy in the rat. Pain, 2000, 84(2-3): 233-245.
[107]
Goto, M., Canteras, N. S., Burns, G., Swanson, L. W. Projections from the subfornical region of the lateral hypothalamic area. The Journal of Comparative Neurology, 2005, 493(3): 412-438.
[108]
Yu, L. C., Han, J. S. Habenula as a relay in the descending pathway from nucleus accumbens to periaqueductal grey subserving antinociception. The International Journal of Neuroscience, 1990, 54(3-4): 245-251.
[109]
Shelton, L., Becerra, L., Borsook, D. Unmasking the mysteries of the habenula in pain and analgesia. Progress in Neurobiology, 2012, 96(2): 208-219.
[110]
Cohen, S. R., Melzack, R. Morphine injected into the habenula and dorsal posteromedial thalamus produces analgesia in the formalin test. Brain Research, 1985, 359(1-2): 131-139.
[111]
Ma, Q. P., Shi, Y. S., Han, J. S. Further studies on interactions between periaqueductal gray, nucleus accumbens and habenula in antinociception. Brain Research, 1992, 583(1-2): 292-295.
[112]
Bhatnagar, S., Viau, V., Chu, A., Soriano, L., Meijer, O. C., Dallman, M. F. A cholecystokinin-mediated pathway to the paraventricular thalamus is recruited in chronically stressed rats and regulates hypothalamic-pituitary-adrenal function. The Journal of Neuroscience, 2000, 20(14): 5564-5573.
[113]
Hsu, D. T., Kirouac, G. J., Zubieta, J. K., Bhatnagar, S. Contributions of the paraventricular thalamic nucleus in the regulation of stress, motivation, and mood. Front Behav Neurosci, 2014, 8: 73.
[114]
Spencer, S. J., Fox, J. C., Day, T. A. Thalamic paraventricular nucleus lesions facilitate central amygdala neuronal responses to acute psychological stress. Brain Research, 2004, 997(2): 234-237.
[115]
Penzo, M. A., Robert, V., Tucciarone, J., De Bundel, D., Wang, M., Van Aelst, L., Darvas, M., Parada, L. F., Palmiter, R. D., He, M. et al. The paraventricular thalamus controls a central amygdala fear circuit. Nature, 2015, 519(7544): 455-459.
[116]
Zhang, Y., Liu, W., Lebowitz, E. R., Zhang, F., Hu, Y., Liu, Z., Yang, H., Wu, J., Wang, Y., Silverman, W. K. et al. Abnormal asymmetry of thalamic volume moderates stress from parents and anxiety symptoms in children and adolescents with social anxiety disorder. Neuropharmacology, 2020, 180: 108301.
[117]
Philip, N. S., Tyrka, A. R., Albright, S. E., Sweet, L. H., Almeida, J., Price, L. H., Carpenter, L. L. Early life stress predicts thalamic hyperconnectivity: A transdiagnostic study of global connectivity. Journal of Psychiatric Research, 2016, 79: 93-100.
[118]
Liao, M., Yang, F., Zhang, Y., He, Z., Song, M., Jiang, T., Li, Z., Lu, S., Wu, W., Su, L. et al. Childhood maltreatment is associated with larger left thalamic gray matter volume in adolescents with generalized anxiety disorder. PLoS One, 2013, 8(8): e71898.
[119]
Qin, S., Young, C. B., Duan, X., Chen, T., Supekar, K., Menon, V. Amygdala subregional structure and intrinsic functional connectivity predicts individual differences in anxiety during early childhood. Biological Psychiatry, 2014, 75(11): 892-900.
[120]
Babaev, O., Piletti Chatain, C., Krueger-Burg, D. Inhibition in the amygdala anxiety circuitry. Experimental & Molecular Medicine, 2018, 50(4): 1-16.
[121]
Do-Monte, F. H., Quiñones-Laracuente, K., Quirk, G. J. A temporal shift in the circuits mediating retrieval of fear memory. Nature, 2015, 519(7544): 460-463.
[122]
Christoffel, D. J., Golden, S. A., Walsh, J. J., Guise, K. G., Heshmati, M., Friedman, A. K., Dey, A., Smith, M. Rebushi, N., Pfau, M. et al. Excitatory transmission at thalamo-striatal synapses mediates susceptibility to social stress. Nature Neuroscience, 2015, 18(7): 962-964.
[123]
Zhu, Y., Wienecke, C. F., Nachtrab, G., Chen, X. A thalamic input to the nucleus accumbens mediates opiate dependence. Nature, 2016, 530(7589): 219-222.
[124]
Do-Monte, F. H., Minier-Toribio, A., Quiñones-Laracuente, K., Medina-Colón, E. M., Quirk, G. J. Thalamic regulation of sucrose seeking during unexpected reward omission. Neuron, 2017, 94(2): 388-400.e4.
[125]
Betley, J. N., Cao, Z. F., Ritola, K. D., Sternson, S. M. Parallel, redundant circuit organization for homeostatic control of feeding behavior. Cell, 2013, 155(6): 1337-1350.
[126]
Zhang, X., van den Pol, A. N. Rapid binge-like eating and body weight gain driven by zona incerta GABA neuron activation. Science, 2017, 356(6340): 853-859.
[127]
Giber, K., Diana, M. A., Plattner, V., Dugué, G. P., Bokor, H., Rousseau, C. V., Maglóczky, Z., Havas, L., Hangya, B., Wildner, H. et al. A subcortical inhibitory signal for behavioral arrest in the thalamus. Nature Neuroscience, 2015, 18(4): 562-568.
[128]
Halassa, M. M., Acsády, L. Thalamic inhibition: Diverse sources, diverse scales. Trends in Neuroscience, 2016, 39(10): 680-693.
[129]
Beas, B. S., Wright, B. J., Skirzewski, M., Leng, Y., Hyun, J. H., Koita, O., Ringelberg, N., Kwon, H. B., Buonanno, A., Penzo, M. A. The locus coeruleus drives disinhibition in the midline thalamus via a dopaminergic mechanism. Nature Neuroscience, 2018, 21(7): 963-973.
[130]
Miller, O. H., Bruns, A., Ammar, I. B., Mueggler, T., Hall, B. J. Synaptic regulation of a thalamocortical circuit controls depression-related behavior. Cell Reports, 2017. 20(8): 1867-1880.
[131]
Baek, J., Lee, S., Cho, T., Kim, S.-W., Kim, M., Yoon, Y., Kim, K. K., Byun, J., Kim, S. J., Jeong, J., Shin, H.-S. Neural circuits underlying a psychotherapeutic regimen for fear disorders. Nature, 2019, 566(7744): 339-343.
Publication history
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Publication history

Received: 12 February 2021
Revised: 21 April 2021
Accepted: 07 May 2021
Published: 25 June 2021
Issue date: December 2021

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© The Author(s) 2021

Acknowledgements

We thank all members of the Wu laboratory for discussion. This work was supported by the National Natural Science Foundation of China (Nos. 31770929 and 31522029 to H. W.), and the Beijing Municipal Science and Technology Commission (Nos. Z181100001518001 and Z161100000216154 to H. W.).

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