Spencer Fox Eccles School of Medicine
92 Social Effects of Corticotropin-Releasing Horomone and Tachykinin 2 Cells in the Bed Nucleus of the Stria Terminals
Nicholas Poll
Faculty Mentor: Moriel Zelikowsky (Neurobiology, University of Utah)
Social interaction is one of the chief drivers of evolution and natural selection. Animal interactions shape the ecological world and have shaped the world’s evolutionary timeline. Of the many types of animal interactions, one of the most influential to behavior and development is aggression. Many animals’ aggressive behaviors and mechanisms are so distinct that their origins can be traced back to specific selective pressures. These pressures range from reproductive competition to predator-prey interactions and have apparent effects on many species’ developments. Many stressors can increase aggressive tendencies found in mammals, yet it is clear that the neural bases that connect these stressors and their behavioral responses are understudied.
This project’s targeted brain region is the dorsal stria terminalis bed nucleus (dBNST). The BNST is a neurochemically diverse node of the extended amygdala that mediates stress and sensory information. It anatomically acts as a relay station between several structures, including the hypothalamus and amygdala. The BNST modulates stressor-induced aggressive behaviors; however, the neural mechanisms that connect this region and these behaviors are relatively understudied.
Corticotropin-releasing Hormone (CRH) in mammals displays upregulation following the introduction of a stressor and mediates aggression and anxiety. Similarly, tachykinin-expressing neurons have a role in mediating aggression in mammals. While CRH and tachykinin’s link to anxiety and aggression is well supported, it is not clear to what extent it has on dBNST. This project aims to provide data to support CRH and Tachykinin 2’s (Tac2) role in the dBNST mediating mouse aggression through optogenetic stimulation. Optogenetic stimulation of Tac2, CRH, and Tac2 ∩ CRH cells in the dBNST resulted in dissociable behaviors. These behaviors seem to follow a model for defensive response similar to the Predatory Immanence Continuum. The proposed model connects the targeted cell types in the dBNST to a range of defensive response behaviors found in social situations.
References
Delville, Y., De Vries, G. J., & Ferris, C. F. (2000). Neural Connections of the Anterior Hypothalamus and Agonistic Behavior in Golden Hamsters. Brain, Behavior and Evolution, 55(2), 53–76. https://doi.org/10.1159/000006642
Fanselow, M. S. (2022). Negative valence systems: Sustained threat and the predatory imminence continuum. Emerging Topics in Life Sciences, 6(5), 467–477. https://doi.org/10.1042/ETLS20220003
Fenster, R. J., Lebois, L. A. M., Ressler, K. J., & Suh, J. (2018). Brain circuit dysfunction in post- traumatic stress disorder: From mouse to man. Nature Reviews Neuroscience, 19(9), 535–551. https://doi.org/10.1038/s41583-018-0039-7
Flanigan, M. E., & Kash, T. L. (2022). Coordination of social behaviors by the bed nucleus of the stria terminalis. European Journal of Neuroscience, 55(9–10), 2404–2420. https://doi.org/10.1111/ejn.14991
Haller, J., Tóth, M., Halasz, J., & De Boer, S. F. (2006). Patterns of violent aggression-induced brain c-fos expression in male mice selected for aggressiveness. Physiology & Behavior, 88(1–2), 173– 182. https://doi.org/10.1016/j.physbeh.2006.03.030
Lukas, M., Toth, I., Reber, S. O., Slattery, D. A., Veenema, A. H., & Neumann, I. D. (2011). The Neuropeptide Oxytocin Facilitates Pro-Social Behavior and Prevents Social Avoidance in Rats and Mice. Neuropsychopharmacology, 36(11), 2159–2168. https://doi.org/10.1038/npp.2011.95
Matsumoto, K., Pinna, G., Puia, G., Guidotti, A., & Costa, E. (2005). Social isolation stress-induced aggression in mice: A model to study the pharmacology of neurosteroidogenesis. Stress, 8(2), 85–93, https://doi.org/10.1080/10253890500159022
Nordman, J. C., Ma, X., Gu, Q., Potegal, M., Li, H., Kravitz, A. V., & Li, Z. (2020a). Potentiation of Divergent Medial Amygdala Pathways Drives Experience-Dependent Aggression Escalation. The Journal of Neuroscience, 40(25), 4858–4880. https://doi.org/10.1523/JNEUROSCI.0370-20.2020
Nordman, J., Ma, X., & Li, Z. (2020b). Traumatic Stress Induces Prolonged Aggression Increase through Synaptic Potentiation in the Medial Amygdala Circuits. Eneuro, 7(4), ENEURO.0147- 20.2020. https://doi.org/10.1523/ENEURO.0147-20.2020
Stagkourakis, S., Spigolon, G., Williams, P., Protzmann, J., Fisone, G., & Broberger, C. (2018). A neural network for intermale aggression to establish social hierarchy. Nature Neuroscience, 21(6), 834–842. https://doi.org/10.1038/s41593-018-0153-x
Weber, E. M., Dallaire, J. A., Gaskill, B. N., Pritchett-Corning, K. R., & Garner, J. P. (2017).
Aggression in group-housed laboratory mice: Why can’t we solve the problem? Lab Animal, 46(4), 157–161. https://doi.org/10.1038/laban.1219
Yamaguchi, T. (2022). Neural circuit mechanisms of sex and fighting in male mice. Neuroscience Research, 174, 1–8. https://doi.org/10.1016/j.neures.2021.06.005
Zelikowsky, M., Hui, M., Karigo, T., Choe, A., Yang, B., Blanco, M. R., Beadle, K., Gradinaru, V., Deverman, B. E., & Anderson, D. J. (2018). The Neuropeptide Tac2 Controls a Distributed Brain State Induced by Chronic Social Isolation Stress. Cell, 173(5), 1265-1279.e19. https://doi.org/10.1016/j.cell.2018.03.037