Neural Circuitry of Fear and Anxiety
Fear is a highly conserved emotion with specific behavioral expressions. A great deal has been learned about the brain structures involved in processing learned (conditioned) fear, such as the anatomic subdivisions of the amygdala, but much less is known about the neuronal microcircuits that control fear within those brain structures. Using molecular markers for specific neuronal subtypes, and optogenetic and pharmacogenetic manipulations of neuronal activity as well as virally based tools for mapping neural connectivity, we are elucidating the structure and function of brain microcircuits that control fear. We are carrying out such investigations in both the amygdala, and in other, less explored areas such as the lateral septum. We are interested in how circuits for learned fear are related to those that control innate fear, as well to those that control anxiety. An elucidation of neural circuits for fear and anxiety should provide a cellular platform for understanding how genes, drugs and experience act on and modify these circuits, in both normal behavior and in affective disorders such as anxiety and depression, and may lead to the identification of novel candidate drug targets for these disorders.
Kennedy, A., Kunwar, P.S., Li, L.-Y., Stagkourakis, S., Wagenaar, D.A., and Anderson, D.J. (2020). Stimulus-specific hypothalamic encoding of a persistent defensive state. Nature 586, 730–734.
Zelikowsky, M., Hui, M., Karigo, T., Choe, A., Yang, B., Blanco, M.R., Beadle, K., Gradinaru, V., Deverman, B.E., and Anderson, D.J. (2018). The Neuropeptide Tac2 Controls a Distributed Brain State Induced by Chronic Social Isolation Stress. Cell 173, 1265–1279.e19.
Kunwar, P.S., Zelikowsky, M., Remedios, R., Cai, H., Yilmaz, M., Meister, M., and Anderson, D.J. (2015). Ventromedial hypothalamic neurons control a defensive emotion state. Elife 4, e06633.
Gibson, W.T., Gonzalez, C.R., Fernandez, C., Ramasamy, L., Tabachnik, T., Du, R.R., Felsen, P.D., Maire, M.R., Perona, P., and Anderson, D.J. (2015). Behavioral Responses to a Repetitive Visual Threat Stimulus Express a Persistent State of Defensive Arousal in Drosophila. Curr Biol 25, 1401–1415.
Anthony, T. E., Dee, N., Bernard, A., Lerchner, W., Heintz, N., & Anderson, D. J. (2014). Control of stress-induced persistent anxiety by an extra-amygdala septohypothalamic circuit. Cell, 156(3), 522–536
Haubensak, W., Kunwar, P.S., Cai, H., Ciocchi, S., Wall, N.R., Ponnusamy, R., Biag, J., Dong, H.W., Deisseroth, K., Callaway, E.M., et al. (2010). Genetic dissection of an amygdala microcircuit that gates conditioned fear. Nature 468, 270-276. [PubMed]