Assistant Professor of Neurobiology
Stress, Social Isolation, PTSD, Neural Circuits of Emotion, Neuropeptides
Neural Circuits Underlying Psychogenic Stress
Under normal circumstances, stress and fear enable us to flexibly adapt to conditions in our environment, greatly contributing to our success and survival. However, in cases of prolonged or extreme psychogenic stress, this normally advantageous system can exert detrimental effects on the brain and behavior, giving rise to disturbances in mental health such as post-traumatic stress disorder, anxiety disorders, phobias, and social isolation. These disturbances can be extremely debilitating, targeting people regardless of age, sex, or ethnicity, and leading to increases in fear and violence in our society.
My lab is interested in understanding the brain circuits and neural mechanisms underlying various forms of stress. We apply cutting-edge, genetically-targeted molecular tools and techniques to identify, manipulate, and image from specific populations of neurons across a number of brain regions. We combine these techniques with in depth behavioral testing and computational analyses to dissect neural circuits and elucidate the role and function of particular cell populations within them.
Taking this molecular-behavioral approach, we ask questions such as how does the brain encode a single traumatic event? What does the brain look like after an extended period of social isolation? Can we target particular brain regions, cell populations, or signaling molecules to reverse the damaging effects of stress on behavior? In striving to answer these questions, we aim to better understand the brain and behavior, as well as potentially identify novel therapeutic targets for the treatment of mental health disorders.
References (Selected Publications)
- Zelikowsky M, Ding K, Anderson DJ. Neuropeptidergic control of an internal brain state produced by prolonged social isolation stress. Cold Spring Harb Symp Quant Biol (2019).
- Zelikowsky M, Hui M, Karigo T, Yang B, Blanco M, Beadle K, Gradinaru V, Deverman BE, Anderson DJ. The neuropeptide Tac2 controls a distributed brain state induced by chronic social isolation stress. Cell (2018).
- Remedios R*, Kennedy A*, Zelikowsky M, Grewe B, Schnitzer M, Anderson DJ. Social behaviour shapes hypothalamic neural ensemble representations of conspecific sex. Nature 550, 388–392 (2017).
- Kunwar P, Zelikowsky M, Remedios R, Cai H, Yilmaz M, Meister M, Anderson DJ. Ventromedial hypothalamic neurons control a defensive emotion state. eLife 4 (2015).
- Hong W, Kennedy A, Burgos-Artizzu XP, Zelikowsky M, Navonne SG, Perona P, Anderson DJ. Automated Measurement of Mouse Social Behaviors Using Depth Sensing, Video Tracking, and Machine Learning. Proceedings of the National Academy of Sciences 112, E5351-5360 (2015).
- Zelikowsky M, Chawla M, Hersman S, Barnes CA, Fanselow MS. Neuronal ensembles in amygdala, hippocampus and prefrontal cortex track differential components of contextual fear. Journal of Neuroscience 34, 8462-8466 (2014).
- Fanselow MS, Zelikowsky M, Perusini J, Rodriguez-Barrera V, & Hersman S. Isomorphisms between psychological processes and neural mechanisms: from stimulus elements to genetic markers of activity. Neurobiology of Learning and Memory 108, 5-13 (2014).
- Zelikowsky M, Bissiere S, Hast TA, Bennett RZ, Abdipranato A, Vissel B & Fanselow MS. Prefrontal microcircuit underlies contextual learning after hippocampal loss. Proceedings of the National Academy of Sciences 110, 9938-9943 (2013).
- Zelikowsky M, Hast TA, Bennett RZ, Merjanian M, Nocera, NA, Ponnusamy R, Fanselow MS. Cholinergic blockade frees fear extinction from its contextual dependency. Biological Psychiatry 73, 345-352 (2013).
- Zelikowsky M, Bissiere S, Fanselow, MS. Contextual fear memories formed in the absence of the dorsal hippocampus decay across time. Journal of Neuroscience 32, 3393-3397 (2012).
- Halladay L, Zelikowsky M, Blair HT, Fanselow MS. Reinstatement of extinguished fear by an unextinguished conditional stimulus. Frontiers in Behavioral Neuroscience 6, 18 (2012).
- Zelikowsky M, Pham, D, Fanselow, MS. Temporal factors control hippocampal contribution to fear renewal. Hippocampus 22, 1096-1106 (2012).
- Bissiere S, Zelikowsky M, Ponnusamy R, Jacobs NS, Blair HT, Fanselow MS. Electrical synapses control hippocampal contributions to fear learning and memory. Science 331, 87-91 (2011).
- Krasne, F, Fanselow, MS, Zelikowsky M. Design of a neurally plausible fear learning model. Frontiers in Behavioral Neuroscience 5, 41 (2011).
- Zelikowsky M & Fanselow MS. Conditional analgesia, negative feedback & error correction. Associative Learning and Conditioning: Human and Animal Applications (eds Schachtman TR & Reilly SS). Oxford University Press (2011).
- Zelikowsky M & Fanselow MS. Opioid regulation of Pavlovian overshadowing in fear conditioning. Behavioral Neuroscience 124, 510-519 (2010).
- Craske MG, Kircanski K, Zelikowsky M, Mystkowski J, Chowdhury N, Baker A. Optimizing inhibitory learning during exposure therapy. Behavioral Research and Therapy 46, 5-27 (2008).