Identifying neural substrates of resilience to stress

Mentor Areas

Our long term goal is to understand why some individuals are vulnerable or resilient to the potentially adverse effects of chronic stress. Chronic stress is a critical factor contributing to the development of affective and anxiety disorders and can precipitate relapse of depression and post-traumatic stress disorder. This intimate association between repeated/chronic stress and affective and anxiety disorders underscores the need to understand fully the neural circuitry that regulates the physiological and behavioral consequences of repeated stress. We approach this need in two ways, using rat models. First, we are examining the neural circuits that are impacted by stress exposure and how these circuits, in turn, produce dysfunction in physiology and behavior. In these studies, we use state-of-the-art neuroscience techniques, including multiplex PCR and protein arrays,optogenetic stimulation of peptide release, in situ hybridization, tract tracing, immunocytochemistry and western blots, as well as behavioral and pharmacological approaches that allow us to pinpoint the brain regions of interest and to identify specific neural mechanisms. We have used these technical approaches to examine specific cortico-limbic circuits important for regulating stress reactivity. We have found that neural adaptations to chronic stress develop over time and, once developed, are stable. Second, we examine individual differences in reactivity to stress to understand how some are vulnerable and others resistant to the effects of stress. We have observed that individual differences in how adult animals cope with defeat by a dominant animal have neural and behavioral repercussions. In addition, we have observed that prenatal and early postnatal environmental factors produce enduring effects on neural circuitry regulating stress reactivity. Recently, we have observed the stress of isolation during adolescence produces enduring effects on behavioral, neuroendocrine and neural reactivity to stress and these effects are more pronounced in females. In these developmental studies, we are collaborating to use emerging neuroimaging techniques to examine development of fiber tracts and gray matter in addition to the techniques mentioned above.

Description:

**Please note that the lab is currently full and will not be taking any additional undergraduates this Spring 2023**

The overall goal of our research is to understand how and why some individuals are vulnerable to the effects of stress and others are resistant to these effects. Using animal models, our lab studies the effects of repeated exposure to stressful stimuli on behavior and neuroendocrine and examines the neural circuits that regulate these responses to understand the neural substrates of stress resilience. We are also interested in how events taking place in early life can predispose individuals to the effects of stress. This research has relevance for understanding stressinduced psychiatric diseases and exacerbation of inflammatory bowel disease.

Current available projects include: 1) examining the effects of the neuropeptide Orexin in regulating behavior and stress responses 2) examining individual differences in responses to social defeat in rats and whether vulnerability to defeat can be reversed 3) examining the effects of social isolation stress in adolescence and the long-term impact of such stress on adult behavior and cognition 4) examining the mechanisms by which stress exacerbates inflammatory bowel disease.

Students will work under the supervision of a research assistant or graduate student, and will learn a variety of general laboratory procedures, including handling rats, behavioral testing, small animal surgical procedures, brain sectioning and standard histological techniques. Students will gather data, both neuroendocrine and behavioral, enter data into spreadsheets, analyze and graph data. Students will also participate in weekly lab meetings.

Preferred Qualifications

Some coursework in biology, biopsychology, neuroscience is required. Prerequisites include some introductory Neuroscience, Biology, Behavioral Neuroscience or related coursework.