Cooper Behavioral Neuroscience Laboratory
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    • Society for Neuroscience, 2019 >
      • Clarity et al., 2019; Society for Neuroscience 2019
      • Grizzell et al., 2019; Society for Neuroscience, 2019
    • Gordon Amygdala Conference: 2019 >
      • Grizzell et al., 2019 - Gordon Research Conference: The Amygdala
    • Society for Behavioral Neuroendocrinology, 2019 >
      • Cannon et al., 2019, Society for Behavioral Neuroendocrinology
      • Grizzell et al., 2019, Society for Behavioral Neuroendocrinology
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Research

Conditioned Defeat Model

We use a social defeat model in Syrian hamsters to investigate the cellular and molecular mechanisms controlling stress-induced changes in behavior. In our model, hamsters are exposed to a brief social defeat in the home cage of a larger, more aggressive opponent and, the next day, are tested in their own home cage with a smaller, non-aggressive opponent. At testing subjects fail to display normal territorial aggression and instead show increased submissive and defensive behavior and social avoidance. This stress-induced change in behavior is called the conditioned defeat response and is used to study the biological basis of stress-related mental illness including post-traumatic stress disorder (PTSD).

Project 1: Identifying neural circuits that promote resistance to social stress

We have tested hamsters with established dominance relationships in our conditioned defeat model and found that dominant individuals show a reduced conditioned defeat response compared to subordinates. Also, we found that dominants show increase c-Fos immunoreactivity (i.e. neural activation) in the ventral medial prefrontal cortex (vmPFC) compared to subordinates. We have several ongoing studies aimed at understanding the neural circuits controlling resistance to conditioned defeat in dominant hamsters. We are using neural tract tracing techniques to test whether dominant hamsters selectively activate neurons in the vmPFC that send axonal projections to the basolateral amygdala (BLA) and/or the dorsal raphe nucleus (DRN). Also, we are using chemogenetics (i.e. DREADDs) to test whether selective inhibition of a vmPFC-to-BLA neural circuit or a vmPFC-to-DRN neural circuit prevents resistance to conditioned defeat in dominant hamsters. The goal if this line of research is to advance our understanding of the mechanisms by which the medial prefrontal cortex coordinates top-down regulation of emotion and promotes coping with stressful events. 

Funded by a R15 grant from National Institute of Mental Health


Project 2: Understanding the neural plasticity that supports stress resistance in dominant animals

We have shown that dominant hamsters gradually develop resistance to conditioned defeat during the 2-week maintenance of their dominance relationship. We are particularly interested in the neural plasticity that occurs during the maintenance of dominance relationships that supports resistance to conditioned defeat. We have shown that dominant hamsters exhibit a surge in plasma testosterone and an up-regulation of androgen receptors in the medial amygdala (MeA) after winning agonistic encounters. Also, pharmacological blockade of androgen receptors prevents both the up-regulation of MeA androgen receptors and resistance to conditioned defeat in dominant hamsters.  These results suggest that winning aggressive encounters promotes resistance to social stress by enhancing testosterone activity at androgen receptors in select brain regions. We are pursuing the mechanisms by which androgen receptor activity in the MeA promotes resistance to conditioned defeat.

Funded by a R21 grant from National Institute of Mental Health


Project 3: Identifying the mechanisms by which alcohol consumption modulates vulnerability to social stress

We have developed an acute social defeat model in mice in which three consecutive defeat episodes lead to increased social avoidance. Brain-derived neurotrophic factor (BDNF) is a molecule known to be critical for synaptic plasticity and experience-dependent changes in behavior. We have shown that the enzymatic conversion of proBDNF into mature BDNF within the BLA is necessary for the consolidation of defeat-related memories. Interestingly, about one-third of mice fail to exhibit defeat-induced social avoidance and are considered resistant to social stress. Because of the comorbidity of stress-related mental illness and alcohol abuse, we are interested in the mechanisms by which alcohol consumption may alter vulnerability to the effects of acute social defeat stress in mice. This project is performed in collaboration with Dr. Rebecca Prosser’s lab in the Department of Biochemistry Cellular and Molecular Biology.

Funded by a NARSAD Young Investigator Award from the Brain & Behavior Research Foundation


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  • Home
  • Research
  • People
  • Photos
  • Presentations
    • Society for Neuroscience, 2019 >
      • Clarity et al., 2019; Society for Neuroscience 2019
      • Grizzell et al., 2019; Society for Neuroscience, 2019
    • Gordon Amygdala Conference: 2019 >
      • Grizzell et al., 2019 - Gordon Research Conference: The Amygdala
    • Society for Behavioral Neuroendocrinology, 2019 >
      • Cannon et al., 2019, Society for Behavioral Neuroendocrinology
      • Grizzell et al., 2019, Society for Behavioral Neuroendocrinology
  • Publications
  • SfN Chapter
  • Links