Kristen Pleil

Hormones and neuropeptides are endogenous signaling molecules that are master regulators of adaptive behavior. They are highly conserved across mammalian species, and genetic/epigenetic variations that affect their expression and signaling are associated with many psychiatric diseases including anxiety, depression, and alcohol and substance use disorders. The Pleil lab uses converging in vivo and ex vivo approaches in mice to examine the signaling and circuit mechanisms by which these hormones and neuropeptides control neuropsychiatric disease-related behaviors through their effects on the anatomical organization and circuit function, as well as through their signaling interactions at membrane-bound receptors. Projects in the lab span different disease-related behaviors, from binge alcohol drinking and opioid intake to acute stress reactivity and reward/aversion, and they investigate the roles of a number of interacting brain circuits in the limbic system. Many lines of investigation including examination of plasticity in these mechanisms due to stress or alcohol/drug exposure in adulthood or during critical developmental periods including early postnatal development and adolescence. Examples of projects in the lab include 1) characterizing how the sex hormone estrogen produced in the ovaries rapidly signals via membrane-bound receptors on neuropeptidergic neurons to orchestrate their activity and role(s) in alcohol drinking and anxiety behavior in females; a related line of investigation examines chronic alcohol consumption recruits additional peripheral (non-ovarian) sources of estrogen to participate in this behavioral control in both males and females; 2) examining estrogen receptor-opioid peptide receptor signaling during learning about the rewarding/aversive effects of opioids and the context in which they are experienced; a related collaboration focuses on the relationship between synaptic and epigenetic plasticity during opioid learning; and 3) delineating how the thalamus controls adaptive behavioral responses to positive and negative environmental stimuli, including acute physiological stressors, differently in males and females through sex-dependent function and neuropeptide modulation of thalamic circuits. In all projects, the lab collaboratively strives to understand the brain circuit-specific signaling mechanisms by which hormones and neuropeptides regulate behavior and plasticity that contributes to neuropsychiatric diseases states.

Current Projects:

• Estrogen signaling regulation of alcohol drinking and anxiety
• Hormone modulation of thalamic control of stress responses
• Sex differences in opioid peptide regulation of neurotransmitter release
• Synaptic and epigenetic plasticity in opioid drug-context memory