Talk abstracts

Talk on Tuesday 10:45-11:00am submitted by Chloe Page

DREADD-induced modulation of prefrontal parvalbumin cell activity has sex-specific effects on emotional behaviors

Chloe E Page (Neuroscience Graduate Program), Ryan Shepard (Department of Psychology, Ohio State University), Payton Hagerdorn (Department of Psychology, Ohio State University), Kelsey Heslin (Department of Psychology, Ohio State University), Laurence Coutellier (Department of Neuroscience, Department of Psychology, Ohio State University)

Abstract:
The prefrontal cortex (PFC) relies on a balance between excitatory and inhibitory neurotransmission for its functions, which includes emotional regulation. Parvalbumin (PV)-expressing cells are a subtype of inhibitory interneuron that are critical for regulating excitatory/inhibitory (E/I) balance and PFC-dependent behaviors. However, the role of PV cells in regulating emotional behaviors has not been extensively studied. We have previously shown that prefrontal PV (PFC-PV) cells are sensitive to chronic stress and increased expression of PV mRNA in the PFC correlates with increased emotionality in female, but not male, mice. Here we sought to determine how modulation of PFC-PV cell activity causes changes in emotional behaviors, and whether these effects vary by sex. To this end, we conducted a series of experiments using designer receptors exclusively activated by designer drugs (DREADDs) to control specifically the activity of PFC-PV cells. (1) We injected a Cre-dependent excitatory hM3DGq DREADD virus into the PFC of male and female PV:Cre mice and administered the DREADD ligand clozapine-N-oxide (CNO) 30 minutes prior to behavioral testing. Acute excitation of PFC-PV cells decreased depression-related behaviors in male mice but was otherwise insufficient to alter emotional behaviors. (2) We used the same excitatory DREADD virus and injected CNO once per day for 21 days. Chronic excitation of PFC-PV cells increased anxiety-related behaviors and reduced activity in the basomedial amygdala of females only. (3) We injected an inhibitory hM3DGi DREADD virus into the PFC and administered CNO 30 minutes prior to behavioral testing. Acute inhibition of PFC-PV cells reduced anxiety-related behaviors in females and depression-related behaviors in males. Acute PFC-PV cell inhibition also increased expression of activity-regulated cytoskeleton-associated protein (Arc) in females and decreased expression in males. Collectively, these findings support our previous research showing that PFC-PV cells regulate anxiety-related behaviors in females. These results also reveal a novel role for PFC-PV cells in acutely regulating depression-related behaviors in males. Future experiments will test if chronic inhibition of PFC-PV cells during or following UCMS is capable of rescuing emotional deregulations.

Keywords: chronic stress, parvalbumin, prefrontal cortex