Project 467202

The prevalence of social isolation stress (SIS) has been recognized within the context of the COVID-19 pandemic, correctional institutions, and declining in-person socializations. SIS is known to induce changes in social behaviors, such as increased aggression, and poor social memory. The cellular and network changes that emerge in the brain following SIS have not been well studied. As such, the hippocampal cornu ammonis region 2 (CA2) is of interest as the activity of excitatory CA2 pyramidal cells play an essential role in social recognition memory. My preliminary data have shown that social memory deficits in SIS mice arise together with decreased CA2 activity, as measured using immunohistochemistry for c-Fos (an early gene that estimates neural activity). My thesis work will attempt to further elucidate the effect SIS has on cellular organization and CA2 activity through two key methods. First, I will use electrophysiology to record excitatory and inhibitory neural activity within the CA2. Firing rate and activity patterns of these cells will be recorded following presentation of both novel and familiar mice. It is hypothesized that SIS mice will exhibit decreased firing rate upon novel mice presentation. Second, I plan to use pharmacogenetics to transduce CA2 pyramidal neurons with a designer receptor exclusively activated by designer drugs (DREADD) to modulate the activity of CA2 during SIS. This approach will allow me to increase the activity of these neurons during isolation and determine if social memory impairments can be restored in SIS mice. These projects will provide an essential first step to understand how the brain is disrupted in SIS, and will help guide effective future behavioural/neuropharmacological treatments to alleviate SIS associated symptoms.