Exploring whether learning and decision-making deficits caused by early life stress in mice translate to human patient groups.

Dimension learning tasks have offered insight into decision-making deficits in a variety of mental health conditions including OCD (Chamberlain et al., 2006; Purcell et al., 1998a, 1998b), schizophrenia (Wang, Hu, & Li., 2022), and several mood disorders (Gabrys et al., 2018; Purcell et al., 1998b). Research has begun to use mouse models to uncover the underlying neurobiology of dimension learning and its relationship to mental illness. This project aims to explore whether deficits observed in mice translate to human patients and whether computational modelling can be used to bridge the translational gap.

To explore this in mice, we will use an adolescent social isolation (ASI) paradigm. Socially isolated mice have been used as a model for several psychiatric phenotypes, including depressive-like behavior (Koike et al., 2009; Amiri et al., 2015b), social deficits (Koike et al., 2009; Okada et al., 2015) and anxiety behaviors (Ago et al., 2007; Amiri et al., 2015b). Additionally, we can probe dimension learning ability using an adaptation of the CANTAB intra-extra dimensional (IED) set-shifting task for mice (Owen et al., 1991, Garner et al., 2006). Recent work has shown that isolated mice fail to learn the relevant dimensions in this task and show significantly different behaviour relative to group-housed mice (Gregoriou et al., in prep). Additionally, using retrograde tracing and chemogenetic manipulations, they demonstrated that this deficit appears to be caused by reduced excitability in ventral-hippocampus to pre-frontal cortex projecting neurons (vH-PFC), providing a clear neuronal pathway to facilitate dimension learning. To explore this further, we will use single-unit recordings to establish whether individual neurons in the vH-PFC pathway appear to be representing the current relevant dimension during the task. By doing so, we hope to establish a clear neurobiological basis for dimension learning.