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Cooke, Matthew Bannerman

University of British Columbia

In the quest for rewards, which can range from food to other incentives, both animals and humans must navigate the inherent uncertainties of their environments. The ability to learn from and adapt to these uncertainties, modifying cognitive strategies for reward acquisition, is crucial. This adaptive process is compromised in various neurological and psychological disorders, including depression, obsessive-compulsive disorder (OCD), Parkinson’s disease, schizophrenia, among others. Traditionally, research has focused on the orbitofrontal cortex (OFC), striatum, and amygdala in forming probabilistic reward associations. Since the hippocampus is a brain region heavily involved in the formation and retrieval of memory, and probabilistic reversal learning is a learning task, we hypothesized that the hippocampus is involved. Emerging evidence, including prior research from our laboratory, suggests that hippocampal neurogenesis plays a role in modulating reward feedback sensitivity, hinting at a more nuanced involvement of the hippocampus in this process. Given the hippocampus' extensive connections with the prefrontal cortex (PFC), amygdala, and striatum, we hypothesized that it might be a critical contributor to probabilistic learning mechanisms. The hippocampus itself is not a monolithic structure. It is differentiated into dorsal and ventral domains, with the dorsal primarily implicated in cognitive tasks such as spatial navigation and the ventral in encoding emotional significance. While historically considered in a dichotomous framework, contemporary studies indicate that both hippocampal regions engage in various learning and memory functions. We employed both pharmacological and chemogenetic techniques to transiently inactivate the dorsal and ventral hippocampus. Pharmacological inactivation yielded observable effects in both regions. Chemogenetic inactivation of the dorsal hippocampus did not yield notable results. However, there were discernible and significant differences between the adeno- associated virus (AAV) treated and control groups. These findings may shed light on the differentiated, yet interrelated, roles of hippocampal regions in learning under uncertainty. Our research demonstrates that pharmacological inactivation of the dorsal and ventral hippocampus lead to changes in perseverative behaviours, deemed Win-Stay, as well as impulsivity. Furthermore, chemogenetic inactivation shows diffuse effects of DREADD treatment versus non-surgical controls. AAV surgery leads to a decrease in performance measures (total reversals) as well as perseverative behaviour.

Text

2024-04-29

Attribution-NonCommercial-NoDerivatives 4.0 International

http://hdl.handle.net/2429/88060

Neuroscience

University of British Columbia

UBCV

http://creativecommons.org/licenses/by-nc-nd/4.0/