LATERALISED NEURONAL NETWORKS OF REWARD SEEKING ACROSS MOUSE LIFESPAN

Reward seeking behaviors are supported by distributed neuronal networks that functional organisation evolves throughout aging. The aim of this study is to investigate how lateralised neural circuits underlying reward seeking are shaped across mouse lifespan.
Understanding age-dependent differences in neuronal basis of behavior is crucial for elucidating the mechanisms underlying cognitive decline and age-related neurological disorders. This study investigates neuronal networks of social learning in mice across different age groups using IntelliCage automated behavioral system, whole brain iDISCO clearing coupled with c-Fos immunostaining and chemogenetic manipulations.
We observed significant variations in behavior between young (3-5 months old) and old (>18 months old) mice, particularly in exploratory activity, social behaviors, learning and memory tasks.
Further, iDISCO analysis revealed age-related differences in the activation patterns of brain regions associated with olfactory and cognitive functions. In particular, we observed strong lateralization of old mice brain activity in hippocampal and amygdalar areas. This phenomenon was much less pronounced in young animals. Chemogenetic manipulations confirmed specific engagement of the left, but not right, medial nucleus of the amygdala in social preference and learning again only in old, but not young, mice.
Our study demonstrates that spontaneous behavioral strategies employed by mice in order to find reward change as animals age, and this process is accompanied by evolving brain network activity. In particular, we show for the first time that mouse brain activity is strongly lateralised and this process progresses over time.