FUNCTIONAL DISSECTION OF MEDIODORSAL THALAMUS SUBDIVISIONS IN SOCIAL BEHAVIOR

The mediodorsal thalamus (MD) is a higher-order thalamic nucleus with extensive connections to cortical and subcortical regions. Its interactions with the prefrontal cortex (PFC) and anterior cingulate cortex (ACC), key regions involved in social and cognitive behavior, suggest a central role for the MD in higher-order social processes. Although often studied as a single structure, the functional contributions of its distinct subdivisions remain largely unexplored, particularly in social behavior. In this study, adult male and female Swiss albino mice received bilateral excitotoxic lesions selectively targeting either the lateral (MDL) or mediocentral (MDmc) subdivisions of the MD using N-methyl-D-aspartate (NMDA). Behavioral outcomes were assessed using the open field, elevated plus maze, social memory, social dominance, and three-chamber social tests. Lesions in both MDL and MDmc increased anxiety-like behavior, reduced locomotor activity, and induced hypoactivity. Both lesions impaired sociability and preference for social novelty; however, MDmc lesions produced more pronounced deficits in social recognition memory and social novelty discrimination, particularly in females during repeated social exposure. Social dominance remained largely unaffected. These findings indicate that MD subdivisions contribute differentially to social cognition, with MDmc playing a key role in social memory and novelty recognition. Given the conserved connectivity of the MD with prefrontal networks, these results may provide insight into neural mechanisms underlying social and cognitive deficits observed in neuropsychiatric disorders, including schizophrenia and autism spectrum disorder.