108 | Medial prefrontal cortex altered encoding of contextual information in a schizophrenia mouse model

Cognition, Behavior, and Memory

Author: Javier Gonzalez Sanabria | Email: javiergs89@gmail.com

Javier Gonzalez Sanabria , María Florencia Santos , Juan Emilio Belforte , Camila Zold

1° Grupo de Neurociencia de Sistemas, Instituto de Fisiología y Biofísica, IFIBIO-Houssay, UBA-CONICET.

The medial prefrontal cortex (mPFC) forms adaptable complex contextual representations that include spatial and emotional elements to guide goal-directed behaviors. Altered mPFC activity has been associated with the cognitive deficits observed in schizophrenia (SZ). However, it is still unclear how mPFC neurons encode contextual information and how these representations are affected in SZ. Here we recorded mPFC neurons in a validated SZ-mouse model (NMDA receptors ablated in corticolimbic GABAergic interneurons, KO) and control mice during exploratory tasks with varying emotional and cognitive loads: a social-object discrimination task (SO) and Y-maze spontaneous alternation test (YM). In the SO task, nearly half of the recorded neurons exhibited discriminating responses either to the location of the social stimulus, the object or both. Also, in YM we found 26% neurons encoding the center of the maze just before the turning decision point suggesting they are involved in the decision making process. Notably, KO mice maintained response quality of encoding neurons in both tasks, but we detected a significant reduction in the percentage of responding neurons at the population level. These results suggest an underrepresentation and altered recruitment pattern of cortical units during heightened cognitive demands in KO mice. Our findings provide insights into mPFC’s cognitive resource allocation during exploratory behaviors and its relevance to SZ-related cognitive disorders.