Altered Use of Prior Expectations and Modified Neural Dynamics in a Mouse Model of Autism

Abstract

In dynamic environments, updating beliefs based on past experiences (priors) is essential for optimal decision-making. Prior utilization is often impaired in psychiatric disorders, affecting perception and behavior. We investigate how Neurexin1 (Nrxn1 ) loss-of-function disrupts this process, providing insight into circuit deficits underlying sensorimotor dysfunction. While the synaptic role of Nrxn1 role is well studied, its impact on network dynamics and decision-making behavior remain unclear. Using widefield calcium imaging, we assess cortex-wide activity in mice performing a two-choice task to probe how priors influence visually-guided decisions. This task requires the mouse to combine sensory evidence with the prior probability over the stimulus side. We find Nrxn1 KO mice underutilized priors and were slower to update choices based on feedback. During decision-making, cortex-wide cortical activity is both elevated and increasingly correlated in Nrxn1 KO mice, independent of task period. Moreover, a larger fraction of cortical variance was explained by movement variables, consistent with stronger coupling of cortical activity to motor signals and a bias toward movement-related dynamics. These findings suggest that core computations underlying decision-making, such as integrating past experience with current evidence, depend on intact synaptic mechanisms shaped by genes like Nrxn1.