Title: Neural Representation of Context and Task Rules in the Auditory Cortex during Flexible Decision-Making

Animals must flexibly interpret sensory stimuli according to context in order to guide adaptive behavior. Although the primary auditory cortex (A1) has traditionally been viewed as a sensory processor specialized for encoding acoustic features, growing evidence suggests that its activity is strongly modulated by behavioral state, task engagement, and internal expectations. However, it remains unclear whether A1 carries explicit representations of task rules when identical sensory stimuli must be interpreted differently across contexts, and whether such representations are necessary for flexible decision-making. To address this question, I will use the Continual Learning Mouse Playground, a high-throughput behavioral platform in which freely moving mice perform context-dependent auditory decisions. Mice will learn two two-alternative forced choice (2AFC) tasks using the same auditory stimuli, while the correct rule depends on spatial context. Stimuli are drawn from a parametrically structured auditory space, enabling quantitative analysis of feature weighting, decision boundaries, and generalization. This design isolates the computation of assigning context-dependent behavioral meaning to sensory input rather than simple stimulus-response learning. My central hypothesis is that A1 supports flexible behavior by representing sensory information in a context-dependent format that links stimulus identity, task rule, and expected outcome. To test this hypothesis, Aim 1 will determine whether A1 is causally required for expert context-dependent decisions using temporally specific optogenetic silencing during distinct trial epochs. Aim 2 will use longitudinal two-photon calcium imaging in freely behaving mice to define how A1 neural populations encode sensory features, contextual variables, reward expectation, and preparatory task states during flexible behavior.

This work will establish whether a primary sensory cortex participates directly in context-dependent computation and cognitive flexibility. More broadly, these studies will provide mechanistic insight into how cortical circuits dynamically integrate sensory and non-sensory information to guide adaptive behavior, with implications for understanding disorders characterized by impaired cognitive flexibility, including schizophrenia, autism spectrum disorder, and ADHD.