Sensory Plasticity in the Auditory Striatum as an Impetus for Action Control - Diversity Supplement

Project Summary Despite its importance in health and disease, we know remarkably little about how we assign meaning to and use sensory stimuli to guide behavior. The striatum is thought to be particularly important for the formation of sensorimotor associations during reinforcement learning due to the dopaminergic inputs it receives, as well as a diverse array of cortical and subcortical inputs. The parent R01 focuses on understanding how the output neurons in a particular region of the striatum, the auditory striatum (AudStr), encode auditory stimuli before and after learning. While the AudStr is a major target of auditory projections from primary auditory regions, the dorsomedial striatum (DMS) is another hotspot for these projections. The AudStr and the DMS are thought to have different functional roles, with the AudStr important for the execution of sensorimotor associations and the DMS important for the learning of these associations. However, it is unclear how the auditory projections to these regions and the neurons that are targeted by these inputs are activated by auditory stimuli before and after learning. Understanding this would contribute to our understanding of how sensory projections to the striatum contribute to forming cue-response associations important for the generation of appropriate behavior. In this diversity supplement, we will perform two independent, inter-related aims to address this gap in knowledge. In Aim 1, we will investigate the anatomical and functional properties of auditory cortex (AudCx) neurons that project to the DMS and AudStr. We predict that these neurons will be discreet, mostly non- overlapping populations. We will then measure the activity of AudCx projections into the DMS and AudStr in mice as they learn a task that requires them to associate a 'go' cue with a specified action to receive a reward, and to suppress this action in response to a 'no-go' cue, predicting that these projections will have different time courses in their plasticity profiles. In Aim 2, we will employ longitudinal two-photon (2P) calcium imaging in the DMS, where we will quantify the activity-evoked responses of striatal projection neurons belonging to the direct (dSPNs) and indirect (iSPNs) output pathways of the striatum. We predict that the neurons in the DMS will have distinct evoked responses that are more heavily modulated by reward as compared to the AudStr. Together, this work will lay the foundation for how we can understand the role of sensory inputs to distributed regions of the striatum in sensorimotor learning.