NRSA for John Chen: The Role of Cortical D1R-expressing Neurons in Taste-based Sensorimotor Transformations

PROJECT SUMMARY To survive, animals must use gustatory sensory stimuli to inform and guide reward-oriented actions like licking and chewing. Previous work examining this process, known as sensorimotor integration, has established the anterior lateral motor cortex (ALM) as a model brain region to study sensorimotor processing related to licking. Neural activity within this region reflects sensory information and motor planning of licking, implicating ALM in mediating sensory-based lick decisions. However, it remains unknown if ALM is involved in taste-guided sensorimotor integration – despite licking and taste being invariably connected – and whether this process in- volves dopaminergic circuits. Blockade of D1R signaling within ALM has been found to affect both sensory- evoked responses and motor planning of stimuli-guided licking, suggesting a potential role for ALM neurons expressing D1Rs (D1R+ neurons) in lick-related sensorimotor transformations. However, the contributions of D1R+ neurons in taste-guided sensorimotor integration remains unstudied. This proposal will test the central hypothesis that D1R+ neurons are required during gustatory sensorimotor transformation and exhibit patterns of activity representing gustatory processing and preparation of lick choice. The proposed experiments will rely on a recently established 4-taste, 2-alternative choice (2-AC) task in which mice must sample one out of four tastants (i.e., two sweets: sucrose, maltose and two bitters: quinine and sucrose octaacetate) from a central spout and associate pairs with opposite perceptual qualities with specific actions (i.e., sucrose or quinine ? lick left vs maltose and sucrose octaacetate ? lick right) after a delay period. To study the role of D1R+ neurons during this behavior, I will utilize a combination of cutting-edge techniques that include cell-type specific optoge- netic manipulation and 2-photon calcium imaging. To my knowledge, these will be some of the first experiments examining the link between gustatory sensorimotor processing and neurons expressing D1Rs.