Complexity of D1R and D2R Striatal Projection Neurons in Tail Striatum – CODETAILS

Efficient sensory processing is vital for survival, and disruptions in this process often lead to over- or under-responsiveness, commonly seen in neurodevelopmental disorders like autism and ADHD.Iit is crucial to identify and understand the neural circuits and cellular mechanisms involved in sensory processing to address deficits associated with aberrant sensory processing. The tail striatum (TS, the extreme caudal part of the striatum) is a crucial hub for sensory processing. Striatal projection neurons (SPNs) in the TS filter and select relevant sensory information to produce precise behavioral responses. Imbalances in SPN activity have been linked to heightened or diminished responsiveness to sensory stimuli. This disparity can lead to stereotyped and perseverative behaviors, all common symptoms of sensory processing disorders. The TS exhibits a unique arrangement of D1R- and D2R/A2aR-SPNs and PV interneurons, indicating a non-random distribution, apart from the anterior dorsal striatum. Yet, the molecular and functional attributes of SPNs within these newly identified TS subdomains remain largely unexplored. To comprehend TS functions, a spatially resolved map of gene expression, connectivity, and neuronal characteristics in D1R- and D2R/A2aR-SPNs and PV interneurons across TS domains must be constructed, while also uncovering their roles in influencing behavior.
Our general objective is to develop a comprehensive understanding of the molecular and functional properties of SPNs’ subtypes within distinct TS subdomains to unravel their non-random distribution and behavior functions. This project will encompass four specific objectives: 1/ Decode the molecular diversity and connectivity of D1R- and D2R/A2aR-SPNs and PV interneurons within TS subdomains. 2/ Unravel the synaptic and morphological characteristics of these SPNs in TS subdomains. 3/ Explore the involvement of SPNs and PV interneurons in TS subdomains across various behavioral domains. 4/ Examine the effects of prolonged sensory disturbances on SPN functions within TS subdomains.