“Segregated auditory cortico-striatal pathways undergo distinct learning-related plasticity”
Tanya Sippy, MD, PhD
Assistant Professor
Departments of Psychiatry and Neuroscience
Institute of Translational Neuroscience
New York University School of Medicine
Abstract: The ability to translate sensory experiences into appropriate actions is crucial for survival, and its disruption is a hallmark of several neuropsychiatric disorders, including depression, autism, and schizophrenia. While the striatum has long been recognized for its role in initiating and selecting motor commands, emerging evidence underscores its involvement in sensory processing. Notably, the posterior dorsal striatum (pDS) receives topographically organized input from auditory, visual, and somatosensory cortical areas, implicating it in sensory-guided behavior. As our investigation progressed, we discovered that each sensory modality projects to at least two distinct “hotspots” within the striatum. This led us to ask: How do topographically distinct regions of the striatum, which receive input from the same sensory modality, differ in function? To address this, we conducted anatomical and functional studies in mice, focusing on two striatal regions that receive dense auditory input: the posterior dorsolateral striatum (pDS) and the dorsomedial striatum (dMS). Specifically, we (1) examined the specificity of auditory cortical projections to these sub-regions, (2) assessed their distinct contributions to behavior, and (3) measured the activity of downstream striatal neurons during auditory sensorimotor learning. Our findings revealed that largely non-overlapping populations of auditory cortex neurons project to the pDS and dMS, with each pathway displaying distinct learning-dependent response profiles. Moreover, neurons in the pDS and dMS exhibited strikingly different responses to auditory cues, with pDS neurons uniquely showing disengagement during task performance. Functional experiments further confirmed that pDS neurons are integral to auditory-driven sensorimotor learning. These results expand the traditional view of the striatum as a primarily motor structure and provide a framework for investigating how sensory-guided actions are shaped by distinct cortico-striatal circuits. Current work is focused on elucidating the functional contributions of dMS-projecting neurons and exploring the behavioral significance of the distinct response dynamics observed in these two auditory regions of the striatum.
Host: Jose Figueroa, Berke Lab