Wu Tsai Neurosciences Institute Seminar Series Presents
Thalamic reticular nucleus dysfunction in neurodevelopmental disorders
Guoping Feng, PhD
Brain and Cognitive Sciences; Director, Model Systems and Neurobiology, Stanley Center for Psychiatric ResearchMcGovern Institute, Massachusetts Institute of Technology - MIT
Host: Sergiu Pasca
The Thalamic reticular nucleus (TRN) provides major inhibitory inputs to the thalamus and plays important roles in sensory gating, attention selection and sleep rhythms. Many of the risk genes for ASD, schizophrenia and ADHD are highly expressed in the TRN, raising the possibility that TRN may be a circuit converging point for some of the overlapping behavioral abnormalities in these disorders. Using TRN-specific genetic deletions in mice, we demonstrate the critical roles of TRN dysfunction in attention deficit, hyperactivity and sleep disruption, commonly observed in neurodevelopmental disorders including ASD. To dissect how TRN may differentially regulate distinct aspects of thalamo-cortical function, we applied multi-scale single cell analysis including single cell RNA-Seq, multiplex RNA FISH, electrophysiological recordings and molecular tracing to map TRN subnetworks. We identified two major TRN neuronal subtypes that have distinct electrophysiological properties, differential topographic connectivity related to different thalamic sensory modalities, i.e. first order and high order thalamic nuclei. Through such non-overlapping anatomical pathways mediated by its subpopulations, TRN might differentially tune incoming sensory information through thalamo-cortical circuits. Importantly, we identified genes selectively expressed by each of the TRN subtypes of neurons, paving the way for testing molecular targets that could potentially regulate different TRN functions based on their thalamic connectivity.