thalamic reticular nucleus
Organization of thalamic networks and mechanisms of dysfunction in schizophrenia and autism
Thalamic networks, at the core of thalamocortical and thalamosubcortical communications, underlie processes of perception, attention, memory, emotions, and the sleep-wake cycle, and are disrupted in mental disorders, including schizophrenia and autism. However, the underlying mechanisms of pathology are unknown. I will present novel evidence on key organizational principles, structural, and molecular features of thalamocortical networks, as well as critical thalamic pathway interactions that are likely affected in disorders. This data can facilitate modeling typical and abnormal brain function and can provide the foundation to understand heterogeneous disruption of these networks in sleep disorders, attention deficits, and cognitive and affective impairments in schizophrenia and autism, with important implications for the design of targeted therapeutic interventions
Thalamic reticular nucleus dysfunction in neurodevelopmental disorders
The thalamic reticular nucleus (TRN), the major source of thalamic inhibition, is known to regulate thalamocortical interactions critical for sensory processing, attention and cognition. TRN dysfunction has been linked to sensory abnormality, attention deficit and sleep disturbance across multiple neurodevelopmental disorders. Currently, little is known about the organizational principles underlying its divergent functions. In this talk, I will start with an example of how dysfunction of TRN contributes to attention deficit and sleep disruption using a mouse model of Ptchd1 mutation, which in humans cause neurodevelopmental disorder with ASD. Building on these findings, we further performed an integrative single-cell analysis linking molecular and electrophysiological features of the TRN to connectivity and systems-level function. We identified two subnetworks of the TRN with segregated anatomical structure, distinct electrophysiological properties, differential connections to the functionally distinct first-order and higher-order thalamic nuclei, and differential role in regulating sleep. These studies provide a comprehensive atlas for TRN neurons at the single-cell resolution and a foundation for studying diverse functions and dysfunctions of the TRN. Finally, I will describe the newly developed minimally invasive optogenetic tool for probing circuit function and dysfunction.