CRCNS: Dynamics of thalamocortical networks during sensory discrimination

Thalamocortical networks are critical for basic neural sensory processing and for foundational cognitive functions such as attention, perception, and working memory. Dysfunction of these networks is thought to affect symptomology of several neurological disorders and some psychiatric disorders; however, the dynamics of thalamocortical networks during everyday tasks are poorly understood even in healthy cognitive function. The thalamus is a complex aggregation of nuclei with distinct roles and connection patterns. Fundamental questions remain regarding how these many distinct nuclei interact with the various sensory, motor and association areas in cortex. In particular, the roles of higher-order thalamic nuclei, each of which projects diffusely across several cortical regions, and the role of the thalamic reticular nucleus, which inhibits most other thalamic nuclei, remain poorly understood. In order to clarify the dynamic interactions within thalamocortical networks, this study will measure activity in all dorsal regions of cortex and in many thalamic nuclei during a variety of sensory discrimination tasks, similar to those tasks commonly used for studies of cognitive function in health and disease. We will simulate impairment of several distinct thalamic regions through optogenetic inhibition to elucidate their roles in comparisons. Next, we will investigate how these dynamic interactions between the thalamic nuclei and cortical regions develop as animals begin to learn these tasks and as they acquire skilled performance. A key aspect of our design is that we will carefully monitor spontaneous motions and our analyses will control for activity in the thalamic nuclei related to these movements, which are often correlated with cognitive tasks, and would otherwise confound the analyses. This project will elucidate the roles of the different higher-order thalamic nuclei and of cortical feedback to these nuclei in gating cognitive processes across several sensory modalities. We expect these findings to yield many insights about thalamocortical network function during sensory processing, leading to greater understanding of cognitive function in the animal models used to study neurological and psychiatric disorders.