Dissection of inter-area interactions of motor circuits

Behaviors are known to arise from numerous neurons communicating with each other within and across brain areas. Less is known about the precise nature of long-range neural interactions that give rise to global activity patterns in the brain during behavior. Recent advances in experimental and computational techniques present the opportunity to examine such interactions at an unprecedented level of detail. In this project, we will investigate cell-type-specific interactions among three brain areas involved in motor control. This will be done in a close collaboration between computational and experimental groups at the University of California, San Diego.

Motor regions of the cerebral cortex, striatum and thalamus form a central circuit involved in initiating and executing movements, with the cortex and thalamus providing the main excitatory inputs to the striatum. We will record the activity of these three circuit components during several motor behaviors. Furthermore, we will use monosynaptic rabies virus to identify and monitor corticostriatal and thalamostriatal neurons that specifically project onto two distinct subpopulations of the striatum, direct- and indirect-pathway medium spiny neurons (MSNs), the principal neurons of the striatum. By selectively recording the activity of these specific and interconnected functional elements in behaving mice, we aim to dissect the dynamic interactions among motor regions during various behavioral contexts.

Understanding the relationships between population activity from multiple brain regions requires new approaches to data analysis. To study information flow within this motor circuit, we will develop new multimodal dimensionality-reduction approaches and extract shared features and temporal relationships of activity dynamics between striatal cells and their upstream inputs. These analyses will reveal cell-type-specific activity patterns in the striatum and how they are shaped by distinct upstream inputs. We will complement this analytical approach by examining the effects of optogenetic manipulations of distinct inputs on the striatal activity at specific time points of the motor tasks. The proposed experiments will reveal pathway and cell-type specificity of communications among motor regions of the brain in movement execution.