Subtype-Specific Connectivity of Local Inhibitory Interneurons in the Motor Cortex

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The brain is a network that consists of diverse types of neurons and their connections provide the framework for information flow in the brain. Mapping neuronal connectivity within mammalian brains has been a long-standing and important goal in neuroscience because a clearer understanding of communication between and within brain regions will be key to uncovering the new brain functions such as formation and acquisition of complex movements. Mammals possess a remarkable ability to learn and consistently execute a wide range of movements with high levels of control. The primary motor cortex has been shown to produce voluntary movement and store movement-related memories, allowing new motor patterns to be learned. Considerable research efforts have been aimed at understanding how the motor cortex enables the generation and acquisition of new movements. Although a substantial body of knowledge pertaining to neural network dynamics within the motor cortex during motor skill learning has been explored, the fundamental question of which regions and which neurons the motor cortex communicates with remains elusive. Therefore, understanding the basic anatomical and functional wiring diagram of the motor system, with cell-type specificity, is an essential step in improving our understanding of the cortical mechanisms enabling motor movements and motor learning. Our lab has previously demonstrated that motor learning causes differential remodeling of inhibition along pyramidal neurons that is mediated by distinct populations of local inhibitory interneurons in the motor cortex. Hence, it is intriguing to understand whether different subtypes of inhibitory neurons receive inputs from different brain regions. In this proposal, we will focus on a specific subtype of inhibitory interneurons, the vasoactive intestinal peptide-expressing interneurons (VIP-INs). We will employ the newly developed monosynaptic rabies virus tracing method, combined with the Cre-recombinase strategy, to unbiasedly map brain-wide inputs to VIP-INs in the motor cortex. We will also examine the functional connectivity of these inputs using in vitro and in vivo approaches. Results from this proposal will provide insights to unknown connections that may be important in motor skill learning. The same methodologies can be applied to understand the connectivity of other inhibitory neuron subtypes in the motor cortex to help us to fully dissect the complex wiring diagram of the motor system in the brain.