Plasticity in primary motor cortex (M1) circuitry is essential for motor learning and skilled performance. Maladaptive plasticity contributes to movement disorders such as dystonia. This proposal focuses on the role of inhibition in adaptive plasticity. How specific types of inhibitory neurons in M1 are recruited by sensorimotor inputs is unknown.
Aim 1 explores monosynaptic excitation to three different interneuron types: parvalbumin (PV), somatostatin (SOM) and vasoactive intestinal peptide (VIP) expressing neurons. We will quantify the strength of corticocortical and thalamocortical inputs to each of these three cell types. We will use whole-cell recording of transgenically labeled neurons in acute brainslices. We will use optogenetic approaches to specifically stimulate corticocortical and thalamocortical inputs and quantify synaptic strength. Our preliminary data show that thalamus and cortex excite PV+ interneurons in complementary subsets of interneurons in different cortical layers. Since synaptic plasticity follows different rules between these two pathways, and inhibition regulates cortical plasticity, this different may help explain why plasticity in these circuits is different.
Aim 2 studies the disynaptic inhibition provided by cortical and thalamic inputs. We will determine if inhibition is recruited in pathway-specific circuits, or as a general blanket for silencing all of cortex. We hypothesize that different M1 inputs recruit different sources of inhibition, allowing cortical circuits to specifically tune the gain of inhibition to the incoming input, instead of a generically downregulating all local circuitry.
Aim 3 will identify sites of plasticity at interneuron connections by developing an M1-dependent skilled reaching task. We will then record inhibition to neurons active and inactive during the task to compare amplitude of inhibition from PV+ or SOM+ interneurons. Collectively, these Aims will determine the connections by which inhibition is recruited by distinct inputs to motor cortex, identifying the specific cell types targeted and how these circuits contribute to plasticity during motor learning. Because disruption of M1 circuitry is implicated in movement disorders, knowledge about the circuitry of M1 may contribute to targeted approaches to treat M1 dysfunction.
Motor cortex regulates movement control and skill learning, and pathology in motor cortex results in paralysis, dystonia, and other movement disorders. Cortical inhibition is critical for normal motor cortex function and plasticity. The proposed studies will provide insight into the inputs and outputs of specific inhibitory circuit components of motor cortex, and how these connections change in skill learning. This is consistent with the NINDS mission to ?seek fundamental knowledge about the brain? and use it to ?reduce the burden of neurological disease.?