Layer-Specific Connectivity and Functional Interference of Chrna2+ Layer 5 Martinotti Cells in the Primary Motor Cortex

The cortical somatostatin interneuron population includes several diverse cell types, among them the Martinotti cells. Layer-specific differences in connectivity and function between different subtypes of Martinotti cells are becoming apparent, which require contemporary studies to investigate cortical interneurons in a layer and subtype-specific manner. In this study, we investigate the connectivity of a subtype of Chrna2+ layer 5 Martinotti cells in the primary motor cortex, using a monosynaptic retrograde rabies viral tracer. We found direct input from pyramidal cells and local parvalbumin interneurons. In addition, we found long-range direct inputs from the motor thalamus, substantia innominata of the basal forebrain, and globus pallidus. Based on the observed input pattern, we tested and found an increased number of falls in the hanging wire test upon temporary overexcitation of Chrna2+ layer 5 Martinotti cells, suggesting that Chrna2+ Martinotti cells in the motor cortex can interfere with sensorimotor integration. In summary, our study provides novel insights into the connectivity and functional role of Mα2 cells in the M1 forelimb area, highlighting their unique integration of local and long-range inputs critical for sensorimotor processing, which lay the groundwork for further exploration of their role in cortical plasticity and motor learning.