Layer 5 Martinotti and pyramidal neurons encode spatial information in the primary motor cortex

Abstract Mammals rely on external sensory cues and internal bodily signals to create a precise spatial awareness. The motor cortex is essential for this process, integrating proprioceptive and spatial information. Here, we investigate how layer 5 martinotti (M α 2) interneurons and pyramidal cells contribute to spatial processing in primary motor cortex (M1). Using miniscopes in freely moving mice expressing CaMKIIa-GCaMP8f or DIO-GCaMP8f in Chrna2-Cre+ mice, we recorded activity from both cell types. We found that both M α 2 and pyramidal cells are tuned to place, head direction, and grid fields, with distinct characteristics. Notably, both cell types exhibit an overrepresentation of co-tuned place- and head-direction responses compared to chance. Moverover, pyramidal head direction-tuned cells show sharper tuning than M α 2 head direction-tuned cells. Further, place-tuned Mα2 cells are more active, whereas pyramidal place-tuned cells showed reduced activity compared to non-place-tuned ones. Additionally, both cell types exhibit lower activity in head-direction-tuned compared to non-head direction-tuned cells. These findings suggest that distinct neural coding strategies are employed by different cell types within the M1 for processing spatial information, highlighting the complex neural mechanisms underlying spatial cognition.