Organization of cortical and thalamic input to inhibitory neurons in mouse motor cortex

ABSTRACT Intracortical inhibition in motor cortex (M1) regulates movement and motor learning. If inhibitory cell types and cortical laminae targeted by cortical and thalamic afferents differ, then these afferents play different roles in regulating M1 output. We quantified input to two classes of M1 interneurons, parvalbumin+ (PV) fast-spiking cells and somatostatin+ (SOM) low-threshold-spiking cells, using monosynaptic rabies tracing. We then compared anatomical connectivity and functional connectivity based on synaptic strength from sensory cortex and thalamus. Functionally, each input innervated M1 interneurons with a unique laminar profile. Different interneuron types were excited in a distinct, complementary manner, suggesting feedforward inhibition proceeds selectively via distinct circuits. Specifically, somatosensory cortex (S1) inputs primarily targeted PV+ neurons in upper layers (L2/3) but SOM+ neurons in middle layers (L5). Somatosensory thalamus (PO) inputs targeted PV+ neurons in middle layers (L5). In contrast to sensory cortical areas, thalamic input to SOM+ neurons was equivalent to PV+ neurons. Thus, long-range excitatory inputs target inhibitory neurons in an area and cell type-specific manner which contrasts with input to neighboring pyramidal cells. In contrast to feedforward inhibition providing generic inhibitory tone in cortex, circuits are selectively organized to recruit inhibition matched to incoming excitatory circuits.