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

Abstract

ABSTRACTUnderstanding how feedforward inhibition regulates movement requires knowing how cortical and thalamic projections connect to inhibitory interneurons in primary motor cortex (M1). We quantified excitatory synaptic input from sensory cortex and thalamus onto two main classes of M1 inhibitory interneurons across all cortical layers: parvalbumin (PV) expressing fast-spiking cells and somatostatin (SOM) expressing low-threshold-spiking cells. Each projection innervated M1 interneurons with a unique laminar profile. While pyramidal neurons were excited by these cortical and thalamic inputs in the same layers, different interneuron types were excited in a distinct, complementary manner, suggesting feedforward inhibition from different inputs 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 primarily targeted PV+ neurons in middle layers (L5). Our results show that long-range excitatory inputs target inhibitory neurons in a 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.