Thalamic input drives co-timed excitation and inhibition to suppress cortical neuronal variability during movement initiation

Abstract

Cortical activity is inherently dynamic, with ongoing fluctuations introducing variability into sensory-to-motor transformations. During movement initiation, neural variability in the motor cortex is sharply reduced, or "quenched," a general phenomenon thought to ensure reliable population responses across cortical areas. However, the synaptic and circuit-level basis for this reduction in neural variability remains unclear. Here, we show that excitatory and inhibitory neurons in layer 5B of mouse motor cortex are co-activated during movement initiation in a cued forelimb push task. Co-timed excitation and inhibition drive pyramidal neuron membrane potential (Vm) trajectories towards the compound synaptic reversal potential, stabilizing the Vm and reducing trial-by-trial variability. Gain- and loss-of-function experiments demonstrate that thalamocortical input is critical for the coordinated recruitment of both excitation and inhibition and variability quenching at the cellular level, while also driving a cortical network state permissive for the expression of reproducible output dynamics. Our findings uncover a simple yet fundamental feedforward mechanism where thalamic input drives neural variability quenching to ensure reliable, structured population dynamics during movement initiation.