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.
Ammer, J. J., Dacre, J., Schiemann, J., Moberg, S., Rochefort, N., Hennig, M., Duguid, I.
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