Motor feedback control of layer six circuits

This study investigates how motor cortex signals engage distinct layer 6 corticothalamic (L6 CT) circuits in somatosensory cortex to influence thalamic processing. The study focuses on vM1 (vibrissal primary motor cortex) inputs to vS1 (vibrissal primary somatosensory cortex) and examines whether and how these motor-related inputs selectively recruit CT neurons that differ in their intrathalamic projection patterns and laminar position. Using mice of either sex, the team combined in vitro electrophysiology, optogenetic activation of vM1 afferents, retrograde labeling to identify CT neurons by thalamic projection target, confocal imaging, histological methods, and targeted analyses of intrinsic and synaptic properties.

The work begins from the premise that L6 CT neurons are anatomically positioned to modulate thalamic processing, given that descending L6 CT axons outnumber ascending thalamocortical axons and contribute a substantial fraction of synapses onto thalamic relay neurons. Despite this central role, CT neurons are diverse, many are silent or unresponsive to sensory stimuli in vivo, and it remains unclear which afferent pathways control CT activity. vM1 is a prominent non-sensory input to vS1, terminating densely in infragranular layers and correlating with vibrissa movement. Thus, vM1 is a candidate pathway to communicate motor plans to vS1 and to gate or modulate thalamic throughput via CT circuits during active touch.

The authors report that vM1 inputs are highly selective: they evoke stronger postsynaptic responses in CT neurons that project to both the ventral posterior medial nucleus (VPm) and the posterior medial nucleus (POm) — termed Dual CT neurons — located in lower L6a, compared to CT neurons that project only to VPm and reside in upper L6a. Targeted analyses revealed that this greater responsiveness of Dual CT neurons arises from distinctive intrinsic membrane properties and specific synaptic mechanisms at vM1-to-CT synapses. These results indicate that vS1 contains at least two discrete L6 CT subcircuits distinguished by thalamic projection pattern, laminar position, intrinsic physiology, and functional connectivity with vM1.

By demonstrating that a distinct subclass of L6 CT neurons is preferentially engaged by motor cortex input, the study provides mechanistic insight into how motor-related contextual signals might selectively modulate tactile-related sensory processing in the somatosensory thalamus during active vibrissa movements. The findings advance understanding of the cellular and synaptic bases for corticothalamic feedback control and suggest a model in which subcircuit-specific recruitment of CT neurons by motor cortex enables specialized contextual modulation of thalamic information flow. This work thus refines the view of corticothalamic feedback as a heterogeneous, subdivided system capable of targeted modulation tied to behaviorally relevant motor signals.