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bioRxiv · 10.64898/2026.10.14.759116

Thalamocortical, not Intracortical, Inputs Set the Wakeful Activity Levels of Cortical Visual Inhibition

Sibille, J.·Teh, K. L.·Pysall, J. A.·Kremkow, J.
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Abstract

Cortical neurons integrate from a wide range of synaptic inputs, locally within the cortex and distally from multiple brain sources, which altogether support the generation and transmission of spikes. Yet, the relative influence on local cortical processing between thalamocortical and intracortical inputs still remains poorly understood. Here, we used tangential insertion of high-density silicon probes to capture thalamocortical next to intracortical functional connectivity, thereby unraveling their relative contribution to local cortical dynamics. By comparing wakefulness versus light anesthesia, we revealed a marked wakeful increase of firing in specifically thalamocortical axons and putative cortical inhibitory neurons; an increase which is very homogeneous in both populations, and comparatively absent in neighboring cortical excitatory neurons. Such specific comodulation is attributable to the known preferential connectivity of thalamocortical axons toward putative cortical inhibitory neurons, which we quantified to follow a 90/10% preference. In addition, we uncovered that wakeful increases of activity levels are symmetric in thalamocortical synapses and asymmetric in intracortical synapses. Indeed, within intracortical synapses, the wakeful increases of firing mostly happen in receiving neurons, leaving pre-synaptic upstream neurons barely impacted by wakefulness. In the meantime, thalamocortical receiving excitatory neurons exhibit a marked wakeful increase of firing, unlike the rest of the excitatory cortical population. Using mathematical modelling simulating spike transmission in thalamocortical and intracortical networks, we showed that only outnumbering thalamocortical-to-intracortical inputs could mimic the observed homogeneous wakeful increases of firing in thalamocortical and cortical inhibitory neurons. Altogether, our results identify thalamocortical synaptic inputs as a key controller of the wakeful level of firing of inhibitory neurons at the first relay of visual cortical processing.

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Sibille, J., Teh, K. L., Pysall, J. A., Kremkow, J.. 2026-10-16. Thalamocortical, not Intracortical, Inputs Set the Wakeful Activity Levels of Cortical Visual Inhibition. https://doi.org/10.64898/2026.10.14.759116

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