Brief Visual Deprivation Selectively Remodels Intracortical Inputs onto Layer 6 Corticothalamic Neurons in Primary Auditory Cortex.

Loss of one sensory modality can enhance processing in spared systems. Brief visual deprivation by dark exposure (DE) enhances auditory responses in the primary auditory cortex (A1) of adult mice, increasing firing rates, frequency selectivity, and behavioral performance. This enhancement is accompanied by reduced inhibition of the auditory thalamus (MGBv) and strengthened thalamocortical and intracortical feedforward inputs. While the mechanisms coordinating cross-modal cortical and thalamic plasticity are unknown, Ntsr1+ layer 6 corticothalamic neurons (L6-CTNs) are a promising candidate given their regulation of both cortical and thalamic gain. Here, we examined how 1 week of DE in both male and female adult mice alters intracortical synaptic inputs onto A1 L6-CTNs using laser-scanning photostimulation (LSPS) and whole-cell recordings. We found DE selectively reduced excitatory intracortical connectivity onto L6-CTNs across multiple layers and weakened synaptic strength from infragranular inputs. In contrast, inhibitory inputs were largely preserved. This shift resulted in a layer-specific reduction in excitation-inhibition balance, particularly for inputs from layer 4. Although the spatial extent of inputs was unchanged, DE decreased the within-animal similarity of excitatory input patterns across neurons, indicating a reorganization of circuit structure. Together, these findings identify selective weakening of intracortical excitation onto L6-CTNs as a key feature of cross-modal plasticity. By reducing recruitment of the L6 gain-control circuit, this reconfiguration may bias cortical processing toward enhanced sensory discrimination while preserving sensitivity.Significance Statement Sensory deprivation induces thalamic and cortical plasticity that can enhance processing in spared sensory systems. Layer 6 corticothalamic neurons (L6-CTNs) regulate cortical and thalamic activity, but how deprivation alters their circuitry is unknown. Using laser-scanning photostimulation in adult mouse auditory cortex, we found that brief visual deprivation selectively reduced the area and strength of intracortical excitatory inputs onto L6-CTNs while largely preserving inhibition. This reconfiguration shifted excitation-inhibition balance toward inhibition and reduced within-animal similarity of excitatory input patterns. These findings identify weakening and reduced stereotypy of intracortical excitation onto L6-CTNs as features of cross-modal plasticity, suggesting that remodeling of the L6 feedback circuit may coordinate plasticity across cortical and thalamic components of a spared sensory system.