INTERHEMISPHERIC BINDING OF MONOCULAR VISUAL CORTICES VIA LAYER 6

Cortical layer 6 (L6) callosal projection neurons (CPNs) are a major source for interhemispheric communication which is believed to mediate tactile integration, sound localization, and visual novelty discrimination. Using viral tracing we demonstrate that the monocular regions of the mouse primary visual cortex (VISp) are interconnected primarily through a subset of excitatory L6 cortico-cortical neurons. Functional characterization using in vitro optogenetics revealed that this contralateral L6 input activates all major L6 excitatory cell types irrespective of whether the target neuron was itself a CPN. Additionally, both parvalbumin and somatostatin-positive interneurons were recruited by CPN input to mediate feedforward inhibition.

In vivo, optogenetic stimulation of the L6 CPN input was found to evoke responses throughout the entire contralateral monocular VISp column. Visual stimulation experiments revealed that ipsilateral eye activation evokes an excitatory early response (R1) and either an exclusive excitatory (R2) or inhibitory late response (R3). Notably, silencing L6 CPN input during ipsilateral eye stimulation selectively abolished the R2 responses without impacting R1 or R3. While thalamic feed-forward early responses to contralateral eye stimulation remained unaffected by L6 callosal input silencing, later phase excitation was reduced and appeared delayed relative to the ipsilateral R2 cortical response. We propose that this major inter-hemispheric pathway functionally binds the two monocular cortices, facilitating a temporally sequenced binocular computation that may be required for higher-order processing.