INVESTIGATING THE ROLE OF LONG-RANGE CORTICOCORTICAL AND THALAMOCORTICAL PROJECTIONS IN SENSORY PERCEPTION

Mice explore the world with their whiskers, whose tactile signals reach whisker primary somatosensory cortex (wS1) via the thalamus. Activity in wS1 is primarily driven by afferents from the ventral posteromedial thalamus (VPM) but is also shaped by long-range glutamatergic inputs from contralateral S1 (cS1) and the higher-order posteromedial thalamus (POm). How these pathways influence perceptual decisions remains unclear. Using slice electrophysiology, neurogliaform cells (NGCs) were identified as synaptic targets of cS1 projections and thus as potential key cellular mediators of interhemispheric inhibition. We tested whether this interhemispheric inhibitory circuit mediates whisker-based sensorimotor behaviour. Head-fixed mice were trained to lick for a reward upon passive whisker deflection and were tested for their ability to detect deflections of varying amplitudes while optogenetically interfering with neuronal activity in wS1. Direct population-wide inhibition of wS1 shifted the psychometric function and increased detection threshold, confirming that the amplitude detection task depends on wS1. Ipsilateral whisker stimulation, which activates interhemispheric cS1 projections to wS1, impaired perception relative to interleaved controls, as did selective activation of NGCs. In a similar set of experiments, either driving POm with rhythmic whisker stimulation or inhibiting POm chemogenetically did not measurably shift psychometric functions. Together, these data identify an NGC-mediated transcallosal inhibitory gate for whisker sensory perception, while POm manipulations under these conditions have limited behavioural impact. Ongoing two-photon imaging of pyramidal neurons in layers 2/3 and 5 (L2/3, L5) and layer 1 dendrites will link pathway-specific modulation to cortical neuronal dynamics during perception and learning.