PATHWAY-SPECIFIC MODULATION OF MEMBRANE POTENTIAL DYNAMICS IN LAYER 2/3 PYRAMIDAL NEURONS OF THE MOUSE SOMATOSENSORY CORTEX <EM>IN VIVO</EM>

Layer 2/3 (L2/3) pyramidal neurons (PNs) in primary somatosensory cortex (S1) integrate long-range inputs that shape sensory processing, yet the temporal impact of distinct pathways remains unclear. We examined how axons from the ventral posterior medial thalamic nucleus (VPM), posterior medial thalamic nucleus (POm), primary motor cortex (M1), and contralateral S1 (contraS1) modulate whisker-evoked responses. Using optogenetic activation of these pathways combined with whole-cell recordings from L2/3 PNs in anesthetized mice, we analyzed evoked subthreshold depolarizations separated into early (0–0.1 s), intermediate (0.1–0.2 s), and late (0.2–0.5 s) phases. Photostimulation of VPM and POm axons (100 ms) produced robust, multi-millivolt depolarizations spanning all three phases and lasting up to ~1 s. M1 activation elicited similar sustained responses but with a weaker intermediate phase. In contrast, contraS1 activation generated only brief, fast depolarizations that did not persist into intermediate or late phases. When paired with whisker stimulation, VPM and POm activation increased both the magnitude and probability of early and late whisker-evoked depolarizations. M1 activation selectively enhanced late-phase responses, whereas contraS1 activation suppressed them. These results indicate that thalamocortical pathways broadly facilitate sensory responses in L2/3 PNs, while corticocortical inputs exert pathway-specific modulation that may engage inhibitory mechanisms to sculpt response dynamics. Ongoing work aims to identify the cellular mechanisms and functional consequences of this differential modulation.