Local inhibitory dynamics underpin temporal integration and functional segregation between barrels and septa in the mouse barrel cortex.

Abstract

Mice, like humans, enhance tactile perception through repeated sampling of spatially segregated sensory inputs. In the whisker system, individual whisker identity is preserved along the whisker-brainstem-thalamus-cortex pathway, culminating in distinct cortical domains: barrels and septa. Using simultaneous in vivo recordings from barrel and septal domains, we identify a progressive divergence in spiking activity during repeated single- and multi-whisker stimulation. While the multi- to single-whisker response ratio remains stable in barrels, it increases progressively in septa, suggesting recruitment of local inhibitory circuits. Genetic fate mapping and tissue clearing revealed distinct laminar and regional distributions of SST+ and VIP+ interneurons in barrel and septal domains. Calcium imaging showed that both interneuron types respond to whisker stimulation, but SST+ interneurons were preferentially recruited during repeated multi-whisker stimulation. Deletion of <i>Elfn1</i>, a regulator of excitatory synaptic dynamics onto SST+ interneurons, abolished the progressive increase in septal multi- to single-whisker response ratios. Temporal decoding analyses further demonstrated a loss of barrel-septa functional segregation in Elfn1 knockout mice. Finally, viral tracing combined with whole-brain clearing revealed distinct projection patterns from barrels and septa to secondary somatosensory (S2) and motor (M1) cortices. Together, these findings support a model in which <i>Elfn1</i>-dependent recruitment of SST+ interneurons contributes to preferential multi-whisker integration and functional specialization within the mouse somatosensory cortex.