Distinct functional roles and connectivity rules for lower- and higher-order intracortical and pulvinar thalamocortical pathways in mouse visual cortex

Functional specialization of cortical areas is a fundamental feature of brain organization and is critical for perception and behavior. Such an organization must depend on specialized connectivity between areas, yet the underlying wiring rules remain unclear. We characterized intracortical and thalamocortical pathways in the mouse visual cortex using neural tracing and functional imaging. We uncovered multiple structural-functional connectivity rules underlying the functional specialization of higher visual cortical areas (HVAs). Individual higher visual areas integrate specific cortical and thalamic inputs with distinct functional biases. Higher order Layer 2/3 and thalamocortical pathways show higher target specificity than feedforward intracortical pathways and might impart specific functional preferences to the recipient HVAs. In contrast, higher order Layer 5 pathways lacking specificity may contribute to the tuning diversity in the recipient HVAs. Altogether, this study reveals fundamental organization rules of long-range interareal connectivity that underlie the parallel modular organization of the visual cortex. HIGHLIGHTSO_LIHVAs AL, PM and A receive diverse and specific inputs from V1, HVA and LP pathways C_LIO_LIDensity of intracortical inputs correlates with similarity of tuning between visual areas C_LIO_LITuning of HVA inputs correlates with HVAs preferences and functional heterogeneity C_LIO_LIHVA output pathways differ in tuning homogeneity and target specificity C_LI