A corticocortical circuit directly links retrosplenial cortex to M2 in the mouse

Retrosplenial cortex (RSC) is a dorsomedial parietal area involved in a range of cognitive functions, including episodic memory, navigation, and spatial memory. Anatomically, the RSC receives inputs from dorsal hippocampal networks and in turn projects to medial neocortical areas. A particularly prominent projection extends rostrally to the posterior secondary motor cortex (M2), suggesting a functional corticocortical link from the RSC to M2 and thus a bridge between hippocampal and neocortical networks involved in mnemonic and sensorimotor aspects of navigation. We investigated the cellular connectivity in this RSC→M2 projection in the mouse using optogenetic photostimulation, retrograde labeling, and electrophysiology. Axons from RSC formed monosynaptic excitatory connections ontoM2pyramidal neurons across layers and projection classes, including corticocortical/intratelencephalic neurons (reciprocally and callosally projecting) in layers 2– 6, pyramidal tract neurons (corticocollicular, corticopontine) in layer 5B, and, to a lesser extent, corticothalamic neurons in layer 6. In addition to these direct connections, disynaptic connections were made via posterior parietal cortex (RSC→PPC→M2) and anteromedial thalamus (RSC→AM→M2). In the reverse direction, axons from M2 monosynaptically excited M2-projecting corticocortical neurons in the RSC, especially in the superficial layers of the dysgranular region. These findings establish an excitatory RSC→M2 corticocortical circuit that engages diverse types of excitatory projection neurons in the downstream area, suggesting a basis for direct communication from dorsal hippocampal networks involved in spatial memory and navigation to neocortical networks involved in diverse aspects of sensorimotor integration and motor control.