A Gradient of Hippocampal Inputs to the Medial Mesocortex

Abstract

AbstractMemory-guided decisions depend on complex, finely tuned interactions between hippocampus and medial mesocortical regions anterior cingulate and retrosplenial cortices. The functional circuitry underlying these interactions is unclear. Using viral anatomical tracing,in vitroandin vivoelectrophysiology, and optogenetics, we show that such circuitry is characterized by a functional-anatomical gradient. While CG receives excitatory projections from dorsal-intermediate CA1 originated exclusively instratum pyramidale, retrosplenial cortex also receives inputs originating instratum radiatumandlacunosum-moleculare, including GAD+ neurons providing long-range GABAergic projections. Such hippocampal projections establishbona fidesynapses throughout cortical layers, with retrosplenial cortex densely targeted on its layer 3, around which it receives a combination of inhibitory and excitatory synapses. This gradient is reflected in the pattern of spontaneous oscillatory synchronicity found in the awake-behaving animal, compatible with the known functional similarity of hippocampus with retrosplenial cortex, which contrasts with the encoding of actions and “task-space” by cingulate cortex.HighlightsBoth MMC regions CG and RSC receive monosynaptic connections from the dorsal-intermediate CA1CG receives layer-sparse excitatory projections exclusively originated fromstratum piramidalewhereas RSC is targeted densely in superficial layers by a mixed excitatory and inhibitory input originating from all CA1strataCA1 monosynaptic projections correspond to active synapses onto distinct layers of the two MMC regionsDiverse synchrony between MMC and HIPP recordedin vivois consistent with the rostro-caudal diversity of direct HIPP-MMC connections