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bioRxiv · 10.1101/427179

Long-range inhibitory intersection of a retrosplenial thalamocortical circuit by apical tuft-targeting CA1 neurons

Yamawaki, N.·Li, X.·Lambot, L.·Ren, L. Y.·Radulovic, J.·Shepherd, G. M.
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Abstract

Dorsal hippocampus, retrosplenial cortex (RSC), and anterior thalamic nuclei (ATN) interact to mediate diverse cognitive functions, but the cellular basis for these interactions is unclear. We hypothesized a long-range circuit converging in layer 1 (L1) of RSC, based on the pathway anatomy of GABAergic CA1 retrosplenial-projecting (CA1-RP) neurons and thalamo-restrosplenial projections from ATN. We find that CA1[->]RSC projections stem from GABAergic neurons with a distinct morphology, electrophysiology, and molecular profile, likely corresponding to recently described Ntng1-expressing hippocampal interneurons. CA1-RP neurons monosynaptically inhibit L5 pyramidal neurons, principal outputs of RSC, via potent GABAergic synapses onto apical tuft dendrites in L1. These inhibitory inputs align precisely with L1-targeting thalamocortical excitatory inputs from ATN, particularly the anteroventral nucleus, forming a convergent circuit whereby CA1 inhibition can intercept ATN excitation to co-regulate RSC activity. Excitatory axons from subiculum, in contrast, innervate proximal dendrites in deeper layers. Short-term synaptic plasticity differs at each connection. Chemogenetically abrogating inhibitory CA1[->]RSC or excitatory ATN[->]RSC connections oppositely affects the encoding of contextual fear memory. Collectively, our findings identify multiple cellular mechanisms underlying hippocampo-thalamo-retrosplenial interactions, establishing CA1 RSC-projecting neurons as a distinct class with long-range axons that target apical tuft dendrites, and delineating an unusual cortical circuit in the RSC specialized for integrating long-range inhibition and thalamocortical excitation.

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Yamawaki, N., Li, X., Lambot, L., Ren, L. Y., Radulovic, J., Shepherd, G. M.. 2018-09-25. Long-range inhibitory intersection of a retrosplenial thalamocortical circuit by apical tuft-targeting CA1 neurons. https://doi.org/10.1101/427179

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