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 onto M2 pyramidal 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.



Corticocortical pathways interconnect cortical areas extensively, but the cellular connectivity in these pathways remains largely uncharacterized. Here, we show that a posterior part of secondary motor cortex receives corticocortical axons from the rostral retrosplenial cortex (RSC) and these form monosynaptic excitatory connections onto a wide spectrum of excitatory projection neurons in this area. Our results define a cellular basis for direct communication from RSC to this medial frontal area, suggesting a direct link from dorsal hippocampal networks involved in spatial cognition and navigation (the "map") to sensorimotor networks involved the control of movement (the "motor").
Department of Physiology and yamawakn@gmail.com gmgshepherd@gmail.com.
Naoki
N
Yamawaki
Department of Psychology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois 60611.
Jelena
0000-0002-0268-2426
J
Radulovic
Department of Physiology and yamawakn@gmail.com gmgshepherd@gmail.com.
Gordon M G
0000-0002-1455-8262
GM
Shepherd
D000818:Animals; D000075402:Channelrhodopsins; D002772:Cholera Toxin / Q000378:metabolism; D005260:Female; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D066298:In Vitro Techniques; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009044:Motor Cortex / Q000166:cytology*; D009415:Nerve Net / Q000502:physiology*; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D018377:Neurotransmitter Agents / Q000494:pharmacology; D062308:Optogenetics; D010296:Parietal Lobe / Q000166:cytology*; D018408:Patch-Clamp Techniques; D011712:Pyramidal Tracts / Q000502:physiology*; D014161:Transduction, Genetic
D000075402:Channelrhodopsins; D018377:Neurotransmitter Agents; C485184:enhanced green fluorescent protein; D049452:Green Fluorescent Proteins; D002772:Cholera Toxin
circuit; motor; neocortex; optogenetic; retrosplenial