title: Transgenically targeted rabies virus demonstrates a major monosynaptic projection from hippocampal area CA2 to medial entorhinal layer II neurons.
abstract: The enormous potential of modern molecular neuroanatomical tools lies in their ability to determine the precise connectivity of the neuronal cell types comprising the innate circuitry of the brain. We used transgenically targeted viral tracing to identify the monosynaptic inputs to the projection neurons of layer II of medial entorhinal cortex (MEC-LII) in mice. These neurons are not only major inputs to the hippocampus, the structure most clearly implicated in learning and memory, they also are "grid cells." Here we address the question of what kinds of inputs are specifically targeting these MEC-LII cells. Cell-specific infection of MEC-LII with recombinant rabies virus results in unambiguous labeling of monosynaptic inputs. Furthermore, ratios of labeled neurons in different regions are largely consistent between animals, suggesting that label reflects density of innervation. While the results mostly confirm prior anatomical work, they also reveal a novel major direct input to MEC-LII from hippocampal pyramidal neurons. Interestingly, the vast majority of these direct hippocampal inputs arise not from the major hippocampal subfields of CA1 and CA3, but from area CA2, a region that has historically been thought to merely be a transitional zone between CA3 and CA1. We confirmed this unexpected result using conventional tracing techniques in both rats and mice.
authors.affiliation: University of Oregon, Institute of Neuroscience, Eugene, Oregon 97403, Massachusetts Institute of Technology, Department of Brain and Cognitive Sciences, Cambridge, Massachusetts 02139, The Scripps Research Institute, Department of Cell Biology, La Jolla, California 92037, and Norwegian University of Science and Technology, Kavli Institute for Systems Neuroscience and Centre for Neural Computation, 7491 Trondheim, Norway.
authors.forename: David C
authors.initials: DC
authors.lastname: Rowland
authors.forename: Aldis P
authors.initials: AP
authors.lastname: Weible
authors.forename: Ian R
authors.initials: IR
authors.lastname: Wickersham
authors.forename: Haiyan
authors.initials: H
authors.lastname: Wu
authors.forename: Mark
authors.initials: M
authors.lastname: Mayford
authors.forename: Menno P
authors.initials: MP
authors.lastname: Witter
authors.forename: Clifford G
authors.initials: CG
authors.lastname: Kentros
mesh_terms: D000818:Animals; D001931:Brain Mapping; D056651:CA2 Region, Hippocampal / Q000166:cytology* / Q000502:physiology; D002452:Cell Count; D018728:Entorhinal Cortex / Q000166:cytology / Q000502:physiology*; D006801:Humans; D008164:Luminescent Proteins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D009434:Neural Pathways / Q000502:physiology*; D011820:Rabies virus / Q000235:genetics; D014759:Viral Envelope Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: D008164:Luminescent Proteins; D014759:Viral Envelope Proteins
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