title: Projections from neocortex mediate top-down control of memory retrieval.
abstract: Top-down prefrontal cortex inputs to the hippocampus have been hypothesized to be important in memory consolidation, retrieval, and the pathophysiology of major psychiatric diseases; however, no such direct projections have been identified and functionally described. Here we report the discovery of a monosynaptic prefrontal cortex (predominantly anterior cingulate) to hippocampus (CA3 to CA1 region) projection in mice, and find that optogenetic manipulation of this projection (here termed AC-CA) is capable of eliciting contextual memory retrieval. To explore the network mechanisms of this process, we developed and applied tools to observe cellular-resolution neural activity in the hippocampus while stimulating AC-CA projections during memory retrieval in mice behaving in virtual-reality environments. Using this approach, we found that learning drives the emergence of a sparse class of neurons in CA2/CA3 that are highly correlated with the local network and that lead synchronous population activity events; these neurons are then preferentially recruited by the AC-CA projection during memory retrieval. These findings reveal a sparsely implemented memory retrieval mechanism in the hippocampus that operates via direct top-down prefrontal input, with implications for the patterning and storage of salient memory representations.
authors.affiliation: Department of Bioengineering, Stanford University, Stanford, California 94305, USA.|CNC Program, Stanford University, Stanford, California 94305, USA.
authors.forename: Priyamvada
authors.initials: P
authors.lastname: Rajasethupathy
authors.affiliation: CNC Program, Stanford University, Stanford, California 94305, USA.
authors.forename: Sethuraman
authors.initials: S
authors.lastname: Sankaran
authors.affiliation: Department of Bioengineering, Stanford University, Stanford, California 94305, USA.
authors.forename: James H
authors.initials: JH
authors.lastname: Marshel
authors.affiliation: Department of Bioengineering, Stanford University, Stanford, California 94305, USA.|Neuroscience Program, Stanford University, Stanford, California 94305, USA.
authors.forename: Christina K
authors.initials: CK
authors.lastname: Kim
authors.affiliation: Department of Bioengineering, Stanford University, Stanford, California 94305, USA.|Neuroscience Program, Stanford University, Stanford, California 94305, USA.
authors.forename: Emily
authors.initials: E
authors.lastname: Ferenczi
authors.affiliation: Department of Bioengineering, Stanford University, Stanford, California 94305, USA.|Neuroscience Program, Stanford University, Stanford, California 94305, USA.
authors.forename: Soo Yeun
authors.initials: SY
authors.lastname: Lee
authors.affiliation: Department of Bioengineering, Stanford University, Stanford, California 94305, USA.|Neuroscience Program, Stanford University, Stanford, California 94305, USA.
authors.forename: Andre
authors.initials: A
authors.lastname: Berndt
authors.affiliation: Department of Bioengineering, Stanford University, Stanford, California 94305, USA.
authors.forename: Charu
authors.initials: C
authors.lastname: Ramakrishnan
authors.affiliation: Department of Bioengineering, Stanford University, Stanford, California 94305, USA.
authors.forename: Anna
authors.initials: A
authors.lastname: Jaffe
authors.affiliation: Department of Bioengineering, Stanford University, Stanford, California 94305, USA.
authors.forename: Maisie
authors.initials: M
authors.lastname: Lo
authors.affiliation: Department of Bioengineering, Stanford University, Stanford, California 94305, USA.|Department of Psychiatry and Behavioral Sciences, Stanford University, Stanford, California 94305, USA.
authors.forename: Conor
authors.initials: C
authors.lastname: Liston
authors.affiliation: Department of Bioengineering, Stanford University, Stanford, California 94305, USA.|CNC Program, Stanford University, Stanford, California 94305, USA.|Department of Psychiatry and Behavioral Sciences, Stanford University, Stanford, California 94305, USA.|Howard Hughes Medical Institute, Stanford University, Stanford, California 94305, USA.
authors.forename: Karl
authors.initials: K
authors.lastname: Deisseroth
mesh_terms: D000818:Animals; D003213:Conditioning, Psychological; D005239:Fear; D006179:Gyrus Cinguli / Q000502:physiology; D006624:Hippocampus / Q000166:cytology / Q000502:physiology; D007858:Learning / Q000502:physiology; D008297:Male; D008568:Memory / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008959:Models, Neurological; D019579:Neocortex / Q000166:cytology* / Q000502:physiology*; D009434:Neural Pathways / Q000502:physiology*; D009474:Neurons / Q000502:physiology; D062308:Optogenetics; D017397:Prefrontal Cortex / Q000502:physiology; D014584:User-Computer Interface