Projections from neocortex mediate top-down control of memory retrieval.

Publication Type	Academic Article
Authors	Rajasethupathy P, Sankaran S, Marshel J, Kim C, Ferenczi E, Lee S, Berndt A, Ramakrishnan C, Jaffe A, Lo M, Liston C, Deisseroth K
Journal	Nature
Volume	526
Issue	7575
Pagination	653-9
Date Published	10/05/2015
ISSN	1476-4687
Keywords	Memory, Neocortex, Neural Pathways
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.
DOI	10.1038/nature15389
PubMed ID	26436451
PubMed Central ID	PMC4825678