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 the authors 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 can elicit contextual memory retrieval. To explore network mechanisms, they developed tools to observe cellular-resolution neural activity in the hippocampus while stimulating the projections during memory retrieval in mice behaving in virtual-reality environments. Using this approach, they 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 top-down projection during memory retrieval. These findings are important because they reveal a sparsely implemented memory retrieval mechanism in the hippocampus that operates via direct top-down prefrontal input, with importance for patterning and storage of salient memory representations.
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Rajasethupathy P, Sankaran S, Marshel JH, Kim CK, Ferenczi E, Lee SY, Berndt A, Ramakrishnan C, Jaffe A, Lo M, Liston C and Deisseroth K: Projections from neocortex mediate top-down control of memory retrieval. Nature 526(7575): 653-659 (2015).
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http://www.ncbi.nlm.nih.gov/pubmed/26436451