Projections from neocortex mediate top-down control of memory retrieval. 2015

Priyamvada Rajasethupathy, and Sethuraman Sankaran, and James H Marshel, and Christina K Kim, and Emily Ferenczi, and Soo Yeun Lee, and Andre Berndt, and Charu Ramakrishnan, and Anna Jaffe, and Maisie Lo, and Conor Liston, and Karl Deisseroth
Department of Bioengineering, Stanford University, Stanford, California 94305, USA.

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.

UI MeSH Term Description Entries
D007858 Learning Relatively permanent change in behavior that is the result of past experience or practice. The concept includes the acquisition of knowledge. Phenomenography
D008297 Male Males
D008568 Memory Complex mental function having four distinct phases: (1) memorizing or learning, (2) retention, (3) recall, and (4) recognition. Clinically, it is usually subdivided into immediate, recent, and remote memory.
D008810 Mice, Inbred C57BL One of the first INBRED MOUSE STRAINS to be sequenced. This strain is commonly used as genetic background for transgenic mouse models. Refractory to many tumors, this strain is also preferred model for studying role of genetic variations in development of diseases. Mice, C57BL,Mouse, C57BL,Mouse, Inbred C57BL,C57BL Mice,C57BL Mice, Inbred,C57BL Mouse,C57BL Mouse, Inbred,Inbred C57BL Mice,Inbred C57BL Mouse
D008959 Models, Neurological Theoretical representations that simulate the behavior or activity of the neurological system, processes or phenomena; includes the use of mathematical equations, computers, and other electronic equipment. Neurologic Models,Model, Neurological,Neurologic Model,Neurological Model,Neurological Models,Model, Neurologic,Models, Neurologic
D009434 Neural Pathways Neural tracts connecting one part of the nervous system with another. Neural Interconnections,Interconnection, Neural,Interconnections, Neural,Neural Interconnection,Neural Pathway,Pathway, Neural,Pathways, Neural
D009474 Neurons The basic cellular units of nervous tissue. Each neuron consists of a body, an axon, and dendrites. Their purpose is to receive, conduct, and transmit impulses in the NERVOUS SYSTEM. Nerve Cells,Cell, Nerve,Cells, Nerve,Nerve Cell,Neuron
D003213 Conditioning, Psychological Simple form of learning involving the formation, strengthening, or weakening of an association between a stimulus and a response. Conditioning, Psychology,Psychological Conditioning,Social Learning Theory,Social Learning Theories,Theory, Social Learning
D005239 Fear The affective response to an actual current external danger which subsides with the elimination of the threatening condition. Threat Cues,Threat Sensitivity,Cue, Threat,Fears,Sensitivity, Threat,Threat Cue,Threat Sensitivities
D006179 Gyrus Cinguli One of the convolutions on the medial surface of the CEREBRAL HEMISPHERES. It surrounds the rostral part of the brain and CORPUS CALLOSUM and forms part of the LIMBIC SYSTEM. Anterior Cingulate Gyrus,Brodmann Area 23,Brodmann Area 24,Brodmann Area 26,Brodmann Area 29,Brodmann Area 30,Brodmann Area 31,Brodmann Area 32,Brodmann Area 33,Brodmann's Area 23,Brodmann's Area 24,Brodmann's Area 26,Brodmann's Area 29,Brodmann's Area 30,Brodmann's Area 31,Brodmann's Area 32,Brodmann's Area 33,Cingulate Gyrus,Gyrus Cinguli Anterior,Retrosplenial Complex,Retrosplenial Cortex,Anterior Cingulate,Anterior Cingulate Cortex,Cingular Gyrus,Cingulate Area,Cingulate Body,Cingulate Cortex,Cingulate Region,Gyrus, Cingulate,Posterior Cingulate,Posterior Cingulate Cortex,Posterior Cingulate Gyri,Posterior Cingulate Gyrus,Posterior Cingulate Region,Superior Mesial Regions,24, Brodmann Area,Anterior Cingulate Cortices,Anterior Cingulates,Anterior, Gyrus Cinguli,Anteriors, Gyrus Cinguli,Area 23, Brodmann,Area 23, Brodmann's,Area 24, Brodmann,Area 24, Brodmann's,Area 26, Brodmann,Area 26, Brodmann's,Area 29, Brodmann,Area 29, Brodmann's,Area 30, Brodmann,Area 30, Brodmann's,Area 31, Brodmann,Area 31, Brodmann's,Area 32, Brodmann,Area 32, Brodmann's,Area 33, Brodmann,Area 33, Brodmann's,Area, Cingulate,Body, Cingulate,Brodmanns Area 23,Brodmanns Area 24,Brodmanns Area 26,Brodmanns Area 29,Brodmanns Area 30,Brodmanns Area 31,Brodmanns Area 32,Brodmanns Area 33,Cingulate Areas,Cingulate Bodies,Cingulate Cortex, Anterior,Cingulate Cortex, Posterior,Cingulate Gyrus, Anterior,Cingulate Gyrus, Posterior,Cingulate Region, Posterior,Cingulate Regions,Cingulate, Anterior,Cingulate, Posterior,Cinguli Anterior, Gyrus,Cinguli Anteriors, Gyrus,Complex, Retrosplenial,Cortex, Anterior Cingulate,Cortex, Cingulate,Cortex, Posterior Cingulate,Cortex, Retrosplenial,Gyrus Cinguli Anteriors,Gyrus, Anterior Cingulate,Gyrus, Cingular,Gyrus, Posterior Cingulate,Posterior Cingulate Cortices,Posterior Cingulate Regions,Posterior Cingulates,Region, Cingulate,Region, Posterior Cingulate,Retrosplenial Complices,Retrosplenial Cortices,Superior Mesial Region

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