Dynamics of retrieval strategies for remote memories

Inbal Goshen, Matthew Brodsky, Rohit Prakash, Jenelle Wallace, Viviana Gradinaru, Charu Ramakrishnan, Karl Deisseroth*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

425 Scopus citations

Abstract

Prevailing theory suggests that long-term memories are encoded via a two-phase process requiring early involvement of the hippocampus followed by the neocortex. Contextual fear memories in rodents rely on the hippocampus immediately following training but are unaffected by hippocampal lesions or pharmacological inhibition weeks later. With fast optogenetic methods, we examine the real-time contribution of hippocampal CA1 excitatory neurons to remote memory and find that contextual fear memory recall, even weeks after training, can be reversibly abolished by temporally precise optogenetic inhibition of CA1. When this inhibition is extended to match the typical time course of pharmacological inhibition, remote hippocampus dependence converts to hippocampus independence, suggesting that long-term memory retrieval normally depends on the hippocampus but can adaptively shift to alternate structures. Further revealing the plasticity of mechanisms required for memory recall, we confirm the remote-timescale importance of the anterior cingulate cortex (ACC) and implicate CA1 in ACC recruitment for remote recall.

Original languageAmerican English
Pages (from-to)678-689
Number of pages12
JournalCell
Volume147
Issue number3
DOIs
StatePublished - 28 Oct 2011
Externally publishedYes

Bibliographical note

Funding Information:
We thank the entire Deisseroth laboratory for their support. K.D. is supported by the Gatsby Charitable Foundation and the Keck, Snyder, Woo, Yu, and McKnight Foundations, as well as by CIRM, NIMH, NINDS, NIDA, and the DARPA REPAIR program. I.G. is supported by the Machiah Foundation and the Weizmann Institute of Science National Postdoctoral Award Program for Advancing Women in Science, R.P. is supported by the NIH, J.W. is supported by the BioX undergraduate summer research program, and V.G. by the Stanford Graduate Fellowship program.

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