Application) To understand fully the role of memory in high-order cognition, we must identify mechanisms involved in the reactivating (recalling) of information stored in long-term memory. While much research effort has been devoted to studying the neural mechanisms in the primate brain that hold a recent sensory event temporarily """"""""in mind"""""""" (i.e., in what is known as """"""""working memory""""""""), almost nothing is known about the mechanisms that hold recalled information. Individual Project #3 will contribute to the Center's research objectives by identifying neural mechanisms involved in the recall and storage of long-term memories in the prefrontal and hippocampal system neurons. Elucidation of prefrontal and hippocampal system memory mechanisms is a major target of investigation for the Center. Monkeys are advantageous for studying memory and cognition because they can be trained to perform very complex tasks while rodents are advantageous for genetic manipulations that identify cellular mechanisms. We will test whether recalled long-term memories are maintained by the same mechanisms (and indeed the same neurons) involved in maintaining recent sensory information. This will be achieved by training monkeys to alternate between tasks that can be solved by maintaining sensory information in working memory and tasks that require recall of long-term memories. We will also examine neural activity as monkeys learn associations between stimuli that predicate the ability to recall them from long-term memory. By examining how neural activity evolves during this learning, we will be able to identify structures and mechanisms involved in forming these associations.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Specialized Center (P50)
Project #
5P50MH058880-02
Application #
6346265
Study Section
Special Emphasis Panel (ZMH1)
Project Start
2000-09-01
Project End
2001-08-31
Budget Start
Budget End
Support Year
2
Fiscal Year
2000
Total Cost
$170,164
Indirect Cost
Name
Massachusetts Institute of Technology
Department
Type
DUNS #
City
Cambridge
State
MA
Country
United States
Zip Code
02139
Redondo, Roger L; Kim, Joshua; Arons, Autumn L et al. (2014) Bidirectional switch of the valence associated with a hippocampal contextual memory engram. Nature 513:426-30
Kohara, Keigo; Pignatelli, Michele; Rivest, Alexander J et al. (2014) Cell type-specific genetic and optogenetic tools reveal hippocampal CA2 circuits. Nat Neurosci 17:269-79
Liu, Xu; Ramirez, Steve; Tonegawa, Susumu (2014) Inception of a false memory by optogenetic manipulation of a hippocampal memory engram. Philos Trans R Soc Lond B Biol Sci 369:20130142
Dragoi, George; Tonegawa, Susumu (2013) Development of schemas revealed by prior experience and NMDA receptor knock-out. Elife 2:e01326
Dragoi, George; Tonegawa, Susumu (2013) Distinct preplay of multiple novel spatial experiences in the rat. Proc Natl Acad Sci U S A 110:9100-5
Dolan, Bridget M; Duron, Sergio G; Campbell, David A et al. (2013) Rescue of fragile X syndrome phenotypes in Fmr1 KO mice by the small-molecule PAK inhibitor FRAX486. Proc Natl Acad Sci U S A 110:5671-6
Suh, Junghyup; Foster, David J; Davoudi, Heydar et al. (2013) Impaired hippocampal ripple-associated replay in a mouse model of schizophrenia. Neuron 80:484-93
Buschman, Timothy J; Denovellis, Eric L; Diogo, Cinira et al. (2012) Synchronous oscillatory neural ensembles for rules in the prefrontal cortex. Neuron 76:838-846
Nakashiba, Toshiaki; Cushman, Jesse D; Pelkey, Kenneth A et al. (2012) Young dentate granule cells mediate pattern separation, whereas old granule cells facilitate pattern completion. Cell 149:188-201
Liu, Xu; Ramirez, Steve; Pang, Petti T et al. (2012) Optogenetic stimulation of a hippocampal engram activates fear memory recall. Nature 484:381-5

Showing the most recent 10 out of 32 publications