During the previous funding period, our laboratory has made great progress identifying and characterizing neural correlates of the recall of stored memories. But an important facet of memory remains almost wholly unknown: the """"""""executive control"""""""" over memory recall. Having identified candidate neural structures and mechanisms, we are now ready to address this issue. In our proposed project, we aim to address the most fundamental question about executive control of recall, its functional organization. To do so, we will compare and contrast the time-course of neural correlates of the recall of task demands with a behavioral measure of recall: switch costs. Switch costs are seen when subjects must flexibly alternate between performing different, often incompatible, judgments and thus must repeatedly recall and update their internal representations of task demands. Switch costs are increases in reaction time (RT) and errors whose magnitude depends on the time between a cue to switch tasks and task initiation. Thus, switch costs reflect the time needed for a set of rules to be recalled from memory and supplant a set of rules already held """"""""on-line"""""""". By comparing neural dynamics of recall with switch costs, we can determine the relationship between this activity and its impact on behavior. We will examine neural activity in brain areas where we have previously identified neural correlates for the recall of task demands: the prefrontal cortex, premotor cortex, and basal ganglia. We found differences in latencies and other neural properties between these areas that suggest different roles in recall. Comparing these properties to a behavioral measure of recall will allow us to tease apart their respective contributions. Monkeys will switch between discriminating the color and orientation; we have already found switch costs in monkeys trained under a similar paradigm. Because executive control over recall and other brain processes is central to intelligent behavior, data from this project has the potential to impact on a wide range of behaviors and human disorders. Executive control is disrupted in a variety of neuropsychiatric disorders such as autism and schizophrenia. By identifying brain structures important for these abilities, discerning their relative roles, and uncovering their neural mechanisms, we can open a path to drug and behavioral therapies designed to alleviate dysfunctions of executive control.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Specialized Center (P50)
Project #
2P50MH058880-06
Application #
6866974
Study Section
Special Emphasis Panel (ZMH1-BRB-S (05))
Project Start
2004-09-01
Project End
2009-06-30
Budget Start
2004-09-01
Budget End
2005-06-30
Support Year
6
Fiscal Year
2004
Total Cost
$103,763
Indirect Cost
Name
Massachusetts Institute of Technology
Department
Type
DUNS #
001425594
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