The abilities to learn, remember, evaluate and decide are central to who we are and how we structure our lives. These abilities, and indeed the vast majority of cognitive functions, are thought to depend on specific patterns of brain activity. Each new experience is thought to drive a unique pattern of brain activity in the hippocampus, a brain region critical for storing memories for the events of daily life. Subsequent reactivation of this experience after learning is thought to drive a consolidation process that engrains the patterns in hippocampal and cortical circuits. Similarly, subsequent retrieval is thought to rely on the reinstatement of patterns similar to those present during the original experience. Current evidence points to the replay of sequences of hippocampal neurons during sharp-wave ripple events (SWRs) as a candidate mechanism for both memory consolidation and memory retrieval. To determine whether memory replay drives consolidation and retrieval for the associated memory representations, we will carry out directed manipulations that go beyond interrupting all SWRs to target replay events by their content. Our work will build on our expertise in real-time feedback and recent developments in cluster-less decoding that have allowed us to develop all of the technological elements required for real-time, content-based interruption of hippocampal replay events. This will allow us to assess the role of specific memory replay events in memory processes.
Our Specific Aims are: 1) to develop an optimal adaptive statistical framework for real-time decoding and interruption of memory replay, 2) to test the hypothesis that hippocampal replay events drive memory consolidation for the replayed memories, and 3) to test the hypothesis that hippocampal replay events support rule learning and the internal exploration of specific future possibilities. Our real-time approach has the potential to create new causal links between the replay of specific patterns of activity and the ability to consolidation memories and to use past experience to guide future decisions.

Public Health Relevance

The abilities to learn, remember, evaluate and decide are central to who we are and how we structure our lives. These abilities, and indeed the vast majority of cognitive functions, are thought to depend on specific patterns of brain activity. Our goal here is to understand how the replay of specific neural sequences in the hippocampus, a brain structure critical for memory storage and retrieval, contributes to different memory processes.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Research Project (R01)
Project #
1R01MH105174-01
Application #
8787330
Study Section
Special Emphasis Panel (ZRG1-IFCN-T (02))
Program Officer
Osborn, Bettina D
Project Start
2014-08-01
Project End
2019-06-30
Budget Start
2014-08-01
Budget End
2015-06-30
Support Year
1
Fiscal Year
2014
Total Cost
$674,289
Indirect Cost
$157,610
Name
University of California San Francisco
Department
Physiology
Type
Schools of Medicine
DUNS #
094878337
City
San Francisco
State
CA
Country
United States
Zip Code
94143