# Real-time manipulations to understand and improve memory processes

> **NIH NIH K99** · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · 2021 · $117,417

## Abstract

PROJECT SUMMARY/ABSTRACT
The hippocampus is critical for capturing rich, multimodal representations of experience and facilitating
the long-term storage and later recall of these experiences. During sleep and pauses in behavior, the
hippocampus can “replay” prior experience – reactivating the neural ensemble corresponding to the
original experience in a time-compressed manner. During sleep, such replay is thought to underlie
memory consolidation, while during behavior, replay is thought to additionally serve a more prospective
role: contributing to planning or deliberation by retrieving stored memories in order to inform upcoming
decisions. However, the content of replay neither solely reflects recent experience nor reliably predicts
future behavior, leaving it unclear how exactly the representations of experience that are replayed relate
to upcoming choices. Understanding the relationship between replay and behavior is particularly critical
because abnormalities in replay and sharp wave ripples (SWRs; the network activity signature of replay)
have been observed concurrent with impaired memory-dependent behavior in aging and diseases of
aging. Establishing how replay content changes with aging, and whether these changes cause deficits in
memory-guided behavior, has the potential to generate new therapeutic strategies to prevent or reverse
memory impairment. In order to define how replay contributes to memory-guided decision-making in
normal cognition and in the context of age-related memory impairment, we have developed a
neurofeedback-based operant conditioning paradigm that targets SWRs. This paradigm provides rapid
feedback contingent upon real-time detection of SWRs at a specific point during each trial of a spatial
memory task, and results in substantially increased occurrence of SWRs in a trial phase- specific manner.
Consequently, subjects experience more replay at the required trial phase, which occurs immediately
prior to the choice point of a memory-dependent task. In addition to demonstrating that replay can be
enhanced by neurofeedback, this behavioral paradigm provides an increased opportunity to link the
content of replay with subsequent behavior. This paradigm lays the foundation for the three aims of this
proposal: to define the relationship between replay and memory-guided behavior, to assess how this
relationship changes with age, and to adapt the operant conditioning strategy to directly counter age-
related replay dysfunction. I will complete these aims with the guidance of an exceptional mentoring team
led by Loren Frank and including Carol Barnes, Uri Eden, and Karunesh Ganguly. During the mentored
phase of the award at UCSF, I will conduct the proposed real-time feedback studies, gain expertise in
using state-space models to capture and quantify replay content, scale experiments to efficiently examine
larger cohorts of young and aged animals, and focus on professional development in order to facilitate a
successful transiti...

## Key facts

- **NIH application ID:** 10159187
- **Project number:** 5K99AG068425-02
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
- **Principal Investigator:** Anna Kathleen Gillespie
- **Activity code:** K99 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $117,417
- **Award type:** 5
- **Project period:** 2020-05-15 → 2022-12-29

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10159187

## Citation

> US National Institutes of Health, RePORTER application 10159187, Real-time manipulations to understand and improve memory processes (5K99AG068425-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10159187. Licensed CC0.

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