# Investigating neural substrates of generalization from past experience

> **NIH NIH F30** · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · 2021 · $38,220

## Abstract

PROJECT SUMMARY/ABSTRACT:
In new settings, we have a remarkable ability to generalize from prior learning to help us achieve our goals. This
capacity is thought to depend on our ability to represent the common relationships present in related experiences,
such as the series of steps involved in grocery shopping at any one of a variety of supermarkets. These context-
generalized representations of a task have been termed schemas. In the brain, schemas are thought to be
represented by neural ensembles that encode a task similarly across contexts. Recent work has identified
schema representations in the prefrontal cortex (PFC). How these schema representations form and support
rapid learning in new contexts, however, is not well understood.
A well-established theory of long-term memory formation known as systems consolidation theory provides a
model for how schema representations may arise in the brain. According to this theory, the hippocampus (HPc)
rapidly encodes memories of specific episodes in new contexts. In periods of rest that follow, these HPc
memories are reactivated, and this is thought to result in the long-lasting strengthening of corresponding memory
traces within and across neocortex. The resulting neocortical memories are thought to emphasize common
features across contexts, providing a basis for schema representation. Our overarching hypothesis based on the
theory of systems consolidation is that HPc memory reactivation promotes the formation of schema
representations in PFC (Aims 1 and 3), and expression of these representations in new contexts in turn enables
rapid learning (Aims 2 and 3). To test this hypothesis, we will pair a rat model of learning in new contexts wherein
rats exhibit rapid learning given prior experience, with simultaneous recordings of PFC and HPc neural
ensembles (Aims 1–3) and causal intervention studies (Aim 3).
Completion of these Aims has the potential to yield fundamental insights into the neural substrates of
generalization from past experience. Our findings will additionally provide important evidence for or against
longstanding predictions of systems consolidation theory that have so far been difficult to test in the absence of
distributed simultaneous recordings. This study will be carried out in the lab of my research sponsor, Dr. Loren
Frank, at the University of California, San Francisco (UCSF). The Frank lab is located in Sandler Neurosciences
Center, which is home to a highly innovative and collaborative community of faculty and students pursuing
neuroscience questions. My training plan under this fellowship will prepare me for an independent career as an
academic physician scientist with the long-term goal of revealing neural computations underlying cognitive
processes. In addition to the proposed research, this preparation will be achieved through rigorous quantitative
coursework, planned engagement with vibrant intellectual communities, and clinically geared activities.

## Key facts

- **NIH application ID:** 10389027
- **Project number:** 1F30MH126483-01A1
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
- **Principal Investigator:** Jennifer Ann Guidera
- **Activity code:** F30 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $38,220
- **Award type:** 1
- **Project period:** 2021-09-01 → 2025-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10389027

## Citation

> US National Institutes of Health, RePORTER application 10389027, Investigating neural substrates of generalization from past experience (1F30MH126483-01A1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10389027. Licensed CC0.

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