# Precise neuromodulation for encoding reward in the hippocampus

> **NIH NIH R01** · STANFORD UNIVERSITY · 2023 · $396,095

## Abstract

Accumulating research has revealed that computations of reward and its prediction occur on multiple levels
across a complex set of interacting brain regions, including those that support memory and navigation. Yet how
the brain coordinates the encoding, recall and use of reward information to guide navigation and memory remains
incompletely understood. Here, we focus on the mechanisms for encoding reward in the hippocampus, a medial
temporal lobe structure that serves a key role in supporting navigation and memory. In the hippocampus, place
cells fire in one or few restricted spatial locations, providing an internal neural representation of the external
world. Place cells are also strongly modulated by reward. For example, place fields (the location where a place
cell is maximally active) cluster near reward locations, resulting in an overrepresentation of those locations.
However, the circuit and cellular mechanisms by which reward controls place cell representations remains
unknown. We propose to examine how the precise spatial and temporal dynamics of dopamine and
norepinephrine control hippocampal representations at the level of individual place cells. In our first aim, we will
perform simultaneous 2-photon imaging of calcium signals and dopamine or norepinephrine signals in CA1
neurons as animals navigate through virtual environments. We will test the hypotheses that dopamine – in
coordination with norepinephrine – can drive place cell representations near rewarded locations and temporally
gate place cell representations to provide a signal for reward certainty. In our second aim, we will use the same
technical approach to test the hypothesis that dopamine and norepinephrine act as a gating mechanisms for the
detection of novelty and determine the temporal dynamics of neuromodulatory-driven novelty detection signals
to the hippocampus. In our final aim, we will examine how the ventral tegmental area and locus coeruleus, which
release dopamine and norepinephrine, mediate CA1 place cells and drive reward-driven place cell
representations. Together, this work will provide new insight regarding the mechanisms of reward-driven
changes to hippocampal representations at a spatial and temporal resolution technical innovations have only
recently made possible. Moreover, this work will establish an approach and framework for future work examining
how neuromodulators control hippocampal representations.

## Key facts

- **NIH application ID:** 10691346
- **Project number:** 5R01MH130452-02
- **Recipient organization:** STANFORD UNIVERSITY
- **Principal Investigator:** Lisa Giocomo
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $396,095
- **Award type:** 5
- **Project period:** 2022-08-26 → 2027-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10691346

## Citation

> US National Institutes of Health, RePORTER application 10691346, Precise neuromodulation for encoding reward in the hippocampus (5R01MH130452-02). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/10691346. Licensed CC0.

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