Precise neuromodulation for encoding reward in the hippocampus

NIH RePORTER · NIH · R01 · $396,095 · view on reporter.nih.gov ↗

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
STANFORD UNIVERSITY
Principal Investigator
Lisa Giocomo
Activity code
R01
Funding institute
NIH
Fiscal year
2023
Award amount
$396,095
Award type
5
Project period
2022-08-26 → 2027-06-30