# Dopaminergic regulation of in vivo plasticity & memory retention

> **NIH NIH R01** · UNIVERSITY OF PENNSYLVANIA · 2020 · $386,299

## Abstract

Cognitive deficits associated with neuronal dysfunction and aging constitute a serious health problem.
Dopaminergic systems contribute to a number of cognitive disorders, such as schizophrenia, Alzheimer's
dementia, and Parkinson's disease, which cost > $200 billion a year in the USA alone. Successful therapeutic
approaches to alleviate cognitive problems should target appropriate neural circuits in the brain. Basic
neuroscience research provides that information necessary to identify the networks, neurotransmitters, and
mechanisms that underlie proper brain function and are the targets for potential therapies. Proper
dopaminergic signaling is essential for cognitive processes such as attention, executive function, learning, and
memory. The complex nature of these processes and the paucity of synaptic and cellular data linked to the
systems-level behaviors have spurred the proposed studies.
Our earlier work showed that induction of in vivo synaptic plasticity associated with a learning task
requires local disinhibition of excitatory circuits coupled with an afferent dopamine signal. Recent results from
our lab support the view that dopamine signaling in the hippocampus lowers the threshold for synaptic
plasticity that underlies learning. Our preliminary results show that local dopaminergic activity is required for in
vivo hippocampal long-term synaptic potentiation associated with diverse learning paradigms, such as aversive
memory retention and novel object recognition. Presently however, there is a controversy regarding the
source, density, and significance of hippocampal dopaminergic innervation and about dopaminergic regulation
of synaptic plasticity and memory. In the proposed studies, we will identify the sources of dopaminergic
neurotransmission in the hippocampus using multiple independent viral labeling methods. Then, we will
examine dopaminergic influences over distinct hippocampal circuits during specific memory tasks. Our working
hypothesis is that dopamine acts within critical time windows and controls the magnitude of synaptic plasticity
within specific circuits that regulate different types of learning. Dopamine normally contributes to the efficient
learning of appropriate behavioral responses motivated by environmental cues. The working hypothesis,
however, also helps to explain the cognitive dysfunctions that arise during dopamine signaling imbalances
found in diseases where inappropriate sensory gating, attention, and learning produce maladaptive behavior.
A multidisciplinary approach that crosses neural levels of integration will be applied to understand the
synaptic mechanisms underlying aversive memory retention and novelty detection. We will use an array of
anatomical tracing and analytical techniques to determine the origin of dopamine signals that act upon
hippocampal circuits. During the performance of behavioral tasks, these endogenous dopaminergic signals will
be temporally controlled using optogenetic approaches, and i...

## Key facts

- **NIH application ID:** 9963382
- **Project number:** 5R01NS021229-36
- **Recipient organization:** UNIVERSITY OF PENNSYLVANIA
- **Principal Investigator:** John A. Dani
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $386,299
- **Award type:** 5
- **Project period:** 1987-09-01 → 2022-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9963382

## Citation

> US National Institutes of Health, RePORTER application 9963382, Dopaminergic regulation of in vivo plasticity & memory retention (5R01NS021229-36). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9963382. Licensed CC0.

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