# The Dopamine Synapse and Associative Learning

> **NIH NIH R01** · COLUMBIA UNIVERSITY HEALTH SCIENCES · 2024 · $472,438

## Abstract

Project Summary/Abstract
Dopamine (DA) neurotransmission in the dorsal striatum and nucleus accumbens has been implicated in drug
seeking and reward since the 1950s, when it was shown to mediate the effects of cocaine and opiates. However,
our and other’s recent work has shown that DA also plays a role in another circuitry critical for drug dependence.
Within the rostral striatum (tail of the striatum: TS) – the central locus where auditory DA, cortical and thalamic
axons converge to control auditory learning – DA neurotransmission is necessary for learned association of a
sound with a behavior, such as drug self-administration. To address this role for DA, we have developed novel
technical approaches that allow us to measure activity and neuronal signaling during associative learning and
recall tests, and then to correlate changes in animal behavior and in vivo synaptic activity with detailed ex vivo
analysis after learning. These experiments have led to the identification of a new form of synaptic plasticity that
occurs at auditory thalamic inputs to the TS projection neurons, consisting of a simultaneous decrease in overall
activity with a concurrent increase in response to a specific sound cue. This form of enhanced signal-to-noise
response by specific synapses may provide a basis of sensory cue learning. This project tests i) the precise
physiological and molecular steps required for auditory sensory learning; ii) the role played by the TS dopamine
and glutamate neurotransmission in this form of learning and synaptic plasticity, and iii) a role of DA in “refining”
TS synaptic circuits in order to allow further learning. These experiments promise to unveil the molecular steps
responsible for the action of addictive drugs such as amphetamine and opiates that drive self-administration,
and will further be important for understanding language disorders, hallucinations and affective disorders
including ADHD and PTSD.

## Key facts

- **NIH application ID:** 10803867
- **Project number:** 2R01DA007418-29
- **Recipient organization:** COLUMBIA UNIVERSITY HEALTH SCIENCES
- **Principal Investigator:** David Sulzer
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $472,438
- **Award type:** 2
- **Project period:** 1991-07-01 → 2028-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10803867

## Citation

> US National Institutes of Health, RePORTER application 10803867, The Dopamine Synapse and Associative Learning (2R01DA007418-29). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10803867. Licensed CC0.

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