# Synaptic Microcircuits Underlying Associative Learning

> **NIH NIH R01** · YALE UNIVERSITY · 2020 · $408,739

## Abstract

Animals learn to associate otherwise neutral sensory cues with positive or negative contingencies and rely
on those associations to make adaptive decisions. Flexible updating of these acquired associations as
contingencies change is also important. Failure to update internal representations plays a causal role in some
mental disorders, including schizophrenia and anxiety. While the neural substrates of acquiring and updating
associations have been studied in mammalian models, the complexity of the mammalian brain has made it
difficult to obtain precise cellular and synaptic mechanistic understanding. Drosophila flies exhibit flexible
associative learning: they learn to avoid an odor paired with electric shock, and extinguish that learned
association when the odor is later presented without shock. Flies have powerful genetic tools to allow precise
manipulation and visualization of neural activity with cellular resolution in the mushroom body brain region
(MB), where neural plasticity underlying learning occurs. Our long-term goal is to use Drosophila to gain
mechanistic insight into how acquisition and extinction are implemented by synaptic microcircuits of the MB.
Our novel hypothesis is that plasticity of dopamine neurons embedded in a recurrent synaptic microcircuit
residing in the fly mushroom body underlies extinction of odor-shock associations. To test this hypothesis we
employ in vivo Ca2+ imaging and optogenetics to visualize and manipulate dynamic changes in neural activity
of specific genetically targeted MB cell types as a fly acquires and extinguishes an association between a neutral
odor and aversive electric shock.

## Key facts

- **NIH application ID:** 10051761
- **Project number:** 2R01NS091070-06
- **Recipient organization:** YALE UNIVERSITY
- **Principal Investigator:** Michael Nitabach
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $408,739
- **Award type:** 2
- **Project period:** 2014-09-30 → 2025-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10051761

## Citation

> US National Institutes of Health, RePORTER application 10051761, Synaptic Microcircuits Underlying Associative Learning (2R01NS091070-06). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10051761. Licensed CC0.

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