# Activity-dependent mechanisms for memory circuit maturation.

> **NIH NIH R00** · GEORGE WASHINGTON UNIVERSITY · 2023 · $249,000

## Abstract

PROJECT SUMMARY
Adult behavior is the product of neural circuits that have been sculpted during development by
genetic programs and experience in the form of neural activity. Developing nervous systems
frequently display characteristic spontaneous activity that is essential for circuit refinement.
However, the precise mechanisms by which spontaneous neural activity sculpts the refinement
and maturation of non-sensorimotor circuits to shape behavior remain poorly understood. The
Drosophila mushroom body, with its well characterized anatomy and well-established role in
learned behavior, is an ideal system for causally investigating the developmental maturation of
higher order neural circuits. The goal of this proposal is to identify mechanisms for the
maturation of spontaneous and evoked neural activity to support adult learned behavior. In
preliminary studies, I discovered spontaneous, asynchronous oscillatory activity in Kenyon
cells, the principal intrinsic neurons of the mushroom body, specifically in very young adult
flies, which declines significantly over the first week of adulthood. Our results suggest that
Kenyon cell activity in young adult development is required for subsequent expression of
robust learned behavior in the mature adult. Moreover, I identified Juvenile Hormone as a
critical regulator of the maturation of Kenyon cell spontaneous activity in early adulthood. A
multifaceted approach employing molecular genetics, learned behavioral analysis and state of
the art functional calcium imaging is proposed to (1) characterize Juvenile Hormone effector
genes that regulate the maturation of Kenyon cell spontaneous neural activity over the first
week of adulthood and (2) dissect the role of hormonal signaling in the maturation of
associative learning behavior. In the independent phase, we will (3) investigate how
conditioned odor-evoked neural activity matures over the first week of adulthood in Kenyon cell
circuits, improving our understanding of the neural substrates for learned behavior. To achieve
these goals, I will pursue comprehensive training in learned behavioral assays, state of the art
volumetric imaging technologies and computational neuroscience methods. My primary mentor
Dr. Kristin Scott, my Scientific Advisory Committee and Consultants, and the UC Berkeley
environment provide stellar opportunities for my scientific growth and professional
development, uniquely preparing me to launch a successful independent scientific career.
These efforts will lead to significant insights into the fundamentally important question of
activity-dependent maturation of neural circuits and learned behavior.

## Key facts

- **NIH application ID:** 10759557
- **Project number:** 4R00DC018779-03
- **Recipient organization:** GEORGE WASHINGTON UNIVERSITY
- **Principal Investigator:** Sarah Leinwand
- **Activity code:** R00 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $249,000
- **Award type:** 4N
- **Project period:** 2020-08-01 → 2023-12-20

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10759557

## Citation

> US National Institutes of Health, RePORTER application 10759557, Activity-dependent mechanisms for memory circuit maturation. (4R00DC018779-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10759557. Licensed CC0.

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