# Mechanisms of adult forebrain neural circuit regeneration

> **NIH NIH R01** · UNIVERSITY OF WASHINGTON · 2021 · $573,788

## Abstract

Project Summary:
The neural circuit that regulates birdsong, a highly precise, learned sensorimotor behavior, excels for study of
fundamental mechanisms of adult circuit plasticity. The song system is a unique model of naturally occurring
degeneration and compensatory regeneration in a behaviorally relevant neural circuit in adult brains. This
circuit shows exaggerated seasonal degeneration and reconstruction via neurogenesis, in response to
changes in circulating steroid hormone levels. Our long-term goal is to understand the fundamental
mechanisms by which steroid hormones and neurotrophins interact to regulate plasticity of neural circuits and
behavior. On a translational level, our goal is to understand how forebrain circuits can regenerate to support
performance of complex learned motor skills. The central hypothesis of the proposed aims is that seasonal
changes in hormones trigger changes in anterograde and retrograde trophic signaling that lead to remodeling
of the HVC-RA circuit and changes in song behavior in adult birds.The goal of this application is to identify the
trophic signaling pathways (molecular and electrophysiological) that regulate the the incorporation of newborn
neurons to regenerate this circuit. This research will advance the field by elucidating fundamental issues of
adult circuit plasticity. This topic is of translational relevance for exploiting endogenous or exogenous stem
cells for therapeutic repair of injured or dysfunctional circuits in humans. These fundamental issues include
whether new neurons added to adult circuits establish functional connections with efferent nuclei and restore
behavior (Aim 1), the role of activity regulated genes in mediating retrograde trophic effects of neuronal activity
on presynaptic adult neurogenesis (Aim 2), the role of calcium channels in mediating the transsynaptic
neurotrophic regulation of postsynaptic activity (Aim 3), and the role of pre- and/or postsynaptic neuronal
activity in maintaining a regenerated adult circuit (Aim 4).

## Key facts

- **NIH application ID:** 10112966
- **Project number:** 5R01NS103973-04
- **Recipient organization:** UNIVERSITY OF WASHINGTON
- **Principal Investigator:** ELIOT A BRENOWITZ
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $573,788
- **Award type:** 5
- **Project period:** 2018-05-15 → 2023-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10112966

## Citation

> US National Institutes of Health, RePORTER application 10112966, Mechanisms of adult forebrain neural circuit regeneration (5R01NS103973-04). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10112966. Licensed CC0.

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