# A Dendritic Substrate for Fast-Acting Antidepressant Action

> **NIH NIH R01** · YALE UNIVERSITY · 2020 · $567,043

## Abstract

PROJECT SUMMARY
 Our long-term goal is to understand how the structure and function of dendrites in the frontal cortex are
affected by stress and antidepressants. Considerable evidence indicates that the action of fast-acting
antidepressants such as ketamine relies on synaptic plasticity in the frontal cortex. An essential ingredient for
plasticity is calcium influx in dendritic spines. However, to date, empirical data detailing how antidepressants
may modulate calcium levels in dendritic spines in vivo are lacking. In preliminary studies, we used subcellular-
resolution two-photon microscopy to visualize localized calcium transients in dendritic spines in the medial
frontal cortex of the mouse in vivo. We found that the administration of the fast-acting antidepressant ketamine
leads to an acute elevation of calcium signals in apical dendritic spines, due to a suppression of dendritic
inhibition. On the basis of the preliminary results and prior research, we hypothesize that the enhanced
synaptic calcium signal is a necessary step towards ketamine’s antidepressant action. In this project, we will
determine the interactive effects of stress and ketamine on synaptic calcium signals (Aim 1). We will track
morphology and calcium signals in the same dendritic spines to ask if the calcium elevations precede structural
remodeling (Aim 2). We will determine if spines receiving inputs from specific long-range afferent regions are
selectively targeted (Aim 3). Together, the results are expected to provide insights into the biological basis of
ketamine’s action. As calcium is an essential checkpoint for synaptic plasticity in the frontal cortex, delineating
its role in antidepressant action will accelerate the evaluation of candidate compounds and the development of
more targeted treatments.

## Key facts

- **NIH application ID:** 10048545
- **Project number:** 1R01MH121848-01A1
- **Recipient organization:** YALE UNIVERSITY
- **Principal Investigator:** CHUN-HAY ALEX KWAN
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $567,043
- **Award type:** 1
- **Project period:** 2020-06-10 → 2025-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10048545

## Citation

> US National Institutes of Health, RePORTER application 10048545, A Dendritic Substrate for Fast-Acting Antidepressant Action (1R01MH121848-01A1). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10048545. Licensed CC0.

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