# Optical methods for imaging and manipulating dendritic spines in vivo

> **NIH NIH R34** · COLUMBIA UNIV NEW YORK MORNINGSIDE · 2020 · $699,980

## Abstract

Dendritic spines cover dendrites of most mammalian neurons and receive almost
all excitatory connections in the cortex. Although their role in these circuits is
therefore likely to be crucial, the function of spines is still poorly understood.
Spines are chemical compartments, and this could provide the biochemical
isolation necessary to implement input-specific synaptic plasticity. But recent
experiments have suggested that, in addition, spines could compartmentalize
voltage. This could have a major impact on excitatory synaptic potentials, altering
them as they are injected into the dendrites. In fact, by regulating the spine neck
dimensions, dendritic spines could rapidly control synaptic strength. While there
is in vitro data supporting this hypothesis, there is currently no direct
measurements of spine voltages in vivo.
Our goal is to build tools to determine if spines indeed have an electrical function
in vivo. We propose two types of optical tools to image and optically manipulate
spines in mouse visual cortex in vivo. In the first aim we will build, calibrate and
test two novel Genetically Encoded Voltage Indicators (GEVIs), which will be
designed for optimal two-photon cross section and for targeting to dendritic
spines. In the second aim, we will pilot the use of simultaneous two-photon
imaging and optogenetics of individual spines in vivo and we will also synthesize
and test a RuBi caged-TTX for two-photon photorelease in vivo.
Our research will develop tools that could enable the systematic study of the
function of dendritic spines and other neuronal nanocompartments. Testing the
electrical function of spines could also help to better understand the
pathophysiology of many mental retardation syndromes, characterized by
abnormally long spines.

## Key facts

- **NIH application ID:** 9978285
- **Project number:** 1R34NS116740-01
- **Recipient organization:** COLUMBIA UNIV NEW YORK MORNINGSIDE
- **Principal Investigator:** Roberto Etchenique
- **Activity code:** R34 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $699,980
- **Award type:** 1
- **Project period:** 2020-04-15 → 2023-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9978285

## Citation

> US National Institutes of Health, RePORTER application 9978285, Optical methods for imaging and manipulating dendritic spines in vivo (1R34NS116740-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9978285. Licensed CC0.

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