# Single synapse analysis of synaptic plasticity by combining electrophysiology and array tomography

> **NIH NIH R01** · STANFORD UNIVERSITY · 2020 · $565,122

## Abstract

The most well-established mechanism for the expression of the activity-dependent forms of
synaptic plasticity known as long-term potentiation (LTP) and long-term depression (LTD) is the
trafficking of AMPA receptors (AMPARs) into or out of the postsynaptic membrane. This
trafficking is believed to be shaped in important ways by the identity of the particular receptor
subunits present in the dendritic spine. The dominant model of AMPAR trafficking has held that
the unique C-terminal tails of these subunits play an important role in sorting these receptors to
their intended destination, whether it be in the surface membrane, specifically in the
postsynaptic membrane, or at an intracellular site. Recently that model has been partly
challenged by findings that suggest that AMPARs are not sorted by subunit composition, but
rather that the primary driver of LTP induction is a change in the properties of the postsynaptic
density and/or in dendritic spine volume that captures additional AMPARs in a subunit
indiscriminate manner. Yet at the same time, previous data, including our own, strongly support
the idea that specific AMPAR subunits in the postsynaptic membrane are crucial for the
induction of LTP and the specification of defined synaptic plasticity states. This grant seeks to
leverage the existing knowledge about the trafficking of AMPA receptors in a new series of
experiments that combines our established techniques of paired-neuron electrophysiological
recordings with our more recently acquired ability to use array tomography to track the location
of glutamate receptor subunits on dendritic spines of synapses specifically known to have
undergone plasticity. We will test competing hypotheses concerning the nature of AMPA
receptor trafficking into postsynaptic membranes during the induction of synaptic plasticity.

## Key facts

- **NIH application ID:** 9830679
- **Project number:** 5R01MH111768-04
- **Recipient organization:** STANFORD UNIVERSITY
- **Principal Investigator:** Vernon Daniel MADISON
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $565,122
- **Award type:** 5
- **Project period:** 2016-12-23 → 2021-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9830679

## Citation

> US National Institutes of Health, RePORTER application 9830679, Single synapse analysis of synaptic plasticity by combining electrophysiology and array tomography (5R01MH111768-04). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9830679. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*