# The Dynamic AMPA Receptor Interactome During Plasticity and Learning

> **NIH NIH R37** · JOHNS HOPKINS UNIVERSITY · 2024 · $653,462

## Abstract

Summary
AMPA receptors (AMPARs) are the major excitatory neurotransmitter receptors in the brain and their dynamic
trafficking is essential for synaptic plasticity that underlies memory. AMPARs participate in vast postsynaptic
protein complexes that impact their properties and trafficking. We hypothesize that dynamic rearrangements in
postsynaptic protein-protein interactions (PPIs) tune AMPAR levels in response to stimuli, giving rise to synaptic
plasticity and memory. We previously identified GRIP1/GRIP2, PICK1 and others as key synaptic proteins that
regulate AMPAR trafficking and plasticity through dynamic and selective interactions with the cytoplasmic
domains of the receptor. Recent evidence suggests that AMPARs might also regulated by yet unidentified
interactions with their extracellular N-terminal domain. Advances in proximity-dependent biotinylation with
miniTurbo has recently enabled identification of in vivo protein interactions, occurring both extracellularly and
intracellularly, by quantitative mass spectrometry. This technology has been pioneered to map synapse
composition in vivo, but has never been used to study PPIs or synaptic plasticity in this capacity. We will extend
our characterization of AMPAR trafficking during plasticity in vivo by fusing the genetically encodable biotin
ligase, miniTurbo, to either the extracellular N- or intracellular C-termini of GluA1/2-AMPARs and deliver them
to the hippocampus of mice using viruses. We will then observe how AMPAR PPIs change in two complementary
models of plasticity – the inhibitory avoidance model of rodent memory and its direct electrophysiological
correlate, LTP of the CA3→CA1 synapse. Identification of PPIs that are common to these two models of plasticity
will not only further our model of AMPAR trafficking during plasticity but will also identify common biochemical
processes between LTP and learning and memory. Moreover, synaptic proteins that impact AMPAR trafficking
have recently been associated with various neuropsychiatric disorders such as intellectual disability, autism, and
schizophrenia and thus understanding these processes may have impact on potential therapeutic approaches
to these disorders.

## Key facts

- **NIH application ID:** 10817013
- **Project number:** 5R37NS036715-25
- **Recipient organization:** JOHNS HOPKINS UNIVERSITY
- **Principal Investigator:** Richard L Huganir
- **Activity code:** R37 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $653,462
- **Award type:** 5
- **Project period:** 1997-08-01 → 2026-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10817013

## Citation

> US National Institutes of Health, RePORTER application 10817013, The Dynamic AMPA Receptor Interactome During Plasticity and Learning (5R37NS036715-25). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10817013. Licensed CC0.

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