# Building Synaptic Cytoskeleton

> **NIH NIH R01** · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · 2020 · $475,286

## Abstract

The actin cytoskeleton anchors synapse adhesion molecules and generates the flexible architecture that
characterizes dendritic spine shape. It regulates and supports membrane traffic and defines synapse
compartments. It also drives the generation of new synapses and lasting changes in synapse size and shape
that occur in response to salient stimuli. These are long-standing, widely accepted facts. The broad
acceptance of these facts makes it all the more surprising that relatively little is known about how synaptic actin
is generated. What drives its assembly when new synapses are forming, and how does this process differ from
the reorganization that drives spine expansion or shrinkage? This gap in knowledge limits the understanding of
Alzheimer's Disease and related dementias where synapse loss and changes in spine shape are well
documented. It also impacts brain disorders and pathologies, including amyotrophic lateral sclerosis,
schizophrenia, intellectual disability and autism, that can be seeded in the mutation, loss, or gain of actin
regulatory function, and disorders that involve derailed mechanisms of synapse plasticity such as drug
addiction. This gap in knowledge is not an oversight or due to lack of interest. It exists because synapses are
small and difficult to study, actin filaments are exceptionally thin, fragile and dynamic, and several molecular
components important for nucleating actin have only recently been identified. The purpose of this proposal is to
identify the principal actin nucleators relevant to the generation of synapses, and to assess the time, place, and
context in which they act. Not knowing the relevant players is a rate limiting step in the field and the proposed
experiments are a first step toward identifying the nature and location of actin scaffolds relevant to particular
stages of synapse formation, biological actions (e.g. adhesion or trafficking) or to changes in state (e.g.
potentiation or depression).

## Key facts

- **NIH application ID:** 10072429
- **Project number:** 1R01NS115469-01A1
- **Recipient organization:** ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
- **Principal Investigator:** Deanna L Benson
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $475,286
- **Award type:** 1
- **Project period:** 2020-09-01 → 2024-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10072429

## Citation

> US National Institutes of Health, RePORTER application 10072429, Building Synaptic Cytoskeleton (1R01NS115469-01A1). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10072429. Licensed CC0.

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