# Microtubule Dynamics in Neuronal Dendrites

> **NIH NIH R01** · UNIVERSITY OF WISCONSIN-MADISON · 2020 · $362,364

## Abstract

PROJECT SUMMARY/ABSTRACT
A functional nervous system requires both the appropriate development of dendritic spines and their
functional plasticity throughout life. Because dendritic spines are the primary sites of contact with
presynaptic axons in excitatory neurons of hippocampus and cortex, their structure and function have
been studied in great detail. During development, spines undergo marked changes in structure,
progressing from motile filopodial protrusions to stable mushroom-shaped spines. Activity-driven
structural changes in spines of mature neurons also play important roles in learning and memory. It is
therefore not surprising that changes in dendritic spines are one of the first harbingers of neuronal
dysfunction in many developmental diseases, such as Fragile X syndrome and autism, as well as
neurodegenerative diseases, such as Alzheimer's disease. Actin filaments play important roles in the
formation, maintenance and plasticity of dendritic spine structure. Prominent in dendrite shafts,
microtubules (MTs) function as stable railways for intracellular transport, but also exhibit bouts of rapid
polymerization and depolymerization, termed dynamic instability. We discovered that MTs remain
dynamic in dendrites throughout neuronal development and are capable of rapidly polymerizing into and
out of dendritic spines in an activity-dependent fashion. In this proposal we will test the hypothesis that
MT invasion of dendritic spines is a tightly regulated process resulting in motor-driven transport of cargo
directly into and out of dendritic spines. Specifically, we will: 1) Determine the molecular mechanism by
which MTs target specific spines, 2) Identify motor proteins and cargo that are transported into spines
along MTs, and 3) Determine how material is transported out of spines along MTs. This work will provide
fundamental insights into synaptogenesis and synaptic plasticity. Furthermore, because dendritic spines
play essential roles in learning and memory and are the structures affected in numerous psychiatric and
neurological diseases, these studies hold promise for novel cytoskeletal-based therapies for synaptic
dysfunction.

## Key facts

- **NIH application ID:** 9934012
- **Project number:** 5R01NS098372-05
- **Recipient organization:** UNIVERSITY OF WISCONSIN-MADISON
- **Principal Investigator:** Erik W Dent
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $362,364
- **Award type:** 5
- **Project period:** 2016-05-01 → 2022-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9934012

## Citation

> US National Institutes of Health, RePORTER application 9934012, Microtubule Dynamics in Neuronal Dendrites (5R01NS098372-05). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9934012. Licensed CC0.

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