# Role of the Rac1-GEF Tiam1 in Synaptic Plasticity and Hippocampal-Dependent Learning and Memory

> **NIH NIH F31** · BAYLOR COLLEGE OF MEDICINE · 2022 · $46,752

## Abstract

PROJECT SUMMARY
Our ability to learn and form memories relies on the precise and dynamic regulation of excitatory synapses. The
dysfunction of these specialized connections is strongly implicated as a causal factor of cognitive decline. Recent
findings strongly suggest a connection between the gradual impairment of hippocampal synaptic plasticity and
the cognitive decline that accompanies aging and the progression of neurodegenerative diseases. Thus, it is
imperative to further elucidate the mechanisms of hippocampal synaptic plasticity to better understand learning
and memory and to develop effective approaches to treat memory decline. Excitatory synapses are primarily
located on actin-rich protrusions of neuronal dendrites known as dendritic spines. We previously established the
Rac1-specific guanine nucleotide exchange factor (GEF) Tiam1 as an important regulator of spine
morphogenesis that couple’s NMDA-type glutamate receptor (NMDAR) activity to Rac1 signaling in cultured
hippocampal neurons. In both the human and rodent brains, Tiam1 is enriched in the dentate gyrus (DG)
subregion of the hippocampus throughout life. However, its functional role in the mammalian brain, particularly
in adults, is unclear. Our recent preliminary data suggests that Tiam1 plays an ongoing role in regulating synaptic
plasticity within the DG. We found that the deletion of Tiam1 from excitatory neurons in the adult mouse forebrain
enhanced NMDAR-mediated currents in DG granule neurons and synaptic plasticity in the DG. Surprisingly,
Tiam1 null mice also demonstrated enhanced performance in hippocampal-dependent learning and memory.
Based on our preliminary findings, we propose that the Rac1-GEF Tiam1 may serve as an ideal molecular tool
for exploring the mechanisms responsible for maintaining proper synaptic plasticity within the hippocampus as
well as a potential therapeutic target for the treatment of disorders involving memory impairments. Using cutting-
edge techniques that include high-resolution microscopy, viral-mediated activity-dependent neuronal labeling,
molecular and cellular biology, electrophysiology, and behavioral analyses, we propose to determine the role of
Tiam1 in the control of proper synaptic plasticity and cognitive function in the adult brain. Specifically, we propose
to (1) elucidate the mechanisms by which Tiam1 restricts synaptic plasticity and (2) determine Tiam1’s role in
hippocampal-dependent learning and memory. The goals of the proposed study are to reveal key molecular and
cellular mechanisms that limit hippocampal plasticity and learning and memory in the adult brain and help to
identify new therapeutic targets to enhance cognitive function.

## Key facts

- **NIH application ID:** 10403424
- **Project number:** 5F31NS122427-02
- **Recipient organization:** BAYLOR COLLEGE OF MEDICINE
- **Principal Investigator:** Francisco Alejandro Blanco
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $46,752
- **Award type:** 5
- **Project period:** 2021-05-17 → 2024-05-16

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10403424

## Citation

> US National Institutes of Health, RePORTER application 10403424, Role of the Rac1-GEF Tiam1 in Synaptic Plasticity and Hippocampal-Dependent Learning and Memory (5F31NS122427-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10403424. Licensed CC0.

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