# Saturation of Synaptic Plasticity at Individual Dendritic Spines

> **NIH NIH F99** · UNIVERSITY OF CALIFORNIA AT DAVIS · 2021 · $39,440

## Abstract

Abstract
The ability of organisms to learn is crucial for them to survive and adapt to new environments. Learning relies
on the brain’s capacity to change the connections between neurons to alter circuit functions, or synaptic plasticity.
Dysfunction in the regulation of synaptic plasticity, or ability of the brain to change in response to stimuli, has
been implicated in neurological disorders like Alzheimer’s disease, autism spectrum disorder and drug addiction.
Much of the research on the synaptic plasticity associated with learning has focused on dendritic spines,
membranous protrusions that are the postsynaptic sites of excitatory transmission in the cortex. Notably, learning
in humans is improved when breaks are incorporated into learning sessions, in a process called spaced learning.
Notably, spaced training increases learning in rodent models of Fragile X, Angelman’s and Down syndromes,
which are learning impaired. One idea is that the need for breaks is due to a temporary saturation of plasticity at
the synapses involved in this learning. Indeed, it has been shown that saturation of potentiation leads to
impairment of learning in animal models. After an initial stimulation leads to circuit potentiation, a second stimulus
is unable to produce potentiation unless the intervals between stimuli were increased. However, the mechanisms
that lead to saturation of plasticity remain poorly defined. The goal of this proposal is to determine the cellular
and molecular mechanisms by which this saturation occurs. My current data show that saturation of synaptic
strengthening occurs at individual synapse level and that the saturation occurs via postsynaptic mechanisms.
My data also demonstrate that saturation of synaptic strengthening at individual spines can be overcome by
increased levels of stimulation and that saturation is also release over time as spines stimulated 60 minutes after
their initial stimulation are able to exhibit further synaptic strengthening. Finally, my data show that CaMKII
activity is reduced in spines which are experiencing saturation. Using 2-photon (2p) imaging, 2p glutamate
uncaging, calcium imaging and conditional single cell knock out animals, I propose to rigorously investigate the
molecular and cellular mechanisms that drive saturation of plasticity at individual spines. The results of these
experiments will further our knowledge of synaptic plasticity and its limitations and could elucidate novel drug
targets for the treatment of neurological disorders and learning disabilities. After completing my dissertation, I
intend to pursue a postdoctoral position studying the role of mitochondrial signaling and dysfunction in
neurodegenerative diseases. The proposed experiments and training plan will provide a strong foundation for
my transition to postdoctoral training and will support me in my long-term goal of an academic research position.

## Key facts

- **NIH application ID:** 10393380
- **Project number:** 1F99NS125772-01
- **Recipient organization:** UNIVERSITY OF CALIFORNIA AT DAVIS
- **Principal Investigator:** Juan C Flores
- **Activity code:** F99 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $39,440
- **Award type:** 1
- **Project period:** 2021-09-01 → 2023-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10393380

## Citation

> US National Institutes of Health, RePORTER application 10393380, Saturation of Synaptic Plasticity at Individual Dendritic Spines (1F99NS125772-01). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10393380. Licensed CC0.

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