# Synaptic plasticity across the lifespan

> **NIH NIH R01** · UNIVERSITY OF TEXAS AT AUSTIN · 2021 · $565,538

## Abstract

The overall goal is to understand synaptic mechanisms of learning and memory. Long-term potentiation (LTP)
is a model of learning and memory that is well-suited to investigate these processes. Dendritic spines host about
ninety percent of excitatory synapses in the brain and are well known to show structural plasticity following
induction of LTP. The developmental onset of dendritic spines coincides with an abrupt developmental onset for
LTP lasting more than three hours (L-LTP) at postnatal day 12 (P12) in rat hippocampus. At P10 and P15, LTP
enhances synaptogenesis and small spine formation. With maturation, the LTP-accelerated synaptogenesis
shifts to a process that enlarges specific synapses and retains spine clusters locally but is balanced by reduction
in spine numbers elsewhere on the dendrite. The spine clusters are locally delimited by the availability of smooth
endoplasmic reticulum (SER), an organelle critical for regulating calcium, and the transport of lipids and proteins,
and by the presence of polyribosomes, which mediate local protein synthesis. The LTP-produced synapse
enlargement is greatest on spines that contain a spine apparatus, which is a structure derived from SER that
provides synthesis and post-translational modification of transmembrane proteins. Structural changes in
presynaptic axons are also developmentally regulated following LTP and mirror the spine changes with new
boutons forming to accommodate the LTP-accelerated synaptogenesis at P15, and fewer boutons occurring with
spine reduction at P60. Thus, LTP in developing hippocampus accelerates synaptogenesis, whereas resource-dependent synapse growth and spine clustering occur on mature dendrites. This homeostatic balance in synaptic
plasticity is hypothesized to be disrupted with cognitive decline in the aging brain. A comprehensive analysis of
structural synaptic plasticity during maturation and senescence is proposed as a foundation for understanding
lifelong changes in cognitive capacity. Specifically, the aims are: Aim 1: Evaluate the maturation of resource-dependent synaptic growth and clustering. Aim 2: Determine circuit generality and synapse specificity of
resource-dependent growth and clustering. Aim 3: Determine synaptic foundation of cognitive capacity and
decline in the aging hippocampus. Aim 4: Test importance of the spine apparatus in synapse growth and
clustering. Outcomes promise essential insight into the synaptic basis of learning and memory across lifespan
and will provide basic knowledge that could inform new therapies for developmental and age-related brain
disorders.

## Key facts

- **NIH application ID:** 10192834
- **Project number:** 5R01MH095980-07
- **Recipient organization:** UNIVERSITY OF TEXAS AT AUSTIN
- **Principal Investigator:** KRISTEN M HARRIS
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $565,538
- **Award type:** 5
- **Project period:** 2012-07-09 → 2024-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10192834

## Citation

> US National Institutes of Health, RePORTER application 10192834, Synaptic plasticity across the lifespan (5R01MH095980-07). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10192834. Licensed CC0.

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