# Investigation into the synaptic origins of hippocampal replay

> **NIH NIH R00** · UNIVERSITY OF NEW MEXICO HEALTH SCIS CTR · 2021 · $247,449

## Abstract

Project Summary
The aim of this project is to study the synaptic mechanisms that allow particular patterns of neural activity to
become reinstated. In hippocampal circuits, the sequential pattern of neural activity observed during behavior
is later replayed during oscillatory bursts of activity known as sharp-wave ripples (SPW-Rs). Computational
models show that replay could arise due to plasticity of glutamatergic synapses onto excitatory neurons.
However, such excitatory-excitatory connections are weak in hippocampal area CA1, where SPW-R replay is
observed. Therefore, SPW-R replay in CA1 may be inherited from upstream region CA3, which has dense
excitatory recurrents. Alternatively, it is possible that plasticity in inhibitory circuits supports changes in SPW-R
dynamics. This grant will use SPW-R replay to study how neural patterns are learned and recalled.
In the K99 Aims, I will examine whether neural activity is sufficient and synaptic plasticity necessary for
subsequent neural reactivation during SPW-Rs. I will artificially induce patterns of activity in areas CA1 and
CA3 and test whether those patterns are reactivated in the proceeding SPW-Rs and whether reactivation is
restricted to recurrent-dense CA3. Next, I will test for the integrity of SPW-R replay while blocking synaptic
consolidation in CA1 pyramidal cells. Replay disruptions would point to an unexpected role of CA1 plasticity in
defining replay sequences. The R00 portion of the grant focuses on whether replay depends on synaptic
plasticity in inhibitory circuits. First, I will establish whether the synaptic connectivity between CA1 pyramidal
cells and interneurons changes with repetitive pairings in vivo. Next, I will block synaptic consolidation in CA1
GABAergic neurons to assess whether replay is also disrupted. Such a finding would demonstrate a novel role
for plasticity in inhibitory circuits in defining network dynamics. Together, these experiments offer a direct test
of the hypothesis that synaptic plasticity amongst a population of co-active neurons (excitatory and inhibitory)
promotes subsequent reactivation of that population.
To study how synaptic connectivity affects circuit dynamics, this grant combines, for the first time, cell-type
specific control of synaptic consolidation and in vivo electrophysiology. The proposed training will set the
foundation for a career that studies memory on the level of behavior, circuit dynamics, and synaptic function.
The proposed experiments aim to inform clinical use of pharmacology and artificial neural stimulation to aid
learning and recall in people with diseases that cause memory deficits.

## Key facts

- **NIH application ID:** 10264129
- **Project number:** 5R00MH118423-04
- **Recipient organization:** UNIVERSITY OF NEW MEXICO HEALTH SCIS CTR
- **Principal Investigator:** Samuel Arnold McKenzie
- **Activity code:** R00 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $247,449
- **Award type:** 5
- **Project period:** 2018-09-21 → 2023-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10264129

## Citation

> US National Institutes of Health, RePORTER application 10264129, Investigation into the synaptic origins of hippocampal replay (5R00MH118423-04). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10264129. Licensed CC0.

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