# Investigating reciprocal interactions between circuit and synaptic function

> **NIH NIH R01** · UT SOUTHWESTERN MEDICAL CENTER · 2024 · $402,813

## Abstract

PROJECT SUMMARY/ABSTRACT
 The patterns of connectivity across the neural networks of the brain play a critical role in determining how
those networks function. However, the mechanisms through which the architecture of a circuit supports
information encoding or storage remain unclear. In addition, circuit-level activity patterns drive changes in the
strength of synapses across that circuit, which in turn necessarily alters how the circuit behaves. While
considerable work has elucidated many cellular and molecular components of synaptic plasticity, the precise
reciprocal interaction between in vivo activity patterns, synaptic plasticity, and circuit level function remains
unclear. The brain expresses several distinct types of internally generated sequences of neuronal activity
independent of external sensory stimuli, and such temporally precise, self-organized sequences play a crucial
role in information processing and memory formation/retrieval. Due to their independence from external inputs,
internally generated sequences serve as a powerful model to explore the fundamental relationship between the
connectome and network function. The hippocampus, a brain area critical for the formation of many types of
memory, generates a well-defined type of neuronal sequence, sharp-wave/ripple (SWR)-associated replay,
which is observed during “offline” states such as rest or sleep. The central objectives of this proposal are to
identify the in vivo connectome architecture of the hippocampal network, quantify how these connection
patterns regulate activity across the circuit during active “online” encoding and during “offline” SWR
sequences, measure how in vivo activity patterns across this neural network change the weights of synaptic
connections, and establish how those synaptic changes in turn impact circuit function. Supported by
considerable preliminary data, these ambitious aims will be achieved through a combination of ultra-high
density, large-scale in vivo electrophysiology followed by in-depth computational analysis of the resulting data,
and rapid in vivo optical labeling of active neural populations followed by ex vivo physiological quantification of
synaptic function. In Aim 1, we will directly test two models with differing predictions regarding the impact of
local hippocampal connectivity on place field distribution and activity patterns during SWRs. In Aim 2, we will
test the hypothesis that coordinated activity of synaptically connected neuron pairs during behavior (e.g.,
overlapping place fields) potentiates their synaptic connections, which in turn impacts the content of
subsequent SWRs. In Aim 3, we will directly quantify the synaptic consequences of in vivo activity via whole
cell electrophysiology performed in neurons which were either active or silent in an immediately prior
experience. Together, this study is expected to meaningfully advance our understanding of circuit-level brain
function by revealing the fundamental principles which a...

## Key facts

- **NIH application ID:** 10878114
- **Project number:** 1R01NS137020-01
- **Recipient organization:** UT SOUTHWESTERN MEDICAL CENTER
- **Principal Investigator:** BRAD E PFEIFFER
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $402,813
- **Award type:** 1
- **Project period:** 2024-09-15 → 2029-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10878114

## Citation

> US National Institutes of Health, RePORTER application 10878114, Investigating reciprocal interactions between circuit and synaptic function (1R01NS137020-01). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10878114. Licensed CC0.

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