# Mechanistic study of the role of autism spectrum disorder risk genes in hippocampal CA1 population dynamics during learning and memory

> **NIH NIH F31** · BOSTON UNIVERSITY (CHARLES RIVER CAMPUS) · 2021 · $37,218

## Abstract

PROJECT SUMMARY/ABSTRACT
The hippocampus is a critical brain region for various types of learning and memory, and one powerful paradigm
to investigate hippocampal function in associative learning is trace eye-blink conditioning and extinction learning.
In trace eye-blink conditioning, subjects are presented with a neutral conditioned stimulus (CS), such as tone,
followed by a silent trace interval, followed by an aversive unconditioned stimulus (US), such as a gentle puff of
air to the eye. The subject learns to associate the CS and US, generating a conditioned eye-blink response to
the CS. Extinction learning is probed by removing the US, such that the CS is no longer predictive of the US,
and the subject learns to extinguish the eye-blink response. The behavioral responses to trace conditioning and
extinction learning have been well-documented, but it is unclear how ongoing, real-time activities of hippocampal
neurons contribute to the learning process. Additionally, impaired extinction learning has recently been observed
in patients with psychiatric disorders such as post-traumatic stress disorder (PTSD), generalized anxiety, and
autism spectrum disorder (ASD). The goal of this proposal is to understand how hippocampal neural dynamics
participate in associative learning, assessed by trace conditioning and extinction learning in both healthy and
pathological conditions, by utilizing single-cell resolution calcium and voltage imaging techniques in the CA1 of
the hippocampus while mice perform these behavioral tasks. Using calcium imaging, we recently completed
population analysis of CA1 neurons while wild-type mice perform a trace eye-blink conditioning and extinction
learning task. Additionally, several studies have demonstrated that both human patients with ASD and rodent
models of ASD can acquire trace conditioning similarly to controls, but they are impaired in extinction learning;
they continue to respond to the CS even after it is non-predictive of the US. Thus, to probe the hippocampal
network responses underlying intact trace conditioning but impaired extinction learning, we will first perform
calcium imaging in a mouse model of ASD (Aim 1). To examine correlation between hippocampal neuron pairs’
activity during these tasks, we will perform voltage imaging in CA1 neurons with a novel genetically-encoded
voltage sensor, SomArchon, that can reliably measure multiple individual neurons with single-spike, single-cell
resolution in awake, behaving mice (Aim 2). Finally, deficits in excitatory/inhibitory balance are thought to
underlie ASD phenotype. To investigate this hypothesis (via assessing correlation between hippocampal neuron
pairs), we will perform voltage imaging in the same mouse model of ASD utilized in Aim 1 (Aim 3). At the
conclusion of this study, we hope to better understand not only how hippocampal population dynamics
contribute to learning and memory in a healthy condition, but also how these hippocampal responses
are altere...

## Key facts

- **NIH application ID:** 10141811
- **Project number:** 1F31MH123008-01A1
- **Recipient organization:** BOSTON UNIVERSITY (CHARLES RIVER CAMPUS)
- **Principal Investigator:** Rebecca Mount
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $37,218
- **Award type:** 1
- **Project period:** 2021-01-01 → 2023-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10141811

## Citation

> US National Institutes of Health, RePORTER application 10141811, Mechanistic study of the role of autism spectrum disorder risk genes in hippocampal CA1 population dynamics during learning and memory (1F31MH123008-01A1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10141811. Licensed CC0.

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