# High throughput molecular screen for environmental epigenetic modifiers in brain development and ASD

> **NIH NIH K00** · UNIVERSITY OF CALIFORNIA LOS ANGELES · 2021 · $84,750

## Abstract

Oxytocin is a peptide and hormone known to be involved in myriad social behaviors. Dysfunction of
the oxytocinergic signaling has also been implicated in the etiology of social deficits and
neuropsychiatric disease. The mechanisms of oxytocin signaling in the brain, however, are
incompletely understood. In this proposal, we dissect oxytocinergic signaling in the hippocampal
subregion CA2, which is known to be a locus of oxytocin signaling and has, itself, been implicated in
social behavior. Aim 1 of the proposal describes our lab's recent work elucidating the mechanism of
oxytocin-driven excitation in hippocampal neurons. Activation of the oxytocin receptor (OXTR)
depolarizes CA2 pyramidal cells by activation of a Gq-coupled signaling pathway that ultimately
inhibits a potassium current known the M-current, or IM. Described most thoroughly in CA2 pyramidal
cells, this mechanism appears to generalize to interneurons in CA1 and CA2. Joint regulation of
excitatory and inhibitory neurons in CA2 shapes the propagation of activity from CA2 to its primary
downstream target CA1. In addition to excitation, OXTR stimulation can cause hyperpolarization of
hippocampal neurons. Experiments described in Aim 2 deconstruct the two opposing mechanisms
downstream of the OXTR, with particular emphasis on how they produce the complex dynamics
recorded in vitro. Moreover, we build upon the observation that there at least two subpopulations of
CA2 pyramidal cells, only one of which expresses the OXTR. We propose experiments to compare
the inputs, outputs and intrinsic properties of these two subpopulations. Aim 2 concludes with
behavioral experiments driven by the hypothesis that oxytocin is necessary for CA2-mediated social
behavior. Aim 3 describes work to be completed in the postdoctoral training period, using
ethologically relevant behaviors to drive in vitro mechanistic studies. In vivo recordings will bridge
biophysical and behavioral observations. This methodology will be applied to the investigation of
social behaviors, with particular emphasis on how neural dynamics are modulated.

## Key facts

- **NIH application ID:** 10160907
- **Project number:** 5K00ES032608-04
- **Recipient organization:** UNIVERSITY OF CALIFORNIA LOS ANGELES
- **Principal Investigator:** Katherine Eyring
- **Activity code:** K00 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $84,750
- **Award type:** 5
- **Project period:** 2018-07-01 → 2024-02-29

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10160907

## Citation

> US National Institutes of Health, RePORTER application 10160907, High throughput molecular screen for environmental epigenetic modifiers in brain development and ASD (5K00ES032608-04). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10160907. Licensed CC0.

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