# Postnatal Oxytocin Treatment and Cognitive Function in Fragile X

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA-IRVINE · 2021 · $476,046

## Abstract

Autism Spectrum Disorder (ASD) is a prevalent and heterogeneous neurodevelopmental disorder with high co-
morbidity for intellectual disability. This includes difficulties forming episodic, personal narrative, memories that
are critical for orderly thinking and organizing future behaviors. Episodic memory deficits are thus thought to be
major contributors to cognitive difficulties associated with autism. Many brain changes underlying abnormalities
in ASD appear in childhood suggesting the possibility for effective therapeutic strategies targeting brain
maturation. One candidate therapeutic is the hypothalamic peptide Oxytocin (OXT). Postnatal OXT treatment
improves social behavior in animal models of ASDs and recent work indicates that treatment in childhood
improves social interactions in autistic individuals. OXT acutely facilitates forms of synaptic plasticity, but there
has been little experimental consideration of possible enduring effects of postnatal OXT treatment on learning
and no analyses of effects on episodic memory. We examined this possibility using intranasal OXT (iOXT)
treatment in the Fmr1 KO mouse model of Fragile X Syndrome, and novel paradigms for analyses of `What,
When and Where' encoding. Our preliminary results show that in Fmr1 KOs iOXT treatments during the
second postnatal week (P7-13) fully rescue hippocampal field CA1 long-term potentiation, object location
memory, object identity (What) learning, and social recognition as assessed in adulthood (i.e., >40d after the
last treatment). These findings raise the exciting possibility that a limited period of early life OXT treatment can
effect a life-long rescue of a critical element of cognitive function in ASD. They also raise questions as to the
breadth of effects iOXT has on behavior and the mechanisms involved; these questions will be addressed in
the proposed studies. Aim 1 studies will test if postnatal iOXT treatment of male and female Fmr1 KO mice
rescues encoding for the three major components of episodic memory, social recognition and stereotypic
behavior as assessed in adulthood, and if effects depend on native OXT efflux. We will also determine if there
is a critical period for enduring iOXT effects on behavior. Aim 2 will use electrophysiological recordings of
evoked responses and network activity, analyses of synaptic proteins and signaling, and measures of neuronal
arbors to test if postnatal iOXT treatment normalizes neurobiological processes in the distinct hippocampal
subdivisions related to episodic memory encoding. Finally, Aim 3 will test the hypothesis that early life iOXT
leads to activation of synaptic trophic factor receptors (EGFR, TrkB) in hippocampus, thereby suggesting a
direct route for OXT effects on maturational changes in the structure. Overall, the proposed studies will greatly
expand our current knowledge of OXT actions in the young brain, including potentially critical roles in
regulating hippocampal development and synaptic function. Mo...

## Key facts

- **NIH application ID:** 10233703
- **Project number:** 1R01HD101642-01A1
- **Recipient organization:** UNIVERSITY OF CALIFORNIA-IRVINE
- **Principal Investigator:** Christine M Gall
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $476,046
- **Award type:** 1
- **Project period:** 2021-04-05 → 2026-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10233703

## Citation

> US National Institutes of Health, RePORTER application 10233703, Postnatal Oxytocin Treatment and Cognitive Function in Fragile X (1R01HD101642-01A1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10233703. Licensed CC0.

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