# The role of glutamatergic inputs to the paraventricular nucleus of the hypothalamus in social behavior and oxytocin neural activity

> **NIH NIH F31** · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · 2022 · $45,152

## Abstract

Project Summary
Oxytocin is a neuropeptide hormone produced in the paraventricular (PVN) and supraoptic nuclei of the
hypothalamus that is implicated in physiological processes such as birth and lactation, as well as in the
expression of social behaviors. To date, many studies have linked brain oxytocin with particular social behaviors,
yet the neural pathways by which external social information is primarily conveyed to oxytocin neurons to
modulate their neural activity and regulate social behavior have been understudied. My preliminary data indicates
that many brain regions implicated in sensory processing and social behavior send monosynaptic inputs to the
PVN, including the posterior intralaminar (PIL) complex of the thalamus. I further show that many PIL-PVN
projections are glutamatergic, that the PIL inputs directly onto oxytocin cells specifically, and that the PIL is
activated during social interaction. Previous studies have shown that glutamate regulates oxytocin neural activity
in vivo in lactating female rodents and in vitro in slices obtained from adult males and neonates. However, the
functional relevance of glutamate-oxytocin circuits in social behavior remains unknown.
Emerging research indicates that dysfunction in glutamatergic signaling leads to impairments in synaptic
transmission causing deficits in social behavior, which is a core symptom of autism spectrum disorder.
Additionally, many of the identified risk genes for autism spectrum disorder are key components of glutamatergic
synapses, including SHANK3. Therefore, I hypothesize that glutamatergic inputs to the PVN, especially those
originating from brain regions that are implicated in the processing of social stimuli, are essential for regulating
the activity of oxytocin neurons during social behavior and that Shank3 mutations disturb this activity. In this
proposal, I will address my hypothesis by characterizing the identity of inputs to oxytocin neurons in the PVN
and manipulating them, using viral and chemogenetic tools, to assess their role in social behavior. I will also use
Miniscope technology to perform in vivo calcium imaging of oxytocin neurons to capture neural activity during
social behavior in freely moving wild-type and Shank3-deficient mice. Furthermore, using this technology in
combination with chemogenetic tools, I will dissect the contribution of specific glutamatergic-PVN circuits in
modulating the activity of oxytocin neurons. This study will provide knowledge about the functional role of
glutamatergic inputs to the PVN in regulating social behavior and oxytocin neural activity. Additionally, this study
will examine the specific effect of Shank3 mutations on the oxytocin system, which could inform potential targets
for treatment.

## Key facts

- **NIH application ID:** 10383996
- **Project number:** 1F31MH129025-01
- **Recipient organization:** ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
- **Principal Investigator:** Amanda Leithead
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $45,152
- **Award type:** 1
- **Project period:** 2022-01-20 → 2025-01-19

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10383996

## Citation

> US National Institutes of Health, RePORTER application 10383996, The role of glutamatergic inputs to the paraventricular nucleus of the hypothalamus in social behavior and oxytocin neural activity (1F31MH129025-01). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/10383996. Licensed CC0.

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