# Brain-wide input and output wiring diagram of oxytocin neurons and its function in claustrum-endopiriform complex

> **NIH NIH R01** · PENNSYLVANIA STATE UNIV HERSHEY MED CTR · 2020 · $464,984

## Abstract

Abstract
Social behavior reflects highly complex, multimodal, internal/external stimuli integration and is critical to the
survival of many animals, including humans. Impaired social behavior has been implicated in many different
mental disorders. Despite its importance, we know relatively little about underlying neural circuit mechanisms
to generate context appropriate social behavioral response. Oxytocin (OT) is a neuropeptide that plays an
essential role in regulating social behavior. Genetic mutations that affect OT signaling have been heavily
implicated in brain disorders with social behavioral impairments such as autism spectrum disorder. OT neurons
predominately located in the hypothalamus receive input from the sensory system and other brain regions to
integrate both external stimuli and internal information. In turn, hypothalamic OT neurons release OT to the
bloodstream via the pituitary to affect body metabolism and provide central projection to other brain regions. To
support OT function, OT receptor (OTR) is highly expressed in socially important brain areas. Particularly, OT
signaling via OTR in different brain regions is known to increase social information processing while
suppressing background noise to achieve circuit specific neural modulation. Despite prominent roles of OT
signaling during social behavior, precise neuroanatomical connectivity and circuit specific effects of OT
signaling remain unclear. Here, we propose to study the detailed anatomical organization of hypothalamic OT
neurons and to investigate its function in a novel mouse brain area. It has been technically challenging to image
and analyze microscopic structures (e.g., axons) throughout the entire mammalian brain. To overcome this
barrier, we previously developed a novel method that combines serial two-photon tomography (STPT) imaging
of whole mouse brains at cellular resolution with viral and genetic tools to achieve quantitative input and output
maps of cell type specific populations. Using this approach, we will examine topographically segregated output
(Aim1) and input (Aim2) maps of hypothalamic OT neurons and will develop web visualization platform to
display high-resolution images for further analysis. Moreover, we will investigate OT signaling function in the
claustrum-endopiriform complex to guide normal social behavior based on our preliminary results (Aim3). We
believe these studies will establish a much-needed detailed anatomical wiring diagram of OT neurons and will
provide a foundation to elucidate the neural circuit basis of mature social behavior in health and disease.

## Key facts

- **NIH application ID:** 9880290
- **Project number:** 5R01MH116176-03
- **Recipient organization:** PENNSYLVANIA STATE UNIV HERSHEY MED CTR
- **Principal Investigator:** Yongsoo Kim
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $464,984
- **Award type:** 5
- **Project period:** 2018-06-01 → 2023-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9880290

## Citation

> US National Institutes of Health, RePORTER application 9880290, Brain-wide input and output wiring diagram of oxytocin neurons and its function in claustrum-endopiriform complex (5R01MH116176-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9880290. Licensed CC0.

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