# Exploring neural circuit mechanisms of social contact and social isolation

> **NIH NIH R01** · SALK INSTITUTE FOR BIOLOGICAL STUDIES · 2021 · $483,871

## Abstract

Humans possess a fundamental need for social contact, which is essential for survival and mental well-
being. Therefore, situations of social isolation, exclusion, or disconnection are highly aversive, and can lead to
negative feelings of loneliness. However, we have a poor understanding of the brain circuitry which underlies
this emotional state, and how this generates a need to seek social contact. Additionally, in many
neuropsychiatric disorders, including depression, anxiety, and autism spectrum disorders social withdrawal and
impaired social interaction are defining features. As a first step, we must uncover the neural mechanisms
which underlie our inherent drive to seek and engage in social contact, in order to understand how these might
go awry in mood disorders.
We have recently gathered exciting preliminary data implicating an understudied population of
dopamine (DA) neurons in the dorsal raphe nucleus (DRN) in representing the subjective experience of social
isolation. We find that these neurons are sensitive to acute periods of social isolation, and manipulations of
their activity in vivo can induce or suppress a ‘loneliness-like’ state, in a manner predicted by social rank. We
hypothesize that the DRN DA neurons mediate a ‘loneliness-like’ state, and provide the motivational drive to
re-establish social contact. With this research proposal, we therefore seek to explore and unravel this largely
uncharted territory within the dopaminergic circuit and explore its functional importance for social contact.
To achieve this, we will first identify the input-output architecture of this type of neurons. This will
generate a neuroanatomical roadmap and the foundation for detailed circuit- and projection-specific analyses.
Furthermore, we will test which input and output regions are involved in conveying essential information about
the social environment. For this we will examine the naturally-occurring activity within the DRN dopamine
neurons, and establish how manipulating their activity affects social behavior. This will provide insight into how
the neural dynamics of this population differ in grouped and socially-isolated animals. We will additionally
explore the DRN DA system in relation to the establishment and maintenance of social hierarchy. These
experiments will unravel the relationship between DRN DA function and social rank, and further our
understanding of the neural mechanisms which contribute to individual differences in social behavior.
Importantly, we will work with Ian Wickersham and Liqun Luo to be at the forefront of viral vector
approaches needed to successfully execute this proposal. Given my lab’s track record, the unique preliminary
data set generated by my team, the questions identified and the necessary steps already taken, we are
particularly well-suited to execute this study, and are thrilled to drive the field of social neuroscience forward.

## Key facts

- **NIH application ID:** 10159755
- **Project number:** 5R01MH115920-04
- **Recipient organization:** SALK INSTITUTE FOR BIOLOGICAL STUDIES
- **Principal Investigator:** Kay Maxine Tye
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $483,871
- **Award type:** 5
- **Project period:** 2019-04-01 → 2023-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10159755

## Citation

> US National Institutes of Health, RePORTER application 10159755, Exploring neural circuit mechanisms of social contact and social isolation (5R01MH115920-04). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10159755. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*