Researchers discover a specific brain circuit damaged by social isolation ... https://www.sciencedaily.com/releases/2020/08/200831112345.

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Researchers discover a specific brain circuit damaged by social

isolation during childhood
Study in mice shows long-lasting effects and points the way to potential treatments

Date: August 31, 2020

Source: The Mount Sinai Hospital / Mount Sinai School of Medicine

Summary: Researchers have identified specific sub-populations of brain cells in the prefrontal cortex, a key
part of the brain that regulates social behavior, that are required for normal sociability in adulthood
and are profoundly vulnerable to juvenile social isolation in mice.

FULL STORY

Person and shadow, loneliness concept (stock image).

Credit: © Jorm S / stock.adobe.com

Loneliness is recognized as a serious threat to mental health. Even as our world

becomes increasingly connected over digital platforms, young people in our society are
feeling a growing sense of isolation. The COVID-19 pandemic, which forced many
countries to implement social distancing and school closures, magnifies the need for
understanding the mental health consequences of social isolation and loneliness. While
research has shown that social isolation during childhood, in particular, is detrimental to
adult brain function and behavior across mammalian species, the underlying neural
circuit mechanisms have remained poorly understood.

A research team from the Icahn School of Medicine at Mount Sinai has now identified specific sub-populations of
brain cells in the prefrontal cortex, a key part of the brain that regulates social behavior, that are required for
normal sociability in adulthood and are profoundly vulnerable to juvenile social isolation in mice. The study
findings, which appear in the August 31 issue of Nature Neuroscience, shed light on a previously unrecognized
role of these cells, known as medial prefrontal cortex neurons projecting to the paraventricular thalamus, the brain
area that relays signals to various components of the brain's reward circuitry. If the finding is replicated in
humans, it could lead to treatments for psychiatric disorders connected to isolation.

"In addition to identifying this specific circuit in the prefrontal cortex that is particularly vulnerable to social isolation

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Researchers discover a specific brain circuit damaged by social isolation ... https://www.sciencedaily.com/releases/2020/08/200831112345.htm

during childhood, we also demonstrated that the vulnerable circuit we identified is a promising target for
treatments of social behavior deficits," says Hirofumi Morishita, MD, PhD, Associate Professor of Psychiatry,
Neuroscience, and Ophthalmology at the Icahn School of Medicine at Mount Sinai, a faculty member of The
Friedman Brain Institute and the Mindich Child Health and Development Institute, and senior author of the paper.
"Through stimulation of the specific prefrontal circuit projecting to the thalamic area in adulthood, we were able to
rescue the sociability deficits caused by juvenile social isolation."

Specifically, the team found that, in male mice, two weeks of social isolation immediately following weaning leads
to a failure to activate medial prefrontal cortex neurons projecting to the paraventricular thalamus during social
exposure in adulthood. Researchers found that juvenile isolation led to both reduced excitability of the prefrontal
neurons projecting to the paraventricular thalamus and increased inhibitory input from other related neurons,
suggesting a circuit mechanism underlying sociability deficits caused by juvenile social isolation. To determine
whether acute restoration of the activity of prefrontal projections to the paraventricular thalamus is sufficient to
ameliorate sociability deficits in adult mice that underwent juvenile social isolation, the team employed a
technique known as optogenetics to selectively stimulate the prefrontal projections to paraventricular thalamus.
The researchers also used chemogenetics in their study. While optogenetics enables researchers to stimulate
particular neurons in freely moving animals with pulses of light, chemogenetics allows non-invasive chemical
control over cell populations. By employing both of these techniques, the researchers were able to quickly
increase social interaction in these mice once light pulses or drugs were administered to them.

"We checked the presence of social behavior deficits just prior to stimulation and when we checked the behavior
while the stimulation was ongoing, we found that the social behavior deficits were reversed," said Dr. Morishita.

Given that social behavior deficits are a common dimension of many neurodevelopmental and psychiatric
disorders, such as autism and schizophrenia, identification of these specific prefrontal neurons will point toward
therapeutic targets for the improvement of social behavior deficits shared across a range of psychiatric disorders.
The circuits identified in this study could potentially be modulated using techniques like transcranial magnetic
stimulation and/or transcranial direct current stimulation.

This work was supported by grants from the National Institutes of Health and the National Institute of Mental
Health and The Simons Foundation.

Story Source:

Materials provided by The Mount Sinai Hospital / Mount Sinai School of Medicine. Note: Content may be
edited for style and length.

Journal Reference:

1. Kazuhiko Yamamuro, Lucy K. Bicks, Michael B. Leventhal, Daisuke Kato, Susanna Im, Meghan E. Flanigan,
Yury Garkun, Kevin J. Norman, Keaven Caro, Masato Sadahiro, Klas Kullander, Schahram Akbarian, Scott J.
Russo, Hirofumi Morishita. A prefrontal–paraventricular thalamus circuit requires juvenile social
experience to regulate adult sociability in mice. Nature Neuroscience, Aug. 31, 2020; DOI:
10.1038/s41593-020-0695-6

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The Mount Sinai Hospital / Mount Sinai School of Medicine. "Researchers discover a specific brain circuit
damaged by social isolation during childhood: Study in mice shows long-lasting effects and points the way to
potential treatments." ScienceDaily. ScienceDaily, 31 August 2020. <www.sciencedaily.com/releases/2020/08
/200831112345.htm>.

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