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, | Credit: (c) Jorm S / stock.adobe.com] Person and
shadow, loneliness concept (stock image).

Credit: (c) Jorm S / stock.adobe.com [Person and shadow, | Credit:
(c) Jorm S / stock.adobe.com] Person and shadow, loneliness concept
(stock image).

Credit: (c) Jorm S / stock.adobe.com Close 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 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 ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2020/08/200831112345.htm

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