Brain Circuit Damage Due to Childhood Social Isolation

A research team at the Icahn School of Medicine at Mt. Sinai have identified specific sub-populations of brain cells located in the prefrontal cortex that are required for normal sociability in adulthood and are also profoundly vulnerable to social isolation in juvenile mice. The prefrontal cortex in the brain is a key part of the brain that regulates social behavior. The study conducted on mice shows long lasting effects and also directs the way to potential treatments.

Loneliness and isolation are both recognized as serious threats to mental health. Young people are feeling a growing sense of isolation even as the world becomes increasingly connected through digital platforms. The COVID-19 pandemic which has forced many countries around the world to implement school closures and social distancing, increases the need for better understanding of the mental health consequences of loneliness and social isolation.

Research has shown that social isolation during childhood is detrimental to adult brain function and behaviors across mammalian species. However, the underlying neural circuit mechanisms are poorly understood.

The research team’s discovery sheds light on a previously unrecognized role of the sub-populations of brain cells in the prefrontal cortex. These cells are known as medial prefrontal cortex neurons projecting to the paraventricular thalamus which is the area of the brain that relays signals to various components of the brain’s reward circuitry. If the team’s findings can be replicated in humans, it could lead to treatments for psychiatric disorders that are connected to isolation.

The team also demonstrated that the vulnerable circuit they identified is a promising target for treatments for deficits in social behaviors. By stimulating the specific prefrontal circuit projecting to the thalamic area in adulthood, they were able to rescue sociability deficits caused by social isolation during the juvenile years.

The team found that in male mice two weeks of being socially isolated immediately following weaning led to a failure to activate medial prefrontal cortex neurons projecting to the paraventricular thalamus during social exposure in adulthood. They discovered that juvenile isolation led to not only reduced excitability of the prefrontal neurons projecting to the paraventricular thalamus, but also increased inhibitory input from other related neurons. This suggests that a circuit mechanism underlies sociability deficits caused by juvenile isolation.

In order to determine if acute restoration of the activity of the prefrontal projections to the paraventricular thalamus is sufficient to ameliorate sociability deficits in adult mice that had been put under juvenile social isolation, the researchers employed a technique known as optogenetics to selectively stimulate the projections to the thalamus.

In addition, they used chemogenetics in the study which enabled them to stimulate particular neurons in freely moving animals through pulses of light. Chemogenetics allows non-invasive chemical control over populations of cells.

By employing both techniques, the team was able to quickly increase social interaction in the mice once light pulses or drugs were given to them. The team checked the presence of social behavior deficits just before stimulation and when they checked the behavior while the stimulation was going on, they found that the social behavior deficits were reversed.

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

To view the original scientific study click below

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