Discovery Of Brain Circuit Damaged By Social Isolation During Childhood

Loneliness is recognized as a serious threat to mental health, even as the world has become more connected via digital platforms people in our modern society are feeling a growing sense of isolation. With recent events, many countries implemented restrictions such as school, park and playground closures, distancing, and closure of many establishments which has been increasing the feelings of isolation and magnifies the need for a better understanding of the mental health consequences of social isolation and loneliness. 

Previous research has shown that social isolation during childhood in particular is detrimental to adult brain function and behaviour across mammalian species, but the underlying neural circuit mechanisms have remained poorly understood. The researcher’s findings from this study published in Nature Neuroscience describe previously unrecognized roles of medial prefrontal cortex neurons projection to the paraventricular thalamus, which is the brain area that relays signals to various components of the brain’s reward circuitry. Should these findings be replicated in humans it may lead to treatments for psychiatric disorders that are 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, Ph.D., 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."

Male mice that were socially isolated for two weeks after being weaned was found to lead to a failure to activate medial prefrontal cortex neurons projecting to the paraventricular thalamus during social exposure in adulthood. Juvenile isolation led to reduced excitability of the prefrontal neurons projecting to the paraventricular thalamus and increased inhibitory input from other related neurons; which suggests that a circuit mechanism underlying sociability deficits was caused by juvenile social isolation. 

Chemogenetics and optogenetics techniques were selectively used to determine whether acute restoration of the activity of prefrontal projections to the paraventricular thalamus would be sufficient enough to ameliorate sociability deficits in adult mice that were subjected to juvenile social isolation. Chemogentic allows for non-invasive chemical control over cell populations, and optogenetics enables stimulation of particular neurons in freely moving animals with pulses of light; by using these techniques the researchers were able to rapidly increase the social interaction of these mice once the light pulse and drugs were administered. 

"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.

Social behaviour deficits are common to many neurodevelopmental and psychiatric disorders including schizophrenia and autism, the identification of these specific prefrontal neurons may provide therapeutic targets for the improvement of social behaviour deficits that are common across a range of psychiatric disorders. For example, the identified circuits could potentially be modulated using techniques such as transcranial magnetic stimulation and/or transcranial direct current stimulation.