Research Updates

Understanding the Brain Abnormalities Behind Schizophrenia and Autism

Vikaas Sohal, M.D., Ph.D., Staglin Family-IMHRO Assistant Professor of Psychiatry at UCSF, has made groundbreaking progress in the realm of mental health. By diligently researching abnormal patterns of activity in the brain’s cerebral cortex, Dr. Sohal’s lab has found specific neuron abnormalities that correlate with schizophrenia symptoms. In addition, Sohal’s team has identified specific neuromodulators that work defectively in mice modeling autism. These encouraging discoveries could unearth potential therapeutic avenues that would impact millions struggling with these disorders worldwide.

Vikaas Sohal and his team have identified a unique class of inhibitory (GABAergic) neurons in the cerebral cortex. In the past, it was believed that inhibitory neurons in the cerebral cortex only transmitted signals over short distances; however, these GABAergic neurons are able to send messages over long distances. Sohal believes that “these long-range projecting GABAergic neurons may play key roles in ‘top-down control’ which is important for higher cognitive functions”. Psychiatric illness is often connected with deficiencies in executive function (i.e., self-governance) and further investigation of these inhibitory neurons could generate a deeper understanding of and potential new treatments for these deficits.

By studying mutant mice with abnormal GABAergic neuron development, Dr. Sohal has discovered a key link between gamma oscillations generated by inhibitory neurons and cognitive deficits associated with schizophrenia. Mice with irregular gamma oscillations showed difficulty performing a rule switching task. When the gamma oscillations were restored using optogenetics, the mice were able to succeed at the rule switching task. Sohal tells us that “these benefits were long-lasting ¬ the improvements in rule switching outlasted the optogenetic stimulation, suggesting that enhancing gamma oscillations in the human brain might accelerate cognitive remediation for individuals with schizophrenia”.

Dr. Sohal’s lab has also made key discoveries pertaining to autism spectrum disorders and the attention deficits associated with autism. By making movies of calcium signals passed between neurons in the prefrontal cortex, Vikaas Sohal has shown that in a normal brain, the neuromodulator acetylcholine desynchronizes activity in different neurons, which is important for attention. When observing different mouse brains modeling autism, these models all show a defect in acetylcholine desynchronization of brain activity. Sohal tells us that “restoring this desynchronization may improve attention in individuals with autism”.

On the strength of his One Mind-funded research, Dr. Sohal’s lab has earned a collaborative grant from the President’s BRAIN Initiative, which will enable him and his colleagues to further investigate, as he says, “patterns of activity in the human brain that are associated with illnesses including depression, anxiety, and chronic pain, and to find new forms of brain stimulation that both alleviate symptoms of these illnesses, and enable the brain to unlearn the harmful patterns of activity associated with these illnesses.” This grant is only one among many that Dr. Sohal has acquired; his lab has also received funding from the National Institute of Mental Health.  One Mind donors should be thrilled to know that their funding has not only already resulted in uniquely powerful discoveries but that their investment in this neuroscience has been compounded by these follow-on grants.

All of us at One Mind are proud that our donors have enabled us to fund this incredible scientist.

Would you like to support research like Dr. Sohal’s? We invite you to donate or to learn how to get involved today.