Targeting VIP Neuron Cells to Ease Anxiety

“Anxiety is an experience that is familiar to many of us and pathological in too many cases. Can we find what anxiety looks like in the brain? If we can, can we control it?” Vikaas Sohal, MD, PhD

Anxiety fascinates Vikaas Sohal, MD, PhD. 

Of all the neuropsychiatric conditions, anxiety is one we all recognize. In the right doses, anxiety keeps us alive by sending a warning signal to our brain, as in: “A saber-toothed cat is growling outside the cave, stay inside.” or “The light is red, don’t walk.” 

All too often, however, anxiety runs amok. 

“We must have anxiety in our lives. It is an important part of evolution to avoid dangerous situations,” Dr. Sohal notes. “But sometimes, anxiety seems to take on a life of its own and becomes really pathological. I want to understand how our brains function in a normal, optimal range without getting into this pathological range. And when it does, how do we bring it back?”

Winning the Weill Trailblazer Award has given Dr. Sohal the opportunity to figure that out. The award, he says, may make the difference between taking 10 years or more to find the right regulator drugs and identifying effective medication in two to three years. 

“I am a psychiatrist, and I'm also a systems neuroscientist,” he explains. “I am taking basic neuroscience methods and ideas and applying them to difficult clinical problems. This grant is a recognition of that, and I am very grateful.” 

Little is known about anxiety or how drugs prescribed for the condition actually work. Scientists understand that anxiety involves the flow of information across brain circuits and between three different regions of the brain: the hippocampus, prefrontal cortex, and amygdala. 

As a practicing psychiatrist, Dr. Sohal knows the personal cost of anxiety and just how crippling it can be. Almost one-third of all Americans experience either post-traumatic stress disorder, obsessive-compulsive disorder, or Tourette syndrome – all of which have anxiety as a core symptom. Anxiety also is commonly part of a diagnosis of depression, bipolar disorder, schizophrenia, and autism. 

Recently, Dr. Sohal’s lab had a breakthrough when his team discovered cells called vasoactive intestinal peptide (VIP) cells, located in a part of the brain called the prefrontal cortex. These VIP cells may be key to regulating information and – perhaps even more important – the brain’s reaction to that information. He likened the VIP cells to a “knob controlling the volume” from the hippocampus to the prefrontal cortex. 

“In pathological anxiety, it's the inability to turn off that anxiety signal that's a problem,” he says. “It’s very exciting that we have found this cell, the VIP cell, that we think controls the strength of the messages being transmitted.”

Now he is looking for drugs to target and control these cells. “That’s what this project is all about,” he notes. “The Weill award encouraged me to think in a translational direction. We found this one cell type, in spite of all the brain’s complexity, one cell type that seems to have been controlling things – that's really cool, right?” 

UCSF Weill Awards

Susanna Rosi, PhD; and Peter Walter, PhD
John Boscardin, PhD; Andrew Charles, MD; Steve Cummings, MD; and Amy Gelfand, MD