Transgenic Psychomodulation

Grant Type
Grant Year
Institution Location
Institution Organization Name
University of Minnesota
Investigators Name
Burton, Frank, PhD

The brain, like a computer, is a vast collection of distinct types of circuits, defined by different neuron subtypes. And yet, oddly enough, we have never performed detailed circuit-testing of the brain and its epiphenomenon, the mind. In spite of the certainty that neurological and mental conditions are caused by abnormal functioning of brain circuits, we do not even know what most of these circuits do in normal behavior, let alone in brain malfunction. Traditional drugs were first developed to attempt to therapeutically modulate different brain circuits. But these drugs often cause unfortunate and confusing side effects caused by those drugs’ non-specific action upon more than one brain circuit. We are developing the use of recombinant DNA as an ultra-specific drug. In principle, these transferred DNA genes, or “transgenes,” can act on neural circuits much more specifically than traditional drugs. This is because transgenes can be selectively combined with any one of thousands of DNA elements called “pro-moters” that determine the precise cell type in which a gene will be “turned on.” If such transgenes are also designed to adjust the level of neurotransmission in brain circuits (just like a “dimmer switch” adjusts a room light), then for the first time these transgenes will allow us to be able to perform detailed “circuit-testing” of the brain and behavior. In recent research (called transgenic pharmacology), we have designed a neuromodulatory transgene that is being used to perform circuit-testing of dopamine-regulated behavior. Dopamine regulation of behavior is thought to be abnormal in several disorders including Tourette Syndrome (TS) and Obsessive-Compulsive Disorder (OCD). As a first step toward psychomodulatory gene therapy, we are now investigating the ability of our transgenes to restore neurological functions lost in parkinsonism and to suppress drug-induced compulsive behavior. By virtue of our transgene’s ability to induce common signaling pathways in neurons that lead to increased neurotransmission, we are able to selectively activate any desired brain circuit. When a specific transgene was introduced into mice, it caused the mice to exhibit repetitive and compulsive behaviors strikingly reminiscent of those exhibited in humans with TS and OCD. Our data suggest the D1-selective drugs should be investigated for their potential to treat compulsive disorders. Frank H. Burton, Ph.D. University of Minnesota Minneapolis, MN Award: $36,600 Tourette Association of America Inc. – Research Grant Award 1997