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Cells and Circuits: Neurotransmission with a Focus on Dopamine
Over more than a century, neuroscientists have built a framework for studying how the brain works based on the neuron doctrine, which states that nerve cells, or neurons, communicate across a tiny gap, the synapse. Communication, first in the form of an electrical impulse, travels from the body of the sending cell, down a long, slender projection called the axon. At the axon terminal, the electrical signal is transformed into a chemical neurotransmitter, which jumps the synapse and is caught by the receiving cell on short, branching projections called dendrites. Of the many neurotransmitters in the brain, Dr. Deutch and his team focus on the role of dopamine, a neurotransmitter that plays a variety of essential roles in normal brain function and is implicated in a number of neuropsychiatric disorders.
Around the time the neuron doctrine was being worked out, in the late-19th and early-20th centuries, scientists began trying to understand the neuropathology of schizophrenia. But it was not until the latter part of the 20th century that quantitative scientific methods made it possible for them to begin to find some answers. Postmortem studies comparing the brains of healthy subjects with brains of people who had schizophrenia showed that the schizophrenia brain is thinner in an area of the prefrontal cortex, the part of the brain responsible for higher thinking. Experiments with laboratory rats have revealed that the cortex thins when there is loss of dopamine. The cells that respond to dopamine have fewer, shorter dendrites, making it harder for the cells to receive information from messaging cells. These changes are involved in the cognitive deficits in schizophrenia.
The prefrontal cortex connects to various other places in the brain. So the question then becomes, are those changes in dendrites and spines occurring only in cells of a particular circuit? Using a tracer, the researchers found a connection going to the nucleus accumbens, a reward center. In recent years, scientists have begun asking what genes are expressed in these cells that make the cell lose spines or form a circuit or are involved in different symptoms. The goal of this research is to identify genes that serve specific functions and symptoms of mental illnesses. The ultimate aim is to design rational treatments that work better and with fewer side effects than drugs currently available.
Ariel V. Deutch, Ph.D.
Professor of Psychiatry and Pharmacology
Director, National Parkinson Foundation Center of Excellence
Vanderbilt University Medical Center
Brain & Behavior Research Foundation Scientific Council Member
1997 NARSAD Distinguished Investigator Grantee