Research Probes Basal Ganglia to Uncover Neural Signaling Patterns and What Goes Wrong in Parkinson's and Other Disorders
In the world of the brain, the basal ganglia are the teachers who hand out the rewards and punishment that allow us to learn from consequences. They also are at the root of a wide range of disorders, including Parkinson’s, depression and the formation of addictive behaviors.
Once considered a rather primitive part of the brain mainly involved in voluntary motor control, the basal ganglia in recent years have been found to be part of a complex learning system that alerts the rest of the brain to what is rewarding and what is not. Uncovering the inner workings of the basal ganglia, James M. Tepper, distinguished professor of neuroscience, is focused on revealing the patterns of their neural circuitry that signal other parts of the brain. Within the basal ganglia, he explains, it’s not merely the rate at which those neurons fire but rather the pattern of signaling that is central to their functioning properly. That if a pattern, for example, of da, da, ta is somehow switched to dee, dee, ta, the basal ganglia’s reward and punishment signals break down.
The basal ganglia are a group of nuclei situated at the base of the brain that communicate with the frontal cortex, thalamus and other areas. Along with controlling motor function, they regulate reward-feedback learning and behavior by transmitting a spike in dopamine – a reward – or a decrease in that transmission – a punishment.
In Parkinson’s, it is the death of dopamine neurons that results in movement disorders. The absence of those neurons deprives the brain of dopamine also resulting in cognitive deficits, depression and behavioral issues in that disease and other disorders.
"In Parkinson's no one knows yet why dopamine neurons die, but we’re almost certain it is because the neurons are not receiving the proper signals," says Tepper. "By figuring out the circuitry that controls the patterns of firing that causes dopamine neurons to do their reward dance, we might be able to correct a system that has gone array."
More than just signaling what is and is not rewarding, the basal ganglia communicate the value and degree of an experience, transmitting whether it is mildly rewarding, highly rewarding, tremendously rewarding or not rewarding at all. When dopamine cells die, those with Parkinson’s and similar disorders lose their ability to learn from reward while their ability to learn from negative feedback also decreases. The loss of that ability to perceive the rewarding aspects of life may be part of what leads to depression. Conversely, addictive behaviors can develop through reward signals that are continually strengthened by repetition.
Working under a grant from the CHDI Foundation, Tepper also is seeking to uncover the changes that occur in the basal ganglia’s signaling patterns in Huntington’s disease. While the gene for Huntington’s has been identified, a cure has yet to be developed. As also may be the case in Parkinson’s, explains Tepper, the root cause may be that the firing pattern in the basal ganglia has been disrupted. “It may be that another wave has taken over and become so strong that it prevents meaningful information from getting through. If we can uncover what is happening deeper down in the system, then it also may become possible to develop interventions.”
James M. Tepper earned his B.A. in psychology, and his M.A. and Ph.D. in biological psychology from the University of Colorado, Boulder. He performed his post-doctoral research at the University of California, San Diego, where he focused his work on the structure and function of the basal ganglia. He joined the Center for Molecular and Behavioral Neuroscience in 1987 as the first faculty member hired by Co-Directors Ian Creese and Paula Tallal, and in 2008 was appointed a distinguished professor by the Rutgers Board of Governors. He is a fellow of the prestigious American Association for the Advancement of Science and president of the International Basal Ganglia Society. He also is a skilled guitarist who has produced two CDs.
- GABAergic Interneurons of the Striatum (chapter), Handbook of Basal Ganglia Structure and Function Handbook of Behavioral Neuroscience, Elsevier B.V., Oxford, UK, 2010
- Neurophysiology of Substantia Nigra Dopamine Neurons: Modulation by GABA (chapter), Handbook of Basal Ganglia Structure and Function, Handbook of Behavioral Neuroscience, Elsevier B.V., Oxford, UK, 2010
- Glutamatergic signaling by mesolimbic dopamine neurons in the nucleus accumbens, The Journal of Neuroscience, May 19, 2010
- Electrophysiolological and morphological characteristics and synaptic connectivity of tyrosine hydroxylase expressing neurons in adult mouse striatum, The Journal of Neuroscience, May 19, 2010
- Differential dopaminergic modulation of neostriatal synaptic connections of striatopallidal axon collaterals, The Journal of Neuroscience, July 15, 2009
- GABAergic afferents activate both GABAA and GABAB receptors in mouse substantia nigra neurons in vivo, The Journal of Neuroscience, October 8, 2008
- Feedforward and feedback inhibition in neostriatal GABAergic spiny neurons, Brain Research Reviews, November 1, 2007
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