Statement of Research Interests-Jeff Hollerman

Brain cells that utilize the neurotransmitter dopamine comprise only a small fraction of the billions of neurons that make up the human central nervous system. Despite their relatively small number and their circumscribed location in the ventral regions of the evolutionarily ancient midbrain, these dopamine neurons have been implicated in an almost bewildering variety of functions, ranging from basic processes involved in the control of movement and reinforcement to the more complex functions involved in drug addiction and cognition. The role of dopamine and dopamine-containing neurons in such diverse and important functions has made the central dopamine systems the subject of extensive experimental research but we are only beginning to appreciate the ways in which this single neurotransmitter originating in a small population of cells can produce such diverse effects on behavior and mental processes. My current research interests focus on the role of dopamine in reinforcement, drug addiction and cognition.

Reward/reinforcement

There is considerable evidence for the role of dopamine in the reinforcing properties of both natural rewards and addictive drugs. All addictive drugs, regardless of their primary mechanism of action, have been shown to increase release of dopamine in the ventral striatum, as have natural reinforcers such as food, water and sex. Electrical stimulation of dopamine containing neurons that project to the ventral striatum has also been shown to have reinforcing properties. While these observations suggest that dopamine release itself is reinforcing, recent electrophysiological investigations of dopamine neuron activity have shown that these neurons are particularly sensitive to the predictability of reward occurrence. These new findings raise intriguing possibilities regarding the nature of the dopamine signal and how if influences learning in natural situations, as well as how drug effects on this system can produce addiction.

Cognition

Perhaps the most prominent observation indicating that dopamine is also involved in higher cognitive processes is the fact that the profound cognitive symptoms of schizophrenia are currently most effectively treated with drugs that block the action of dopamine. This observation formed the basis for the"dopamine hypothesis" of schizophrenia, which in its simplest form asserted that schizophrenic symptoms arose from an excess in dopamine function. Recent technological advances and the corresponding new information they have provided have led to a variety of modifications to this dopamine hypothesis, but the presence of an abnormality in dopamine function in schizophrenia is not contested. Current hypotheses focus on an imbalance between cortical and subcortical dopamine function, although many researchers suggest that this is itself a secondary dysfunction, caused by a primary abnormality in another system.

Autism

Autism is a pervasive developmental disorder (PDD) characterized by impairments in social, communication, and behavioral skills, with symptoms appearing before the age of three. Since it was first described by Leo Kanner in 1943, there have been a variety of theories regarding the origins of autism, but no single theory has emerged that accounts for the entirety of the disorder. Increasing evidence has accumulated indicating a neurodevelopmental abnormality, although both the nature of the developmental insult and the anatomical sites affected are currently subject to considerable debate. One way to help to resolve these differences is to use an animal model to investigate the effects of a developmental insult on anatomy and behaviors that parallel those observed in autistic individuals. Prenatal exposure of rats to valproic acid is being used as a valuable model for pursuing investigations into the origins and substrates of, as well as potential treatments for, autism. Anatomical, behavioral and electrophysiological studies should all provide useful information on the model and hopefully the disorder itself.