Dr. Paul A. Garris
Dr. Paul A. Garris
Office - FSA 233, Labs – FSA 220, 225 and 227
Phone – 309-438-2664, Email - pagarri@ilstu.edu
Function and Regulation of Central Dopaminergic Neurons
My laboratory investigates the function and regulation of brain dopaminergic neurons. Although relatively few in number, these neurons play essential roles in animal behavior related to locomotion, cognition and motivation. Dysfunction of these neurons, moreover, leads to the debilitating human neuropathologies of Parkinson's disease, schizophrenia and drug abuse. A combination of real-time microsensors, behavioral and theoretical approaches is used in four main projects:
Fig. 1. Rat Dopaminergic Neurons
Parkinson's Disease
This neurodegenerative disorder, producing tremor, rigidity and akinesia, is clearly associated with the loss of nigrostriatal dopaminergic neurons. However, symptoms do not present until the degeneration is nearly complete. The absence of cardinal symptoms during the so called asymptomatic phase indicates the existence of potent compensatory neuroadaptations. Using a rat model, the primary goals of this work are to elucidate pre-clinical compensatory mechanisms and to identify behavioral deficits following mild to moderate dopaminergic lesions.
Neural Substrates of Sociosexual Behavior. The brain reward system mediates naturally reinforcing stimuli such as food, water and sex, and is also the target site of drugs of abuse. Although the mesolimbic dopaminergic neurons originating in the ventral tegmental area and terminating in the nucleus accumbens are intimately involved in this important circuitry, their precise role(s) is a current topic of debate. We are evaluating the role played by nucleus accumbens dopamine in motivation using sociosexual behavior of the Syrian hamster as a model. The female of this species exhibits an extended lordosis, a behavior characterized by a relatively immobile posture for up to 15 min, that makes this animal well suited for studies of this kind.
Stroke
The middle cerebral artery (MCA) perfusing the dopamine-rich striatum is commonly occluded in stroke. Interestingly, experimental occlusion of the MCA elicits a massive release of striatal dopamine, and prior dopamine depletion confers neuroprotection to striatal neurons. These results suggest that released dopamine drives ischemia-induced neurodegeneration. Our preliminary studies focus on short-duration MCA occlusion mimicking transient ischemic attacks, characterized by a temporary (<24 h) loss of neurologic function. We are also developing microsensors for the simultaneous measurement of dopamine, oxygen and pH, in order to provide a more integrated view of stroke neurochemistry.
Microsensor Development
To further our studies on brain-behavioral relationships, we are developing new instrumentation called Real-Time Animal Telemetry or RAT. The goal of RAT is wireless monitoring of brain chemistry and electrical activity during complex behavior. RAT overcomes a limitation of current technology by replacing the cable connector between a microsensor implanted in the brain and instrumentation with a telemetric device, similar to that used in digital cellular phones.