Laboratory research projects focus on specific neural networks in the brain and their role in neurological disorders. Currently, special attention is devoted to the limbic system and the basal ganglia, with respect to glutamate and GABA-mediated influences on epileptic seizures and memory. Also under investigation are neural substrates of Parkinsonism and cocaine-induced hyperkinesias.

My co-workers and I have identified the substantia nigra as a critical site of action of GABA agonists and glutamate antagonists for protecting against experimental seizures. We have discovered a crucial site in the prepiriform cortex (named area tempestas) of the rat and monkey, from which complex partial epileptic seizures can be triggered. Our current research is aimed at determining how GABA, glutamate, serotonin, and norepinephrine interact in these brain regions to influence forebrain excitability.

In experiments, drugs are applied into discrete regions of the brain of awake animals to selectively manipulate local synaptic transmission. Acute behavioral and EEG seizure activity are evaluated, as well as short and long term molecular changes (e.g., in the expression of genes encoding neurotrophic factors) in response to seizure activity.

Related projects under development include: a) patch clamp recordings of area tempestas neurons in brain slices; b) the use of viral vectors to manipulate the genetic expression of enzymes involved in the synthesis of certain neurotransmitters in specific brain regions in vivo in an attempt to reduce seizure susceptibility; c) positron emission tomography (PET) studies of changes in regional brain metabolism during seizures; and d) determining the role of glutamate transmission in piriform cortex for recognition memory.

Selected Publications: