A major technology development focus is the dynamics of neurotransmitter function in the central nervous system.  In order to perform such studies, his lab develops microelectrode arrays (MEAs) and instrumentation for the rapid, sensitive, and spatially resolved measurement of neurotransmitters and neuromodulators, such as dopamine, norepinephrine, serotonin, nitric oxide, glutamate, GABA, acetylcholine, ATP, oxygen, peroxide and adenosine.  His lab developed the ceramic-based microelectrode array technology that is currently being used in his laboratory and others to better understand rapid neurotransmitter signaling in the normal, aged and diseased brain. A major goal of these studies is to understand neurotransmitter signaling in biological systems on a second-by-second time scale.  This forms the basis for the Center for Microelectrode Technology, which was started with a mandate from NSF in 1991. In addition, his laboratory designs the MEAs that are being used to develop the BMI device with Dr. Ted Berger (USC) and Dr. Rob Hampson (Wake Forest) to repair the hippocampus in memory- impaired animals and may lead to a cortical prosthetic device for use in humans.

Dr. Gerhardt’s laboratory focuses on studies of movement abnormalities in aging, specifically Parkinson’s disease and parkinsonism.  Such studies are performed in the striatum of young and aged Fischer 344 rats, and in young and aged nonhuman primates. For these studies, his lab uses both the 6-hydroxydopamine-lesioned rat model and the MPTP-lesioned primate model of Parkinson’s disease.  Using his microelectrode techniques, Dr. Gerhardt’s lab has investigated the release and uptake of dopamine in the striatum of the normal and parkinsonian brain.  A major finding for these studies is that there is a severe disruption of dopamine regulation in the parkinsonian brain.  This disruption of the control of dopamine may relate to some of the movement problems seen in this CNS disease.  His laboratory has been investigating the use of growth factors, such as GDNF, to restore function to damaged dopamine neurons in Parkinson’s disease. His group was instrumental in the Phase I/II clinical studies of patients with Parkinson’s disease that was carried-out at his Udall Center and was sponsored by Amgen. Additional pre-clinical studies are now underway with a new venture with Medtronic and Eli Lilly to get GDNF back into clinical trials in the next 2 years. Dr. Gerhardt was awarded a Research Career Development Award (RCDA; 1989-1994) from the NIA and he received a Level II Research Scientist Development award (RSDA; 1995-2000) from the NIA. He has had consistent NIH funding at the RO1 and PO1 or P50 levels throughout his career. In addition, he has directed a T32 Training grant with 4 pre-doctoral and 2 postdoctoral slots from NIA since 2009.  He has more recently developed the Brain Restoration Center in conjunction with Dr. Craig van Horne in Neurosurgery.  He completed MER training for DBS Surgeries in 2012.  He currently assists Dr. van Horne in DBS surgeries in conjunction with the newly formed Brain Restoration Center. Currently, the DBS group implants ~60-80 patients per year and has obtained the status as top 10 of over 300 DBS treatment centers by Medtronic, Inc. 

Given the importance of glutamate systems in memory, it is our central hypothesis of the Gerhardt laboratory that changes in the dynamic functional properties of glutamate and GABA signaling in the hippocampus and frontal cortex in the CNS contribute to age-related declines in motor function, cognition and memory in aging and Alzheimer’s disease (AD). Our recent studies using enzyme-based microelectrode arrays (MEA) support that dynamic changes to glutamate release and glial uptake systems occur in aging and are regionally heterogeneous in the striatum and hippocampus. Prior data supporting aberrant changes to glutamate and GABA systems in aging in individual brain structures, such as the rat and mouse hippocampus, are equivocal due to four major reason: 1) aging of glutamate and GABA neurons affects different cellular compartments, 2) tonic (resting) and phasic (spontaneous bursts) glutamate and GABA release in freely moving animals must be measured in sub-regions of brain structures over 24 hour periods to determine the effects of aging on glutamate and GABA systems and 3) AD pathology may affect tonic (resting) and/or phasic release of glutamate, GABA, and their ratios, which can affect the excitatory/inhibitory balance and 4) the aging process is heterogeneous among animals, resulting in at least 2 groups of animals that are behaviorally impaired or unimpaired.  A major goal is to determine changes to glutamate and GABA regulation in the mouse hippocampus and frontal cortex using our MEA recording technology to study tonic (resting) and phasic (spontaneous bursts) glutamate and GABA in freely moving mice. We investigate the glutamate and GABA systems in the hippocampus and frontal cortex during aging and in a mouse model of AD. We also use behavioral tests to correlate age-related and AD model changes in glutamate and GABA using the Barnes maze (hippocampal measures), and a spatial working memory variant of the Morris water maze testing (frontal measures) to determine the behavioral capabilities of the animals. Taken together, these studies should contribute to a better understanding of the dynamics of glutamate and GABA regulation in AD and glutamate and GABA dynamics in an AD model and aging of the CNS.

Our lab also conducts studies in normal aging showing that dopamine and norepinephrine synapses change in their ability to regulate neurotransmitter release through changes in the monoamine transporters.  In addition, recent work from his group has determined dynamic age-related changes in glutamate regulation in the rat striatum and hippocampus. These studies are the first to look at second-by-second regulation of glutamate in sub-regions of the rat striatum and hippocampus that are involved with Parkinson’s disease and Alzheimer’s disease.

Historically, Dr. Gerhardt’s research group has also been extensively involved in neuropsychopharmacology and the development of new drugs to treat depression, mania, schizophrenia and attention deficit hyperactivity disorder (ADHD). Dr. Gerhardt was awarded a 5-year KO2 (RSDA) from NIMH from 2000-2005.