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Name: Matthew Oh
Title: Postdoctoral Fellow Degree: Ph.D. Research area: In Vitro Electrophysiology, Learning and Memory, and Aging Program: Neuroscience Address: Department of Physiology Northwestern University Medical School 303 East Chicago Ave. Chicago, IL 60611 Phone: (312) 503-3112 Fax: (312) 503-7912 Email:mattoh@northwestern.edu |
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Matthew Oh |
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Detailed research description: I am interested in understanding how we learn and, on the other side of the coin, why and how we forget – especially in cases of debilitating dementia, like Alzheimer’s disease. More specifically, I want to investigate and understand the neuronal processes (neural substrates, a “catch phrase”) involved in learning and forgetting to identify targets for pharmaceutical interventions to alleviate the symptoms of dementia and perhaps even prevent it. Thus, when it came to decide the school, program, and thesis advisor/mentor, the choice was simple (a “no brainer”) – Northwestern University’s Neuroscience program with Dr. Disterhoft as mentor. In Dr. Disterhoft’s lab, I was able to take advantage of four key discoveries of the lab. First, the foundation of all subsequent work, Dr. Disterhoft during a sabbatical in Dan Alkon’s lab in mid-1980’s discovered that the postburst afterhyperpolarization and spike-frequency adaptation are reduced in CA1 pyramidal neurons of rabbits that have acquired the delay eyeblink conditioning task, a Pavlovian classical conditioning paradigm. This discovery was followed up and elaborated in two key papers in Journal of Neuroscience and Journal of Neurophysiology in 1996 by Jim Moyer, Tres Thompson and Dr. Disterhoft. In these papers, they expanded upon the previous discovery and demonstrated that (2) the reductions of the postburst afterhyperpolarization and spike-frequency adaptation in hippocampal pyramidal neurons are a learning-dependent phenomena observed after acquisition of trace eyeblink conditioning, a hippocampal-dependent associative learning task. Furthermore, they demonstrated that the biophysical changes of the hippocampal pyramidal neurons are transient, lasting approximately a week; providing a key support to the idea that the hippocampus serves an “intermediary” role for permanent memory, which is thought to be stored in the cortex. In the same year, 1996, another key paper was published in Neurobiology of Aging by Tres Thompson, Jim Moyer and Dr. Disterhoft. In this paper, they demonstrated that (3) the trace eyeblink conditioning task is difficult for aging rabbits: with increasing age, there is a greater proportion of animals that fail to acquire this task and, for those that do acquire the task, they need more trials than the young to learn the task. The fourth key discovery (which was replicated by me and John Power in 1999) is the demonstration that the postburst afterhyperpolarization and spike-frequency adaptation are greater in hippocampal pyramidal neurons from aging rabbits compared to those of the young (paper by Jim Moyer, Tres Thompson and Dr. Disterhoft in 1992). Furthermore, the postburst afterhyperpolarization and spike-frequency adaptation are reduced in hippocampal pyramidal neurons from aging rabbits that have acquired the trace eyeblink conditioning task, like that observed in young rabbits (Moyer et al. Journal of Neuroscience 2000). Thus, to simplify, the working hypothesis for me (and others in the lab) is the age-related deficit observed in associative learning tasks is due to the enhanced postburst afterhyperpolarization and spike-frequency adaptation; hence, increasing neuronal excitability of hippocampal pyramidal neurons may reverse or alleviate the age-related learning deficits. To this end, I have been using sharp-electrode current-clamp recording technique to record biophysical properties of CA1 pyramidal neurons from hippocampal slices of animals (rabbits and rats) that have 1) either been trained or pseudoconditioned, 2) been treated with “cognitive enhancers”, and 3) examined the effects of several “cognitive enhancers” on hippocampal pyramidal neurons of both young and aging naïve animals. For my curriculum vitae, including list of publications, please click here
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