Research Interests:

Synaptic plasticity and functional recovery after injury and disease in the mature and aged central nervous system.

He earned his Bachelor of Arts degree in 1962 from Wooster College, majoring in chemistry. He received his master.s degree in analytical chemistry from Wesleyan University in 1964 and continued his training at Indiana University where his dissertation on the isolation and characterization of synaptic membrane proteins earned him his Doctorate in 1968. Thus, Dr. Cotman's early background was in the field of analytical chemistry before he received special training in the chemistry of the nervous system.

A statement from the Director:

Our goal is to determine the nature of natural healing processes in the nervous system and to develop new therapeutic interventions. In most organs, cells can divide and thus replace those lost due to injury or disease. In contrast, most nerve cells do not divide. Therefore, for many years, the brain and spinal cord were believed to have little if any ability to repair damaged circuits. This belief, however, conflicted with clinical experience showing that patients at least partially recover from minor injuries, i.e., trauma, stroke, and short-term degenerative diseases. Our research centers on studying the mechanisms by which recovery may be achieved and on facilitating such recovery, e.g., by enhancing the growth and compensatory reorganization of remaining connections, and injecting factors which facilitate the repair of damaged circuits.

Our work and that of others has shown that following the loss of neurons in the hippocampus of rodents, the remaining fibers from healthy nerve cells grow collateral sprouts and make new synapses to replace those lost, a process known as reactive synaptogenesis (the formation of new nerve connections). Reactive synaptogenesis may facilitate functional recovery in cases involving partial cell loss within a defined neuronal population by stabilizing the circuits, counteracting further cell loss, and preventing potentially greater functional decline. It is the natural repair process for cell loss in the central nervous system.

Research over the past ten years on sprouting and reactive synaptogenesis using the rodent hippocampal formation as a model system has progressed to the point where it is possible to predict which responses might occur in humans. In Alzheimer.s disease, neurons are lost slowly over time as the brain degenerates. Data from our lab and others across the country indicate that a selective robust sprouting reaction occurs in the damaged hippocampal pathways within the brain of Alzheimer.s patients. In essence, such actions rebuild the circuits to defend the brain from the loss of its neurons.

Our main goal is to study the molecular mechanisms underlying reactive growth in the brain in order to develop new therapies along the brain.s natural lines of defense. It now appears that maintenance and plasticity depend on rapid signaling via conventional neurotransmitters and long-term signaling via neurotrophic factors (molecules which enhance cell growth or survival). Many of the transmitters in the reactive pathways are excitatory amino acids such as glutamate and aspartate. Current work centers on the study of receptors in postmortem brain tissue from patients with Alzheimer.s disease. Other current work involves molecular analysis of the regulation of neurotrophic factors and the processing and properties of B-amyloid, a protein that accumulates in Alzheimer.s disease. What is the precise nature of the growth factors for certain types of cells, and what controls their production?

We are also pursuing parallel clinical studies on dementia patients in collaboration with various clinicians at the UCI College of Medicine. We are using new imaging methods [e.g., magnetic resonance imaging (MRI) and magnetic resonance spectroscopy (MRS)] to examine the functions of the brain regions that demonstrate plasticity in Alzheimer.s patients. We are conducting parallel animal studies to test the behavioral functions of the same circuits.

It is our conviction that one of the next major areas in the neurosciences is that of clinical psychobiology. We have an active program within the laboratory, within the Department of Psychobiology, Neurology, and among other UCI departments toward this end.