The Neuroscience training faculty are excellent and well-supported researchers and teachers. The group includes recipients of the National Institutes of Health Javits Awards for excellence in neuroscience, NIH Merit and Career Development Awardees, and Alfred P. Sloan Foundation Fellows.
The training faculty are selected from four basic science and five clinical departments, Biochemistry/Biophysics/Genetics, Cellular and Developmental Biology, Pharmacology, Physiology, Radiology, Medicine, Neurology, and Psychiatry, carrying out their research in close collaboration with their graduate students and postdoctoral associates.The Neuroscience faculty constitute a good balance of tenured and young professors who participate in exciting and beneficial collaborations in both teaching and research projects.
The Neuroscience Training Program at the University of Colorado provides multidisciplinary training covering the breadth of neurobiology, from neuronal gene regulation to the development, structure, and function of the nervous system. Students receive training in cellular and molecular neurobiology, neural development, neuropharmacology, and biochemistry, as well as hands-on training in a variety of state-of-the-art laboratory techniques.
The tremendous advances in molecular biology during the past few decades have greatly enhanced research in the neurosciences. Specific macromolecules important in neuronal function have been identified and characterized with increasing frequency. The mechanisms by which these molecules act, and the cellular controls over their genetic expression have begun to be elucidated. Our studies are concerned with all of these aspects of molecular neuroscience.
The brain shows a higher complexity in its RNA when compared to other organs. More unique sequence single copy DNA is transcribed and found associated with polysomes in brain than in any other tissue. The functional significance of this complexity is unknown. Many of these mRNAs occur less than one copy per every ten cells, suggesting a high degree of cellular specificity in neural gene expression. How neural gene expression is regulated is an area of active interest among our faculty.
In part neural genes are regulated in response to specific growth factors (e.g., nerve growth factor), hormones, and neurotransmitters. Although some of these molecules act by binding to cytoplasmic receptors, many of them act by binding to specific cell surface receptors, some of which are subsequently internalized as a complex, while others act by transmembrane signalling of their binding via membrane proteins coupled to GTP binding proteins or polyphosphoinositide--diacylglycerol generation. These signalling systems act to alter the activity of intracellular protein kinases, which act to influence gene transcription, ion channels, and neurotransmitter release and reception. The interaction of neurotransmitters and growth factors with their receptors, signal transduction mechanisms and the role of protein phosporylation in the function of specific neural proteins are a major focus of our research.
Recombinant DNA technology and gene cloning procedures are used routinely in many of these studies. The availability of a mouse brain genomic library and expression systems puts essentially every gene of interest within reach, and permits an analysis of gene expression and functional aspects of the gene product.
Cells of the nervous system are some of the most unique cells found in organisms. Many of these cells have evolved sophisticated structures and mechanisms to sense the slightest differences in light, color, sound, taste, smell, touch, etc. The neurons which transmit this information are not only unique cells but are among the most highly specialized of all cells, both structurally and functionally. Long threadlike processes (axons and dendrites) may stretch a meter or more from the cells nucleus, making highly specific synaptic connections with other cells. Functionally these neurons respond by sending electrical signals in the form of action potentials brought about by the opening and closing of specific ion channels. The action potential is rapidly and efficiently transmitted along these delicate processes. At the axon terminus special chemicals (neurotransmitters) are synthesized, packaged and, upon arrival of an action potential, secreted into the synaptic cleft. The secreted neurotransmitters bind to specific receptors on adjacent neurons and modify their electrical and metabolic activity.
The basic mechanisms of these numerous and different ion channels that are responsible for the unique properties of neurons are being actively pursued by our faculty. They are using a variety of biochemical, pharmacological and electrophysiological techniques including patch clamp recording of single ion channels. Neurotransmitter receptors are being localized and quantified in neural tissue using radiolabelled ligands and computer based image processing of autoradiographs. Other faculty are characterizing these sensory cells and their connecting pathways in the CNS with modern electron microscopic, elctrophysiological and immunochemical procedures.
The development of the brain is one of the most complex phenomena in biology. A dynamic interplay between genetic and environmental cues guides the proliferation, migration and differentiation of neurons and glial cells, as well as the outgrowth of axons and their guidance to and recognition of appropriate target cells. From studies of specific molecules to expression of emergent behavior, our faculty are actively involved in developmental neuroscience.
At early times in neural development, proliferating neuroblasts cease dividing in response to yet unknown signals. They then begin to express differentiated properties including axonal outgrowth, and most undergo cell migration. Axon formation is initiated by the post-mitotic neuron and usually proceeds in the direction necessary to reach its appropriate target. The axonal growth cone is the dynamic motile structure that searches out the target. Externally the growth cone possesses neural cell adhesion molecules and other cell recognition molecules that interact with cellular and extracellular molecules to guide the axon toward its synaptic target. Developing and regenerating axonal growth cones possess unique molecules, including a growth associated protein, as well as the ability to secrete proteases such as plasminogen activator; the roles these specific neuronal molecules play in development are areas of active interest among our faculty.
Similarly, the cell recognition mechanisms associated with axonal pathfinding, synaptogenesis, and the molecular and physiological mechanisms for the stabilization of these synapses, as well as the elimination of multiple synapses are major areas of faculty research.
Some of the most obvious, interesting and widespread aspects of behavioral neuroscience are those associated with particular disease states. Especially notable are the movement defects that affect tens of thousands of individuals with Parkinsons disease, and the memory loss and confusion associated with Alzheimers disease in many senior citizens. Both of these disorders reflect the loss of specific cell populations in the substantia nigra and basal forebrain, respectively.
One of the most recent and exciting approaches to the treatment of these disorders is the use of nerve cell transplants. Our faculty have been pioneers in the field of intraocular and brain transplants. Currently they are actively pursuing the use of fetal brain tissue grafts in animal models, to gain a better understanding of the requirements for graft survival and their interaction with host tissues to restore functional behavior in these brain regions.
Other faculty are studying the action of various behavior altering drugs on specific neurons and their electrical and synaptic activity. Their development of miniaturized electrochemical electrodes for monitoring neurotransmitter release in specific brain regions has greatly enhanced such analysis. The biological action of various neuropeptides, specifically those related to pain, are being characterized at the molecular level using modified synthetic peptides in animal models.
Faculty and Research Specializations