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Department of Physiology and Biophysics

University of Colorado Department of Physiology and Biophysics
 

Research




Nathan Schoppa, who joined our faculty in 2003, studies mechanisms of olfaction - the sense of smell. The first level of neural processing of odors is performed in a brain structure named the olfactory bulb. The regular arrangement of neurons in the olfactory bulb make it a good model for other, more complex, brain regions. Dr. Schoppa has identified several novel mechanisms by which nerve cells in the olfactory bulb communicate with each other.One example, involving the concerted action of chemical neurotransmitters and electrical gap junctions, leads to the synchronization of electrical discharges (called action potentials) in different neurons. Such processes may help higher brain centers decode information and discriminate between different odors.

The goal of the work in Dan Tollin's lab is to understand the neural mechanisms of auditory perception with particular emphasis on how sources of sounds are localized. Because the peripheral receptors of the ear have no mechanism to directly sense sound location on their own (unlike the topographic organization of the retina), location must be computed at more central levels. This makes sound localization a fascinating neurocomputational problem, particularly from a developmental perspective.

Sukumar Vijayaraghavan joined our faculty in 1997 after completing postdoctoral work at the University of California at San Diego. Dr. Vijayaraghavan ('Suke') has played an important role in studies of nicotinic receptors in the nervous system, a field that is experiencing rapid and exciting advances. The physiological function of these receptors, which are ordinarily excited by acetylcholine (and, in smokers, by nicotine), is not very well understood. Dr. Vijayaraghavan brings experience with a broad array of tools - including biochemistry, electrophysiology, and imaging - to bear on his studies of the receptors.

Angie Ribera and colleagues are interested in the development of the nervous system, in particular how neurons acquire the characteristics that enable them to produce electrical signals with exquisite sensitivity and speed. Very young neurons give sluggish signals, but as they develop the signals become crisper and sharper. These characteristics arise as new ion channels appear in their membranes. Dr. Ribera in particular is interested in channels that permit potassium ions to cross the membrane; it is these channels that are responsible for the maturation of the electrical signaling capability of the developing cells.

Rock Levinson pioneered biochemical studies of one of the most fundamental molecules in the nervous system - the sodium channel. This molecule underlies all electrical signaling in the nervous system. The first person to purify biochemically the sodium channel, Dr. Levinson currently is examining the role that myelin plays in governing the spatial distribution of sodium channels. Myelin is an electrical insulator that insures proper conduction of electrical signals in the nervous system. Loss of myelin underlies the pathology in multiple sclerosis.
Sodium channels are proteins, but they also have sugar molecules attached to them. The sugars have subtle but important effects on the behavior of the channels, and Dr. Levinson studies the molecular and cellular mechanisms by which the channel protein is sweetened with sugars.

Peggy Neville studies the mechanisms by which milk is secreted. Milk is an almost miraculous fluid that contains all the nutrients, vitamins and minerals needed to nourish the offspring of mammals for some time after birth. It also contains important factors that promote infant growth and immune development as well as protective substances that help prevent bacteria and viruses from causing disease in the young. Dr. Neville and colleagues are interested in the cellular and molecular mechanisms by which many of these substances are taken from the mother's blood stream and transferred into the milk. They are studying lactoferrin, an iron binding protein that also has antibacterial properties and regulates the activity of the immune system. Dr. Neville also studies how fats get into milk and has discovered a new pathway for the secretion of lipoproteins, and are examining the regulation of the tight junctions that isolate newly formed milk from the rest of the body.

The people in the lab of Bill Betz study the cellular mechanisms by which substances are secreted from cells. The process, called exocytosis, involves fusion of intracellular vesicles that contain the materials to be secreted. Then the empty vesicles are recaptured by the cell (endocytosis) and refilled, making them ready for another round of secretion. The process occurs in all cells, but is especially prominent in the nervous system, where neurotransmitters are secreted at specialized junctions between cells (synapses). Dr. Betz and colleagues developed special dyes that label the vesicles, making it possible to observe exocytosis and endocytosis through a microscope as it occurs in living cells.

The major focus of Celia Sladek's laboratory has been understanding the mechanisms that regulate gene expression and secretion of the hormones, vasopressin (also called antidiuretic hormone) and oxytocin. They are produced by neurons in the hypothalamus, are released from the neurohypophysis into the blood stream, and regulate respectively the two functions that are hallmarks of mammalian physiology: formation of a concentrated urine by the kidneys and mammary gland function.  The neurons that produce these hormones also represent an important model system for studying neuronal responses to neurotransmitters.  We are currently studying the cellular mechanisms underlying synergistic responses to co-released neurotransmitters as well as the ability of some G-protein coupled receptors to directly regulate gene expression by translocating to the nucleus. Hormone release, live cell imaging, immunohistochemistry, and western blot analysis are currently employed in these studies.

Kurt Beam's laboratory addresses the function of calcium channels in nerve and muscle.  In muscle, contraction depends on communication between a calcium channel (the “DHPR”) located in the plasma membrane and a channel (the “RyR”) located in an intracellular membrane system.  Our long term goal is to understand the protein-protein interactions that underlie the signaling between DHPR and RyR in muscle and the similar kinds of signaling that occur in nerve.  For this, we express cDNAs in cultured cells from mice with null mutations in the RyR and in subunits of the DHPR.  The protein-protein interactions are studied electrophysiologically, by fluorescence resonance energy transfer and biochemically.  In addition to answering questions about a basic cellular function, the research also bears on inherited human diseases that result from mutations in calcium channels.

Cathy Proenza's lab studies pacemaking in the sinoatrial node of the heart.  Spontaneous activity in individual sinoatrial myocytes triggers contraction of the heart, and the autonomic nervous system changes heart rate by regulating this spontaneous firing rate.  The laboratory uses electrophysiology, biochemistry, and imaging techniques to study the molecular basis for pacemaking in single sinoatrial cells, the synapses between autonomic neurons and sinoatrial cells, and the macromolecular complexes and intracellular signaling pathways that link neural activity to changes in heart rate.

The lab of Achim Klug is interested in the question how streams of auditory information are processed by neurons in the auditory brainstem, and how certain neuronal properties shape the processing of this information. Some neurons in the auditory brainstem, especially those involved in the computation of spatial information, are among the fastest in the brain. They possess a number of interesting features that increase temporal precision, such as specialized channels or synapses, or specialized morphology. The main research goal is to understand these features, but also to understand how the system as a whole functions in the processing of incoming sound information.

Gidon Felsen's lab is interested in the neural mechanisms underlying goal-directed behavior.  Animals are remarkably adept at using sensory stimuli to decide on and implement their best course of action, but how the nervous system mediates these processes is largely unknown.  The lab adresses this question by recording and manipulating neural activity rodents performing behavioral tasks.  Ultimately, this research seeks to understand howmotor actions are selected and initiated in the normal and disease states.

Abigail Person’s laboratory studies the contribution of the cerebellum to motor control, focusing on circuit mechanisms that support smooth, precise movement.  A central idea in cerebellar physiology is that the position of the body is monitored via copies of motor commands conveyed by “corollary discharge pathways”. By combining physiology, optogenetics and anatomical methods, we study the structure and function of a corollary discharge pathway into the cerebellum, addressing how it is processed by postsynaptic circuitry and modifies other afferent pathways. These topics are at the heart of the role of the cerebellum as a sensorimotor integrator. Disorders of this circuitry are hypothesized to contribute to some aspects of disorders such as autism and schizophrenia as well as broad motor disturbances seen in cerebellar ataxias.


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