.jpg)
| Program | People | Events | Contact | Site Index | Printer Friendly |
| |||||||
| |||||||
| |||||||
| |||||||
| |||||||
|
Name, Field, Position, Department, and Keyword |
Faculty Keywords: caged neurotransmitters (1), Cell and Molecular Neuroscience (23), Ion channel (6), Ligand-activated ion channels (2), Neurotransmitter receptors and transporters (9), Patch clamp (2) We are investigating the structure and function of membrane-bound proteins (neurotransmitter receptors) that control and integrate communication between the cells of the nervous system. Malfunction of the receptors is implicated in many diseases of the nervous system, and the receptor proteins are the targets of a large class of clinically important compounds and abused drugs. Until recently investigation of the mechanism of action of these receptor proteins has been hampered by the lack of techniques with adequate time resolution (microseconds-to-milliseconds). My group has developed new biophysical techniques, most recently a laser-pulse photolysis method using caged neruotranmsitters, for investigating the receptors in cells isolated from specific areas of the nervous system to fill this gap. When a neurotransmitter binds to the active receptor forms, ion-conducting receptor-channels open, initiating electrical signals that transmit information in the nervous system. Whether or not a signal is transmitted depends on the concentration of open receptor-channels. This in turn depends on the neurotransmitter concentration and the length of time receptors are exposed to it. The immediate goal is to determine quantitative models, on a physiologically relevant time scale, for the chemical kinetic reactions of excitatory and inhibitory neurotransmitter [acetylcholine, gamma-aminobutyric acid, (GABA), glycine, glutamate, N-methyl-D-aspartate (NMDA) and serotonin receptors]. This goal has already been achieved with the nicotinic acetylcholine receptor from the electric organ (modified muscle) of certain fish. The eventual aim is to integrate all the available information into a consistent mechanism of signal transmission in the mammalian central nervous system. The chemical mechanism of neurotransmitter receptor-mediated reactions is expected to set limits to the various hypotheses concerning the operation of neuronal circuits and brain function, and to lead to an understanding of the effects of pharmacological agents and abused drugs on receptor function. An interdisciplinary approach, involving physical and organic chemistry, instrument development, molecular biology, electrophysiology, cellular neurobiology, and computer simulation, is being used to achieve these aims. |
Faculty Keywords: Cell and Molecular Neuroscience (23), Development (21), Drosophila (4), Genetics (9) One of two project areas in my lab is related to neuroscience. In this project we study molecules that modulate the reproductive capacity of mated female animals. We use Drosophila as a model for our studies, because of the genetic/genomic analyses it permits. In Drosophila, as in other animals with internal fertilization, males donate sperm and seminal fluid proteins to females during mating. In Drosophila females, seminal proteins (called ÏAcpsÓ for male ACcessory gland Proteins) stimulate egg production and ovulation, alter female mating behavior to decrease remating, aid in sperm storage, and affect the females' longevity. The ~80 Acps include peptide hormones (or their precursors), proteolysis regulators and other enzymes, protective peptides (e.g. antimicrobial peptides) and proteins (e.g. thioredoxin), and sperm- management proteins. We are identifying and characterizing the functions and targets of Acps, and the responses of females (at the molecular level) to these proteins. Our neuroscience-related work presumes that modulation of muscle contraction underlie some Acp effects such as ovulation, egg deposition, the movement of sperm into storage and their retention there. We tested whether mating or Acps affect vesicle release in the Drosophila female reproductive tract, by using a GFP-tagged vesicle protein, pro-ANF-EMD, that accumulates at nerve termini when expressed under the control of the elav promoter (fly line provided by D. Deitcher, Cornell NBB). When vesicles release pro-ANF-EMD, its fluorescence intensity drops. We used this system to assess vesicle release in the reproductive tracts of females that had mated to normal males or to males lacking Acps and/or sperm. We found that vesicle release is modulated in the reproductive tract after mating, and some of that modulation depends on Acps. Different regions of the reproductive tract respond independently and at different times. For example, 20 minutes after mating vesicle release is triggered at nerve termini in the lower reproductive tract, by the physical act of mating (not by Acps). Later, at the time of maximal ovulation and sperm storage, Acps inhibit vesicle release in the upper reproductive tract (sperm storage organs, oviducts). Our longterm aim is to identify the neuromodulators within these vesicles, and to correlate their release with Acp signaling (on the one hand) and the consequent response by the female (on the other hand). |
Please report corrections, questions, comments, and problems to: Lori Miller (lmm8 AT cornell.edu)