The proposed research concerns synaptic transmission, voltage dependent ionic conductances, and the relation between them, in bullfrog sympathetic and rodent hippocampal neurons. The main technique used is voltage clamp. This allows one to separate and in favorable cases quantitate, the various inward and outward currents present. This will allow reconstruction of the totality of the electrical behavior of these cells. Also, the effects of neurotransmitters and of synaptic stimulation on these individual currents can be determined. In turn this enables prediction of the effects of slow synaptic inputs on neuron electrical behavior. The main difference between ganglia and hippocampal neurons is in difficulty of experiment and interpretation. Bullfrog neurons are relatively accessible and robust, and lack complex processes which cause space clamp problems. Hippocampal neurons are less tractable in all 3 aspects, but are more relevant to clinical problems. In both cases fresh and cultured material will be used. The main thrust will be on the muscarinically-controlled outward currents IM and IAHP which have been previously characterized by this laboratory. Because these are novel conductances they are still not thoroughly understood. The mechanisms linking muscarinic receptor to these channels, and the features of the channels themselves, are largely unknown. Various patch clamp techniques will be used to explore this question. This research has relevance to epilepsy and Alzheimer's disease, the former because the data obtained will help explain abnormal neuronal excitability, and the latter because data concerning cortical cholinergic actions will be forthcoming.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
5R01NS018579-06
Application #
3398575
Study Section
Physiology Study Section (PHY)
Project Start
1982-07-01
Project End
1990-06-30
Budget Start
1987-07-01
Budget End
1990-06-30
Support Year
6
Fiscal Year
1987
Total Cost
Indirect Cost
Name
State University New York Stony Brook
Department
Type
Schools of Arts and Sciences
DUNS #
804878247
City
Stony Brook
State
NY
Country
United States
Zip Code
11794
Hernandez-Cruz, A; Sala, F; Adams, P R (1990) Subcellular calcium transients visualized by confocal microscopy in a voltage-clamped vertebrate neuron. Science 247:858-62
Brown, D A; Higashida, H; Adams, P R et al. (1988) Role of G-protein-coupled phosphatidylinositide system in signal transduction in vertebrate neurons: experiments on neuroblastoma hybrid cells and ganglion cells. Cold Spring Harb Symp Quant Biol 53 Pt 1:375-84
Storm, J F (1987) Action potential repolarization and a fast after-hyperpolarization in rat hippocampal pyramidal cells. J Physiol 385:733-59
Jones, S W (1987) A muscarine-resistant M-current in C cells of bullfrog sympathetic ganglia. Neurosci Lett 74:309-14
Adams, P R (1987) Cholinergic hypothesis of Alzheimer's disease: biophysical aspects. Res Publ Assoc Res Nerv Ment Dis 65:169-85
Storm, J F (1987) Phorbol esters broaden the action potential in CA1 hippocampal pyramidal cells. Neurosci Lett 75:71-4
Satin, L S; Adams, P R (1987) Spontaneous miniature outward currents in cultured bullfrog neurons. Brain Res 401:331-9
Brown, D A; Adams, P R (1987) Effects of phorbol dibutyrate on M currents and M current inhibition in bullfrog sympathetic neurons. Cell Mol Neurobiol 7:255-69
Jones, S W (1987) Luteinizing hormone-releasing hormone as a neurotransmitter in bullfrog sympathetic ganglia. Ann N Y Acad Sci 519:310-22
Jones, S W (1987) Sodium currents in dissociated bull-frog sympathetic neurones. J Physiol 389:605-27

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