We shall utilize fura-2 based microspectrofluorimetry and imaging techniques to investigate the regulation of (Ca2+)i in vertebrate neurons from the central and peripheral nervous systems. In the first series of studies we shall investigate the properties of intracellular bound stores of Ca2+ within neurons. We shall ascertain the distribution of these stores and whether they can be regulated by methylxanthines such as caffeine or by inositol trisphosphate (IP3). Furthermore, we shall investigate the effect of various neurotransmitters on phospholipid metabolism in different types of central and peripheral neurons in vitro. Secondly, we shall also continue to investigate the different types of voltage sensitive Ca2+ channels found in vertebrate neurons. In particular we shall investigate the distribution of different types of Ca2+ channels in single neurons in vitro. We shall also continue to investigate the mechanism by which neuronal Ca2+ currents can be regulated by neurotransmitters and whether this modulation occurs in different parts of the neuron. We shall continue to analyze the molecular basis for Ca2+ current modulation in neurons and in particular the role of G-proteins and protein kinase C in this process. We shall also continue to investigate receptor operated Ca2+ channels in neurons, particularly those activated by the excitatory amino acid glutamate. We shall continue to characterize the ionic channels linked to these receptors and the way that they can be modulated by low concentrations of glycine. Finally, we shall attempt to measure changes in (Ca2+)i in neurons in slice preparations from the central nervous system. In such a situation the cells will be in a more """"""""normal"""""""" environment. We hope to be able to characterize changes in (Ca2+)i occurring in CA1 pyramidal cells during the induction of long term potentiation and to assess whether such changes are sine quae non for the establishment of this phenomenon.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Method to Extend Research in Time (MERIT) Award (R37)
Project #
5R37MH040165-10
Application #
2244908
Study Section
Special Emphasis Panel (NSS)
Project Start
1985-06-01
Project End
1998-05-31
Budget Start
1994-06-01
Budget End
1995-05-31
Support Year
10
Fiscal Year
1994
Total Cost
Indirect Cost
Name
University of Chicago
Department
Pharmacology
Type
Schools of Medicine
DUNS #
225410919
City
Chicago
State
IL
Country
United States
Zip Code
60637
Bhattacharyya, Bula J; Wilson, Scott M; Jung, Hosung et al. (2012) Altered neurotransmitter release machinery in mice deficient for the deubiquitinating enzyme Usp14. Am J Physiol Cell Physiol 302:C698-708
White, Fletcher A; Miller, Richard J (2010) Insights into the regulation of chemokine receptors by molecular signaling pathways: functional roles in neuropathic pain. Brain Behav Immun 24:859-65
Thomas, Ajit G; Bodner, Amos; Ghadge, Ghanashyam et al. (2009) GCP II inhibition rescues neurons from gp120IIIB-induced neurotoxicity. J Neurovirol 15:449-57
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Abbadie, Catherine; Bhangoo, Sonia; De Koninck, Yves et al. (2009) Chemokines and pain mechanisms. Brain Res Rev 60:125-34
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Belmadani, Abdelhak; Jung, Hosung; Ren, Dongjun et al. (2009) The chemokine SDF-1/CXCL12 regulates the migration of melanocyte progenitors in mouse hair follicles. Differentiation 77:395-411
Jung, Hosung; Miller, Richard J (2008) Activation of the nuclear factor of activated T-cells (NFAT) mediates upregulation of CCR2 chemokine receptors in dorsal root ganglion (DRG) neurons: a possible mechanism for activity-dependent transcription in DRG neurons in association with neuropathic Mol Cell Neurosci 37:170-7
Jung, Hosung; Toth, Peter T; White, Fletcher A et al. (2008) Monocyte chemoattractant protein-1 functions as a neuromodulator in dorsal root ganglia neurons. J Neurochem 104:254-63

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