Abstract

The principal goals are: a) to develop antisense nucleic acid methodologies for disruption of gene expression in cells of interest in neurobiology; b) to apply these methods to problems of signal transduction, and of ion channel and neurotransmitter reception function. Studies will be carried out in NGF-induced PC-12 cells, with a focus on Na+ and Ca2+ channels, and on their modulation by G protein coupled systems. Problems of interest include the sequence identity of the Ca2+ channel genes expressed and their spatial distribution between neurites and somites. Assays will be by electrophysiology and by sensitive RNA analysis. Additional studies in oocytes will focus on the identification of the epitopes within G proteins that are important for interactions with 7 helix receptors and effectors.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Specialized Center (P50)
Project #
5P50MH049176-05
Application #
5214808
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
5
Fiscal Year
1996
Total Cost
Indirect Cost

  Publications

Sokolova, Irina V; Lester, Henry A; Davidson, Norman (2006) Postsynaptic mechanisms are essential for forskolin-induced potentiation of synaptic transmission. J Neurophysiol 95:2570-9
Schwarz, Johannes; Schwarz, Sigrid C; Dorigo, Oliver et al. (2006) Enhanced expression of hypersensitive alpha4* nAChR in adult mice increases the loss of midbrain dopaminergic neurons. FASEB J 20:935-46
Kovoor, Abraham; Seyffarth, Petra; Ebert, Jana et al. (2005) D2 dopamine receptors colocalize regulator of G-protein signaling 9-2 (RGS9-2) via the RGS9 DEP domain, and RGS9 knock-out mice develop dyskinesias associated with dopamine pathways. J Neurosci 25:2157-65
Chiu, Chi-Sung; Brickley, Stephen; Jensen, Kimmo et al. (2005) GABA transporter deficiency causes tremor, ataxia, nervousness, and increased GABA-induced tonic conductance in cerebellum. J Neurosci 25:3234-45
Vazquez, Luis E; Chen, Hong-Jung; Sokolova, Irina et al. (2004) SynGAP regulates spine formation. J Neurosci 24:8862-72
Orb, Sabine; Wieacker, Johannes; Labarca, Cesar et al. (2004) Knockin mice with Leu9'Ser alpha4-nicotinic receptors: substantia nigra dopaminergic neurons are hypersensitive to agonist and lost postnatally. Physiol Genomics 18:299-307
Fonck, Carlos; Nashmi, Raad; Deshpande, Purnima et al. (2003) Increased sensitivity to agonist-induced seizures, straub tail, and hippocampal theta rhythm in knock-in mice carrying hypersensitive alpha 4 nicotinic receptors. J Neurosci 23:2582-90
Jensen, Kimmo; Chiu, Chi-Sung; Sokolova, Irina et al. (2003) GABA transporter-1 (GAT1)-deficient mice: differential tonic activation of GABAA versus GABAB receptors in the hippocampus. J Neurophysiol 90:2690-701
Yu, Tzu-Ping; Lester, Henry A; Davidson, Norman (2003) Requirement of a critical period of GABAergic receptor blockade for induction of a cAMP-mediated long-term depression at CA3-CA1 synapses. Synapse 49:12-9
Slimko, Eric M; Lester, Henry A (2003) Codon optimization of Caenorhabditis elegans GluCl ion channel genes for mammalian cells dramatically improves expression levels. J Neurosci Methods 124:75-81

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