Abstract

This work will be complementary to patch-clamp recordings of amino acid- activated single channel currents in outside-out patches excised from neurons in brain slices in comparison to amino acid-activated single channel currents in outside-out patches excised from cell in culture transiently transfected with specific subunits of excitatory amino acid receptors, thereby expressing only special recombinant receptor. I also propose to study long-term changes of excitatory synapses during normal and experimentally modified development in neurons of rat primary visual cortex. Finally, in light of experimental evidence for a role of neurotrophic factors underlying the plasticity of synaptic connections during development of the visual system, I will also study the effects of endogenously provided neurotrophins on AA-mediated synapses during normal development and during visual deprivation. Data obtained from these specific aims will permit the relative contributions of variations in the molecular forms of excitatory amino acid receptors to be distinguished as determinants of synaptic functions that underlie behavior and that are relevant in various CNS disorders.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Modified Research Career Development Award (K04)
Project #
5K04NS001680-02
Application #
2259745
Study Section
Neurological Sciences Subcommittee 1 (NLS)
Project Start
1993-12-01
Project End
1998-11-30
Budget Start
1994-12-01
Budget End
1995-11-30
Support Year
2
Fiscal Year
1995
Total Cost
Indirect Cost

  Institution

Name
Georgetown University
Department
Physiology
Type
Schools of Dentistry
DUNS #
049515844
City
Washington
State
DC
Country
United States
Zip Code
20057

  Publications

Vicini, S (1999) New perspectives in the functional role of GABA(A) channel heterogeneity. Mol Neurobiol 19:97-110
Vicini, S; Wang, J F; Li, J H et al. (1998) Functional and pharmacological differences between recombinant N-methyl-D-aspartate receptors. J Neurophysiol 79:555-66
Stocca, G; Vicini, S (1998) Increased contribution of NR2A subunit to synaptic NMDA receptors in developing rat cortical neurons. J Physiol 507 ( Pt 1):13-24
Corsi, L; Li, J H; Krueger, K E et al. (1998) Up-regulation of NR2B subunit of NMDA receptors in cerebellar granule neurons by Ca2+/calmodulin kinase inhibitor KN93. J Neurochem 70:1898-906
Grayson, D R; Zhu, W; Harris, B T et al. (1998) Differentially expressed GABAA-receptor subunits result in structurally and functionally receptor assemblies following excitatory afferent synaptic transmission. Perspect Dev Neurobiol 5:193-205
Li, J H; Wang, Y H; Wolfe, B B et al. (1998) Developmental changes in localization of NMDA receptor subunits in primary cultures of cortical neurons. Eur J Neurosci 10:1704-15
Wang, X H; Zhu, W J; Corsi, L et al. (1998) Chronic dizocilpine (MK-801) reversibly delays GABA(A) receptor maturation in cerebellar granule neurons in vitro. J Neurochem 71:693-704
Zhu, W J; Wang, J F; Corsi, L et al. (1998) Lanthanum-mediated modification of GABAA receptor deactivation, desensitization and inhibitory synaptic currents in rat cerebellar neurons. J Physiol 511 ( Pt 3):647-61
Carmignoto, G; Pizzorusso, T; Tia, S et al. (1997) Brain-derived neurotrophic factor and nerve growth factor potentiate excitatory synaptic transmission in the rat visual cortex. J Physiol 498 ( Pt 1):153-64
Zhu, W J; Vicini, S (1997) Neurosteroid prolongs GABAA channel deactivation by altering kinetics of desensitized states. J Neurosci 17:4022-31

Showing the most recent 10 out of 16 publications