The long-term goal of these studies is to attain a more fundamental understanding of the functions of NMDA receptors in development, in the mature brain, and in neurological diseases. To this end we have designed complementary experiments with the Xenopus oocyte expression system and the hippocampal slice preparation to answer the following questions: Is the sensitivity of the NMDA receptor to glycine, Mg or MK-801 regulated at the transcription level during development or in different brain regions? Are NMDA and quisqualate/kainate receptors encoded by different size transcript ? Do multiple transcript size classes encode NMDA receptors? What structural features of ligands promote agonist, antagonist and partial agonist activit at the glycine site? What functions does the glycine site subserve in synaptic transmission mediated by NMDA receptors in the hippocampal slice? Does the ionic permeability of NMDA receptors expressed in oocytes differ from that of receptors in their native neuronal environment? Can NMDA receptor mRNA be identified in Northern blots with an oligonucleotide probe shown in our laboratory to arrest the translation of NMDA but not kainate receptors? Can this oligonucleotide (or other similar ones) be used to scre n existing cDNA libraries to identify subunits of the NMDA receptor? A combination of molecular biological and electrophysiological techniques wil be used to address these questions.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
7R01NS027452-04
Application #
3413723
Study Section
Neurology C Study Section (NEUC)
Project Start
1989-08-01
Project End
1994-07-31
Budget Start
1992-09-01
Budget End
1993-07-31
Support Year
4
Fiscal Year
1992
Total Cost
Indirect Cost
Name
Emory University
Department
Type
Schools of Medicine
DUNS #
042250712
City
Atlanta
State
GA
Country
United States
Zip Code
30322
Rojas, Asheebo; Dingledine, Raymond (2013) Ionotropic glutamate receptors: regulation by G-protein-coupled receptors. Mol Pharmacol 83:746-52
Rojas, Asheebo; Wetherington, Jonathon; Shaw, Renee et al. (2013) Activation of group I metabotropic glutamate receptors potentiates heteromeric kainate receptors. Mol Pharmacol 83:106-21
Cox, Brian; Han, Ji-Sheng; Dingledine, Ray (2013) Avram Goldstein: the founder of molecular pharmacology. Mol Pharmacol 83:720-2
Laezza, Fernanda; Dingledine, Raymond (2011) Induction and expression rules of synaptic plasticity in hippocampal interneurons. Neuropharmacology 60:720-9
Kawajiri, S; Dingledine, R (1993) Multiple structural determinants of voltage-dependent magnesium block in recombinant NMDA receptors. Neuropharmacology 32:1203-11
McBain, C; Dingledine, R (1992) Dual-component miniature excitatory synaptic currents in rat hippocampal CA3 pyramidal neurons. J Neurophysiol 68:16-27
Curras, M C; Dingledine, R (1992) Selectivity of amino acid transmitters acting at N-methyl-D-aspartate and amino-3-hydroxy-5-methyl-4-isoxazolepropionate receptors. Mol Pharmacol 41:520-6
Dingledine, R; Hume, R I; Heinemann, S F (1992) Structural determinants of barium permeation and rectification in non-NMDA glutamate receptor channels. J Neurosci 12:4080-7
Kleckner, N W; Dingledine, R (1991) Regulation of hippocampal NMDA receptors by magnesium and glycine during development. Brain Res Mol Brain Res 11:151-9
Dingledine, R; Myers, S J; Nicholas, R A (1990) Molecular biology of mammalian amino acid receptors. FASEB J 4:2636-45

Showing the most recent 10 out of 11 publications