Abstract

The synaptic regulation of pyramldal cell excitability will be examined in the hippocampal slice preparation. Two approaches will be used. The characteristics of the acidic amino acid receptors present on pyramidal cells will be determined with quantitative pharmacological methods. Intracellular recordings will be obtained from pyramidal cells, and dose response curves to receptor agonists will be constructed before and after perfusion with known concentrations of antagonists. The data will be analyzed by the Schild method. The results of these experiments should allow us to choose appropriate concentrations of antagonists for selective blockage of certain acidic amino acid receptors. This information will be used in an attempt to identify the receptor(s) underlying the epileptiform burst response and the Schaffer-commissural EPSP in the CAl region. Intrad endritic recordings will be made from pyramidal cells in order to study a form of non-hyperpolarizing dendritic inhibition. Paired pulse experiments will be done to determine if conductance shunting is a prominant mechanism for dendritic inhibition. The data should allow a better understanding of the functional consequences of integration of excitatory and inhibitory synaptic potentials in pyramidal cell dendrites.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
5R01NS022249-03
Application #
3404441
Study Section
Neurological Sciences Subcommittee 1 (NLS)
Project Start
1985-09-01
Project End
1988-08-31
Budget Start
1987-09-01
Budget End
1988-08-31
Support Year
3
Fiscal Year
1987
Total Cost
Indirect Cost

  Institution

Name
University of North Carolina Chapel Hill
Department
Type
Schools of Medicine
DUNS #
078861598
City
Chapel Hill
State
NC
Country
United States
Zip Code
27599

  Publications

Verdoorn, T A; Kleckner, N W; Dingledine, R (1989) N-methyl-D-aspartate/glycine and quisqualate/kainate receptors expressed in Xenopus oocytes: antagonist pharmacology. Mol Pharmacol 35:360-8
Dingledine, R; Boland, L M; Chamberlin, N L et al. (1988) Amino acid receptors and uptake systems in the mammalian central nervous system. Crit Rev Neurobiol 4:1-96
Kleckner, N W; Dingledine, R (1988) Requirement for glycine in activation of NMDA-receptors expressed in Xenopus oocytes. Science 241:835-7
Berry, B W; Boland, L M; Hoch, D B et al. (1988) L-glutamate binding site on N18-RE-105 neuroblastoma hybrid cells is not coupled to an ion channel. J Neurochem 51:1176-83
Verdoorn, T A; Dingledine, R (1988) Excitatory amino acid receptors expressed in Xenopus oocytes: agonist pharmacology. Mol Pharmacol 34:298-307
Verdoorn, T A; Kleckner, N W; Dingledine, R (1987) Rat brain N-methyl-D-aspartate receptors expressed in Xenopus oocytes. Science 238:1114-6
Dingledine, R; Roth, A A; King, G L (1987) Synaptic control of pyramidal cell activation in the hippocampal slice preparation in the rat. Neuroscience 22:553-61
Korn, S J; Giacchino, J L; Chamberlin, N L et al. (1987) Epileptiform burst activity induced by potassium in the hippocampus and its regulation by GABA-mediated inhibition. J Neurophysiol 57:325-40
Dingledine, R; Hynes, M A; King, G L (1986) Involvement of N-methyl-D-aspartate receptors in epileptiform bursting in the rat hippocampal slice. J Physiol 380:175-89