The major goals for the coming year are to further define excitatory synaptic transmission in hippocampal cultures and to study the role of excitatory neurotransmission in mediating anoxic neuronal injury in the hippocampal slice.
Specific aims i nclude: 1. Determining whether newly developed blockers of excitatory amino acids, such as kynurenic acid, antagonize EPSP's in culture. 2. Determining the role of the kainate and N-methyl-D-aspartate receptors in neurotransmission, long term potentiation, and burst generation. 3. Studying pairs of synaptically connected neurons to determine whether any form of synaptic potentiation occurs in culture. 4. Injecting presynaptic neurons with various transmitter candidates to see whether the post-synaptic potentials can be increased. 5. Determining whether blockade of excitatory neurotransmission in hippocampal slices protects them from anoxic injury. These experiments will use cultures of dissociated rat hippocampal neurons and slices of rat hippocampus. Physiological recording will be done with standard electrodes and amplifiers, as well as patch clamp electrodes in special cases. The long term objectives of this project are to obtain a better understanding of the physiology and pharmacology of excitatory neurotransmission and relate this to human neurological diseases. There is convincing evidence that excitatory transmitters, probably amino acids, are responsible for hypoxic/ischemic neuronal injury, epileptic brain damage, and some hereditary degenerative neurological illnesses. Clearly, more information about excitatory transmitters will be required if the treatment of these human diseases is to proceed on a rational basis.
|Rothman, S M; Thurston, J H; Hauhart, R E et al. (1987) Ketamine protects hippocampal neurons from anoxia in vitro. Neuroscience 21:673-8
|Rothman, S M; Thurston, J H; Hauhart, R E (1987) Delayed neurotoxicity of excitatory amino acids in vitro. Neuroscience 22:471-80
|Clark, G D; Rothman, S M (1987) Blockade of excitatory amino acid receptors protects anoxic hippocampal slices. Neuroscience 21:665-71
|Rothman, S M; Olney, J W (1986) Glutamate and the pathophysiology of hypoxic--ischemic brain damage. Ann Neurol 19:105-11
|Rothman, S M; Samaie, M (1985) Physiology of excitatory synaptic transmission in cultures of dissociated rat hippocampus. J Neurophysiol 54:701-13
|Rothman, S M (1985) The neurotoxicity of excitatory amino acids is produced by passive chloride influx. J Neurosci 5:1483-9