Abstracts

RATIONALE: Increasing evidence from epileptic brain regions such as the cerebral cortex and hippocampus has implicated nitric oxide (NO) as neuroprotective. Since blockade of NO generation increases N-Methyl-D-Aspartate (NMDA) receptor function, NO may also be anticonvulsive. Absence oscillations (3-4Hz) have been strongly linked with thalamocortical dysrhythmia, which is characterized by abnormality in neural information flow through thalamocortical loops. Because these loops depend in part upon excitatory neurotransmission via NMDA receptors, we have examined the role of NO in glutamatergic neurotransmission in the thalamus. METHODS: We tested the hypothesis that NO suppresses NMDA receptor function with an in vitro thalamic slice preparation, using both rat and ferret models. Ferret thalamic slices that contain the lateral geniculate nucleus (LGN) and thalamic reticular nucleus are of particular interest because they are capable of generating 3-4Hz paroxysmal activity. Excitatory post synaptic potentials (EPSPs) in the LGN were elicited upon stimulating the optic tract. Recordings were made in current clamp mode. NO donor compounds were bath applied (2-5mM), and the EPSP measures were repeated. The NO donors included SNAP and NOC-18; Alexis Corporation. RESULTS: The NO donors selectively and markedly attenuated the NMDA receptor component of the EPSP, as verified with the NMDA receptor antagonist DL-2-Amino-5-Phosphono-Valeric Acid, APV. The time to 1/e of the peak amplitude of the EPSP was reduced by 52%. There was no apparent effect on the peak amplitude of the early component, but its rising slope was increased by 22%. Application of spent donor or ACSF had no effect. CONCLUSIONS: Our data suggest that Nitric Oxide may serve its neuroprotective and anticonvulsive roles through selective inhibition of the NMDA receptor, and attenuation of calcium influx through this route.