Hypoxia-Induced Long-Term Potentiation in the Vestibular Nucleus.

Abstract

Transient ischemia due to a decrease in vertebrobasilar insufficiency (VBI) induces the hypoxia of vestibular nucleus (VN) and frequently cause vertigo. Furthermore, it is occasionally experienced that dizziness continues in the long term after strong rotatory vertigo in VBI. Since glutamate is thought to play an important role in the neurotransmission of VN, this study was undertaken to examine the effect of hypoxia on the VN neuron and the role of the glutamate in the hypoxia induced neuronal activities using electrophysiological and microiontophoretic technique. Cats anesthetized with α-chloralose were ventilated with a respirator. A silver recording microelectrode was inserted into the VN and the spontaneous firing of the neurons was continuously recorded on an ink-writing recorder through a spike counter. Micropipettes attached along the microelectrode were used for microiontophoretic application of 6,7-Dinitroquinoxaline-2,3-dione (DNQX), non-NMDA receptor antagonist and (+) 5-methyl-l0,l1-dihydro-5H-dibenzo(a,d) cyclohepten- 5,10-imine (MK801), NMDA receptor antagonist. The spontaneous firing in VN neurons increased transiently and then decreased, resulting in the disappearance in firings during 3 minutes inhalation of 5%O2. However, the firings appeared again and persistently increased after the cessation of 5%O2. Transient increase of the firing during hypoxia and persistent increase after the cessation of hypoxia were herein termed Hypoxic Depolarization (HD) and Post Hypoxic Potentiation (PHP), respectively. HD was significantly (P<0.01) suppressed by DNQX and MK801. Since HD was suppressed by glutamate receptor antagonist, HD was assumed to be caused by excessive glutamate released from presynaptic terminals in the VN neurons. HD correlated significantly with PHP (R=0.609, p<0.01). We indicate that enhancement of PHP was the change of glutamate receptor-mediated synaptic plasticity caused by HD in the VN neurons. In conclusion, it is suggested that HD and PHP shown in this electrophysiological study might imply possible mechanism underlying the onset of acute vertigo and persistent dizziness in VBI.