NORADRENERGIC MODULATION OF NEURONAL RESPONSES TO N-METHYL-d-ASPARTATE IN THE VESTIBULAR NUCLEI: AN ELECTROPHYSIOLOGICAL AND IMMUNOHISTOCHEMICAL STUDY

摘要

Excitatory responses evoked by N-methyl-D-aspartate (NMDA) in the vestibular nuclei (VN) of the rat were studied in vivo during microiontophoretic application of noradrenaline (NA) and/or its agonists and antagonists. Ejection of NA-modified excitatory responses mediated by NMDA receptors (NMDAR) in all neurons tested; the effect was enhancement in 59% of cases and depression in the remaining 41%. Enhancements prevailed in all VN with the exception of the lateral vestibular nucleus, where both effects were recorded in an equal number of cases. The enhancing action of NA on NMDAR-mediated responses was mimicked by the noradrenergic beta-receptor agonist isoproterenol, the beta_1 specific agonist denopamine and the alpha_2 agonist clonidine. These effects were blocked respectively by the generic beta-receptor antagonist timolol, the beta_1 antagonist atenolol and the alpha_2 antagonist yohimbine. In contrast, application of the alpha_1 receptor agonist cirazoline and the specific alpha_1 antagonist prazo-sin respectively mimicked and partially antagonized the depression of NMDAR-mediated excitations induced by NA. Double-labeling immunohistochemical techniques demonstrated broad colocalization of NMDAR (specifically NR1 and NR2 subunits) with noradrenergic receptors (alpha_1, alpha_2 and beta_1) in many VN neurons; only minor differences were found between nuclei. These results indicate that NA can produce generalized modulation of NMDAR-mediated excitatory neurotransmission in VN, which may in turn modify synaptic plasticity within the nuclei.