Glutamatergic transmission of neuronal responses to carbachol in rat dorsal cochlear nucleus slices

Abstract

This study found that glutamate receptor antagonists block the excitatory effects of carbachol, a cholinergic agonist, on bursting neurons in the dorsal cochlear nucleus of rat brain slices. Among antagonists for glutamate receptor subtypes, those for non- N-methyl- d-aspartate ionotropic glutamate receptors were more potent than those for N-methyl- d-aspartate receptors. The glutamate receptor antagonists did not block the effects of carbachol on regularly firing neurons in the dorsal cochlear nucleus of the same slices. Antagonists for GABA or glycine receptors did not alter the effects of carbachol on bursting neurons. Effects of carbachol on bursting activity could be mimicked by application of glutamate or its agonist, α-amino-3-hydroxy-5-methylisoxazole-4-propionate, whose effects were not blocked by synaptic blockade. During carbachol application, increased release of glutamate and glycine from the dorsal cochlear nucleus part of brain slices was measured using high-performance liquid chromatography. Release of other amino acids showed no significant change. The results suggest that, in rat dorsal cochlear nucleus, cholinergic effects on regular and bursting spontaneous firing occur through different mechanisms. Cholinergic effects on regular neurons (which include fusiform cells) are direct, through muscarinic receptors. Cholinergic effects on bursting neurons (which include cartwheel cells) are indirect and involve glutamatergic neurotransmission, mostly via non- N-methyl- d-aspartate ionotropic receptors. The granule cell–parallel fiber pathway may be involved in this glutamatergic transmission.