Development of adult-type inhibitory glycine receptors in the central auditory system of rats.

Abstract

Inhibitory synaptic activity is crucial for many aspects of acoustic information processing and mainly mediated by glycine and gamma-aminobutyric acid, the two principal inhibitory neurotransmitters in the auditory system. Glycine exerts its inhibitory action via binding to postsynaptic receptors existing in various isoforms. Here we have investigated the spatiotemporal distribution of adult-type, strychnine-sensitive glycine receptors (GlyRs) in the rat auditory system by using a specific antibody against the ligand-binding alpha1 GlyR subunit. In adults, alpha1 GlyRs were found at all relay stations of the auditory pathway except for the medial geniculate body and the auditory cortex. In most brainstem nuclei, labeling was characterized by dense clusters of heavily immunoreactive puncta outlining the somata and proximal dendrites, indicative of a powerful glycinergic inhibition. No alpha1 immunoreactivity was seen in the auditory system of fetal rats, consistent with results obtained by others in the spinal cord. At birth, labeling was weak and restricted to defined nuclei of the cochlear nuclear complex and the superior olivary complex. By postnatal day 8, labeling was seen in all brainstem nuclei. At the first appearance of immunoreactivity, alpha1 GlyRs were diffusely distributed on the neuronal surface, yet they became clustered with age, finally densely incrusting the somata and proximal dendrites between the 3rd and 4th postnatal week, when the mature pattern of immunoreactivity was established. We never observed an overexpression of alpha1 GlyRs or a transient appearance in areas that are devoid of the receptor in adults. The late formation of glycinergic synapses harboring the adult-type GlyRs in the auditory system, at a time when internuclear connections have already formed, indicates that alpha1 GlyRs do not participate in early synaptogenesis.