Modulation of inhibitory and excitatory synaptic transmission in rat inferior colliculus after unilateral cochleectomy: An in situ and immunofluorescence study

Abstract

We investigated whether inhibitory synaptic transmission mediated through glycinergic receptor, GABA A receptors, glutamic acid decarboxylase, the enzyme synthesizing GABA, and excitatory synaptic transmission through α-amino-3-hydroxi-5-methylisoxazole-4-propionic acid receptors and N-methyl- d-aspartate receptors are affected in the inferior colliculus by unilateral surgical cochleectomy. In situ hybridization and immunohistofluorescence studies were performed in normal and lesioned adult rats at various times following the lesion (1–150 days). Unilateral auditory deprivation decreased glycine receptor α1 and glutamic acid decarboxylase 67 expression in the contralateral central nucleus of the inferior colliculus. This decrease began one day after cochleectomy, and continued until day 8; thereafter expression was consistently low until day 150. The glycine receptor α1 subunit decrease did not occur if a second contralateral cochleectomy was performed either on day 8 or 150 after the first cochleectomy. Bilateral cochleectomy caused also a bilateral inferior colliculus diminution of glutamic acid decarboxylase 67 mRNA at post-lesion day 8 but there were no changes in glycine receptor α1 compared with controls. In contrast, the abundance of other α2–3, and β glycine receptor, gephyrin, the anchoring protein of glycine receptor, the α1, β2 and γ2 subunits of GABA A receptors, GluR2, R3 subunits of α-amino-3-hydroxi-5-methylisoxazole-4-propionic acid receptors, and NR1 and NR2A transcripts of N-methyl- d-aspartate receptors was unaffected during the first week following the lesion. Thus, unilateral cochlear removal resulted in a selective and long-term decrease in the amount of the glycine receptor α1 subunit and of glutamic acid decarboxylase 67 in the contralateral central nucleus of the inferior colliculus. These changes most probably result from the induced asymmetry of excitatory auditory inputs into the central nucleus of the inferior colliculus and may be one of the mechanisms involved in the tinnitus frequently encountered in patients suffering from a sudden hearing loss.