GABAergic neurons in the lateral superior olive of the hamster are distinguished by differential expression of gad isoforms during development

Abstract

γ-Aminobutyric acid (GABA) is an inhibitory neurotransmitter that is synthesized by two isoforms of glutamic acid decarboxylase (GAD), GAD65 and GAD67. Using in situ hybridization and immunocytochemical techniques in hamsters, we investigated the postnatal development of GAD isoforms within the lateral superior olive (LSO) where GABAergic neurons form part of a descending efferent projection to the cochlea. In the neonatal hamster LSO, GAD67 immunoreactivity, GAD67 transcript labeling, and intense GABA immunostaining are at low levels. However, robust GAD65 mRNA expression is found throughout the LSO during the early postnatal period. The neonatal GABAergic expression patterns are in stark contrast to the adult where the LSO has robust GAD67 mRNA expression and weak GAD65 mRNA expression. Cells exhibiting intense GABA immunolabeling were also found in the same LSO locations as robust GAD67 mRNA expression and intense GAD67 immunoreactivity. Additionally, GAD67-positive cells in the LSO were retrogradely labeled from the cochlea confirming that these cells are a part of the lateral olivocochlear system. The late onset of GAD67 expression and intense GABA immunoreactivity in LSO neurons are consistent with the relatively late maturation of the lateral olivocochlear neurons inferred from previous studies. During development, these data lead us to conclude that the GABAergic portion of the lateral olivocochlear system is distinguished by preferential GAD67 expression, intense GABA immunoreactivity, and relatively late postnatal onset.