Localization of rat glycine receptor α1 and α2 subunit transcripts in the developing auditory brainstem

Abstract

Glycine receptors (GlyRs), aside from GABA(A) receptors, mediate fast postsynaptic inhibition in the mammalian nervous system. Spatial and temporal expression of the genes encoding ligand-binding alpha subunits (alpha1-alpha4) and the structural beta subunit leads to the formation of various GlyR isoforms. Currently, the idea of the GlyRs containing the "adult" alpha1 subunit replacing those with the "neonatal" alpha2 subunit during early postnatal development predominates. Here, we describe the patterns of expression of the GlyR alpha1 and alpha2 subunit genes in the rat auditory brainstem between postnatal day (P) 0 and P20, by using both nonradioactive and radioactive in situ hybridization. We show that the alpha1 subunit mRNA appears throughout the auditory brainstem during the first 8 postnatal days, which resembles the time of onset described within the spinal cord. In the rostral auditory nuclei (nuclei of the lateral lemniscus and inferior colliculus), the alpha1 subunit transcript appears later (P8) than in the caudal nuclei (cochlear nuclear complex and superior olivary complex; P0). Surprisingly, we found that low levels of the alpha2 subunit transcript are present in the auditory brainstem at birth and persist throughout the period analyzed. However, alpha2 subunit mRNA is present at high levels in other neonatal brainstem structures, such as cranial motor nuclei. Therefore, we conclude that the changes in GlyR composition in the auditory brainstem deviate from the classic alpha2 to alpha1 subunit switch observed in spinal cord. Our data suggest that genes for other GlyR subunits (e.g., alpha3 and alpha4) may be expressed during early development in the auditory brainstem.

Target-Specific IPSC Kinetics Promote Temporal Processing in Auditory Parallel Pathways

“…The trend is not always true in all neural circuits (Lynch, 2009). Our study suggests that such a switch might occur in T-stellate cells during development and might not occur in bushy cells, which would be consistent with the continued presence of α 2 mRNA in the AVCN through adulthood (Piechotta et al, 2001). …”

Differential distribution of synaptic endings containing glutamate, glycine, and GABA in the rat dorsal cochlear nucleus

“…The ␤ subunit is not necessary for forming a functional channel . In the DCN, mRNA studies have shown the presence of the ␣2 subunit only early during development (Sato et al, 2000;Piechotta et al, 2001) and ␣1, ␣3, and ␤ in the adult rat (Sato et al, 2000;Piechotta et al, 2001). At the protein level, the existence of the glycinergic input was previously analyzed by using an antibody against the glycine receptorassociated protein, gephyrin, as an indicator of GlyRs in the cochlear nucleus.…”

Glycine receptor mutants of the mouse: what are possible routes of inhibitory compensation?

“…The resulting proteins differ in only two amino acid residues in the extracellular N-terminal part of the receptor (Kuhse et al, 1991). Recent findings suggest that the α2 expression persists into adulthood in retina, cerebellum, and auditory brain stem (Piechotta et al, 2001; Young and Cepko, 2004; Heinze et al, 2007; Nobles et al, 2012). GlyR3α also exists in two splice variants, differing in a 15 amino acid insertion in the TM3-4 loop (α3L and α3K).…”