Abstract
BackgroundIn the mammalian superior olivary complex (SOC), synaptic inhibition contributes to the processing of binaural sound cues important for sound localization. Previous analyses demonstrated a tonotopic gradient for postsynaptic proteins mediating inhibitory neurotransmission in the lateral superior olive (LSO), a major nucleus of the SOC. To probe, whether a presynaptic molecular gradient exists as well, we investigated immunoreactivity against the vesicular inhibitory amino acid transporter (VIAAT) in the mouse auditory brainstem.ResultsImmunoreactivity against VIAAT revealed a gradient in the LSO and the superior paraolivary nucleus (SPN) of NMRI mice, with high expression in the lateral, low frequency processing limb and low expression in the medial, high frequency processing limb of both nuclei. This orientation is opposite to the previously reported gradient of glycine receptors in the LSO. Other nuclei of the SOC showed a uniform distribution of VIAAT-immunoreactivity. No gradient was observed for the glycine transporter GlyT2 and the neuronal protein NeuN. Formation of the VIAAT gradient was developmentally regulated and occurred around hearing-onset between postnatal days 8 and 16. Congenital deaf Claudin14−/− mice bred on an NMRI background showed a uniform VIAAT-immunoreactivity in the LSO, whereas cochlear ablation in NMRI mice after hearing-onset did not affect the gradient. Additional analysis of C57Bl6/J, 129/SvJ and CBA/J mice revealed a strain-specific formation of the gradient.ConclusionsOur results identify an activity-regulated gradient of VIAAT in the SOC of NRMI mice. Its absence in other mouse strains adds a novel layer of strain-specific features in the auditory system, i.e. tonotopic organization of molecular gradients. This calls for caution when comparing data from different mouse strains frequently used in studies involving transgenic animals. The presence of strain-specific differences offers the possibility of genetic mapping to identify molecular factors involved in activity-dependent developmental processes in the auditory system. This would provide an important step forward concerning improved auditory rehabilitation in cases of congenital deafness.
Highlights
In the mammalian superior olivary complex (SOC), synaptic inhibition contributes to the processing of binaural sound cues important for sound localization
In the SOC of P30 NMRI mice, vesicular inhibitory amino acid transporter (VIAAT)-ir showed a strong gradient across the lateral superior olive (LSO) with considerably higher immunoreactivity in the lateral limb of this nucleus (Fig. 2A a, a′)
Quantification of VIAAT-boutons in a Region of interest (ROI) of 70 × 70 μm revealed no difference in bouton abundancy (Fig. 3B; medial: 1392 ± 259, lateral: 1415 ± 204; p = 0.878), indicating a stronger VIAAT expression in synaptic boutons of the lateral limb
Summary
In the mammalian superior olivary complex (SOC), synaptic inhibition contributes to the processing of binaural sound cues important for sound localization. During the analysis of various transgenic mouse models [9,10,11,12], we observed occasionally a gradient in immunoreactivity against the vesicular inhibitory amino acid transporter VIAAT ( known as VGAT) in the LSO. This protein serves as an ideal marker for inhibitory synapses, as it is the only transporter filling synaptic vesicles with the inhibitory neurotransmitters glycine and GABA [13,14,15].
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