Cellular distribution of d-serine, serine racemase and d-amino acid oxidase in the rat vestibular sensory epithelia

Glutamate is the main neurotransmitter at the synapses between sensory cells and primary afferents in the peripheral vestibular system. Evidence has recently been obtained demonstrating that the atypical amino acid d-serine is the main endogenous co-agonist of the N-methyl-d-aspartate receptors in the CNS. We studied the distribution of d-serine and its synthesizing and degrading enzymes, serine racemase and d-amino acid oxidase in the rat vestibular sensory epithelium using immunocytochemistry. d-Serine, serine racemase and d-amino acid oxidase were localized in the transitional cells, which are parasensory cells located between the sensory epithelium and the dark cells. The dark cells expressed only serine racemase. d-Serine was also detected in the supporting cells of the sensory epithelium. These cells, which are in close contact with glutamatergic synapses, express GLAST, a glial specific transporter for glutamate. They may have similar functions to glial cells in the CNS and thus expression of d-serine suggests a neuromodulator role for d-serine at the glutamatergic synapses in the peripheral vestibular system. Our data also indicate that the metabolism of d-serine is not restricted to glial cells suggesting that the amino acid may play an additional role in the peripheral nervous system

A quantitative survey of gravity receptor function in mutant mouse strains.

The purpose of this research was to identify vestibular deficits in mice using linear vestibular evoked potentials (VsEPs). VsEP thresholds, peak latencies, and peak amplitudes from 24 strains with known genetic mutations and 6 inbred background strains were analyzed and descriptive statistics generated for each strain. Response parameters from mutant homozygotes were compared with heterozygote and/or background controls and all strain averages were contrasted to normative ranges. Homozygotes of the following recessive mutations had absent VsEPs at the ages tested: Espn(je), Atp2b2dfw-2J, Spnb4qv-lnd2J, Spnb4qv-3J, Myo7ash1, Tmie(sr), Myo6sv, jc, Pcdh15av-J, Pcdh15av-2J, Pcdh15av-3J, Cdh23v-2J, Sans(js), hr, Kcne1pkr and Pou3f4del. These results suggest profound gravity receptor deficits for these homozygotes, which is consistent with the structural deficits that have been documented for many of these strains. Homozygotes of Catna2cdf, Grid2ho4J, Wnt1sw, qk, and Mbpshi strains and heterozygotes of Grid2lc had measurable VsEPs but one or more response parameters differed from the respective control group (heterozygote or background strain) or were outside normal ranges. For example, qk and Mbpshi homozygotes showed significantly prolonged latencies consistent with the abnormal myelin that has been described for these strains. Prolonged latencies may suggest deficits in neural conduction; elevated thresholds suggest reduced sensitivity, and reduced amplitudes may be suggestive for reduced neural synchrony. One mutation, Otx1jv, had all VsEP response parameters within normal limits--an expected finding because the abnormality in Otxljv is presumably restricted to the lateral semicircular canal. Interestingly, some heterozygote groups also showed abnormalities in one or more VsEP response parameters, suggesting that vestibular dysfunction, although less severe, may be present in some heterozygous animals