Immunohistochemical Localization of Glycine Receptor (alpha1+alpha2) in the Auditory Brain Stem of Circling Mouse / 대한해부학회지

Hearing loss in adults can stem from damage to the cochlea and the cochlear nerves inflicted by intense noise, mechanical trauma, or disease. Hearing loss is associated with degenerative changes in central auditory pathways, and hearing deficits are often accompanied by changes in the synaptic organization of the central auditory pathways. In addition to structural rearrangements, hearing loss may induce changes in the strength of synaptic transmissions. These effects may alter both transient and persistent regulation of transmitter release from glutamatergic, glycinergic, and GABAergic pathways in the auditory brain stem. The converging excitatory and inhibitory inputs are exquisitely organized topographically and are aligned perfectly with each other. The LSO and MNTB in the mammalian auditory brain stem provide and receive many glycinergic inputs. Thus, this auditory system is a useful model to study inhibitory synaptic development. However, little is known about the inhibitory synapses in the central nervous system. First, we used immunohistochemistry to compare the glycine receptor (GlyR) distribution in the LSO and MNTB, which project glycinergic inhibitory input into the auditory brainstem, in circling mice (P16), which have a spontaneous mutation in the inner ear, with wild-type mice. The relative immunoreactive density of the LSO was 86.4+/-7.2 in wild-type, 76.7+/-10.7 in heterozygous, and 61.1+/-4.1 in homozygous mice. The relative immunoreactive density of the MNTB was 97.6+/-8.7 in wild-type, 91.7+/-8.9 in heterozygous, and 74.9+/-7.8 in homozygous mice. These results reveal a decreased GlyR immunoreactivity in both the LSO and MNTB, which may be attributable to a postsynaptic decrease in GlyR number. Our model uses congenitally deaf mice, in which both spontaneous and evoked auditory nerve activity are disrupted because of dysfunctional hair cell-spiral ganglion cell transmission. This provides a naturally occurring model that may provide valuable insights into the central aspects of human congenital deafness in addition to the central consequences of a lack of auditory nerve activity. Our results are likely to be relevant to our understanding of the central changes underlying human hereditary deafness.

Tetanus-induced LTD of Developing MNTB-LSO Synapses in Rat is Dependent on Postsynaptic Ca2+

Because synaptic refinement of medial nucleus of trapezoid body (MNTB) - lateral superior olive (LSO) synapses is most active during the first postnatal week and the long term depression (LTD) has been suggested as one of its mechanisms, LTD of MNTB-LSO synapses was investigated in neonatal rat brain stem slices with the whole cell voltage clamp technique. In Mg2+ free condition, tetanus (10 stimuli at 10 Hz for 2 min) in the current clamp mode induced a robust LTD of isolated D, L-APV-sensitive postsynaptic currents (PSCs) for more than 30 min (n=6, 2.4+/-0.4% of the control), while isolated CNQX-sensitive PSCs were not suppressed (n=6, 95.3+/-1.6%). Tetanus also elicited similar LTD in the isolated GABAergic/glycinergic PSCs (n=5, 3.6+/-0.5%) and mixed PSCs (GABAergic/glycinergic/glutamatergic) (n=4, 2.2+/-0.7%). However, such a strong LTD was not observed in the mixed PSCs when 10 mM EGTA was added in the internal solution (n=10), indicating that postsynaptic Ca2+ rise is needed for the strong LTD. This robust LTD might contribute to the active synaptic refinement occurring during the first postnatal week.