title: Glycine receptor deficiency and its effect on the horizontal vestibulo-ocular reflex: a study on the SPD1J mouse.
abstract: Inhibition is critical in the pathways controlling the vestibulo-ocular reflex (VOR) and plays a central role in the precision, accuracy and speed of this important vestibular-mediated compensatory eye movement. While γ-aminobutyric acid is the common fast inhibitory neurotransmitter in most of the VOR microcircuits, glycine is also found in key elements. For example, the omnidirectional pause neurons (OPNs) and inhibitory burst neurons in the horizontal VOR both use glycine as their preferred inhibitory neurotransmitter. Determining the precise contribution of glycine to the VOR pathway has been difficult due to the lack of selective tools; however, we used spasmodic mice that have a naturally occurring defect in the glycine receptor (GlyR) that reduces glycinergic transmission. Using this animal model, we compared the horizontal VOR in affected animals with unaffected controls. Our data showed that initial latency and initial peak velocity as well as slow-phase eye movements were unaffected by reduced glycinergic transmission. Importantly however, there were significant effects on quick-phase activity, substantially reducing their number (30-70 %), amplitude (~55 %) and peak velocity (~38 %). We suggest that the OPNs were primarily responsible for the reduced quick-phase properties, since they are part of an unmodifiable, or more 'hard-wired', microcircuit. In contrast, the effects of reduced glycinergic transmission on slow-phases were likely ameliorated by the intrinsically modifiable nature of this pathway. Our results also suggested there is a 'threshold' in GlyR-affected animals, below which the effects of reduced glycinergic transmission were undetected.
authors.affiliation: Balance and Vision Laboratory, Neuroscience Research Australia, Cnr Barker Street & Easy Street, Randwick, Australia.
authors.forename: Patrick P
authors.initials: PP
authors.lastname: Hübner
authors.forename: Rebecca
authors.initials: R
authors.lastname: Lim
authors.forename: Alan M
authors.initials: AM
authors.lastname: Brichta
authors.forename: Americo A
authors.initials: AA
authors.lastname: Migliaccio
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D015536:Down-Regulation / Q000502:physiology; D005133:Eye Movements / Q000235:genetics* / Q000502:physiology*; D005260:Female; D005998:Glycine / Q000502:physiology; D006579:Heterozygote; D006720:Homozygote; D008297:Male; D051379:Mice; D008817:Mice, Mutant Strains; D018009:Receptors, Glycine / Q000172:deficiency* / Q000235:genetics / Q000502:physiology; D012027:Reflex, Vestibulo-Ocular / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology*; D013997:Time Factors; D005680:gamma-Aminobutyric Acid / Q000502:physiology
chemical_list: D018009:Receptors, Glycine; D005680:gamma-Aminobutyric Acid; D005998:Glycine