Altered inhibitory synaptic transmission in superficial dorsal horn neurones in spastic and oscillator mice.
The spastic (spa) and oscillator (ot) mouse have naturally occurring mutations in the inhibitory glycine receptor (GlyR) and exhibit severe motor disturbances when exposed to unexpected sensory stimuli. We examined the effects of the spa and ot mutations on GlyR- and GABAAR-mediated synaptic transmission in the superficial dorsal horn (SFDH), a spinal cord region where inhibition is important for nociceptive processing. Spontaneous mIPSCs were recorded from visually identified neurones in parasagittal spinal cord slices. Neurones received exclusively GABAAR-mediated mIPSCs, exclusively GlyR-mediated mIPSCs or both types of mIPSCs. In control mice (wild-type and spa/+) over 40% of neurones received both types of mIPSCs, over 30% received solely GABAAR-mediated mIPSCs and the remainder received solely GlyR-mediated mIPSCs. In spa/spa animals, 97% of the neurones received exclusively GABAAergic or both types of mIPSCs. In ot/ot animals, over 80 % of the neurones received exclusively GABAAR-mediated mIPSCs. GlyR-mediated mIPSC amplitude and charge were reduced in spa/spa and ot/ot animals. GABAAR-mediated mIPSC amplitude and charge were elevated in spa/spa but unaltered in ot/ot animals. GlyR- and GABAAR-mediated mIPSC decay times were similar for all genotypes, consistent with the mutations altering receptor numbers but not kinetics. These findings suggest the spastic and oscillator mutations, traditionally considered motor disturbances, also disrupt inhibition in a sensory region associated with nociceptive transmission. Furthermore, the spastic mutation results in a compensatory increase in GABAAergic transmission in SFDH neurones, a form of inhibitory synaptic plasticity absent in the oscillator mouse.
Graham
B A
BA
School of Biomedical Sciences, Faculty of Health, The University of Newcastle, Callaghan, NSW 2308, Australia.
Schofield
P R
PR
Sah
P
P
Callister
R J
RJ
D000818:Animals; D005260:Female; D005838:Genotype; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008818:Mice, Neurologic Mutants; D009128:Muscle Spasticity / Q000503:physiopathology*; D009433:Neural Inhibition / Q000502:physiology*; D018408:Patch-Clamp Techniques; D020671:Posterior Horn Cells / Q000502:physiology*; D011963:Receptors, GABA-A / Q000502:physiology; D018009:Receptors, Glycine / Q000235:genetics* / Q000502:physiology; D009435:Synaptic Transmission / Q000502:physiology*
D011963:Receptors, GABA-A; D018009:Receptors, Glycine