Altered inhibitory synaptic transmission in superficial dorsal horn neurones in spastic and oscillator mice
Copyright policy )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.
- University of Queensland Australia
- University of Newcastle Australia Australia
- Australian National University Australia
- University of Queensland Australia
- Garvan Institute of Medical Research Australia
Male, 571, Patch-Clamp Techniques, Genotype, Physiology, genotype, oscillator mouse, animal cell, GABAergic transmission, Synaptic Transmission, Evoked Allodynia, animal tissue, Central-nervous-system, Mice, Mice, Neurologic Mutants, Receptors, Glycine, male, spastic mouse, inhibition kinetics, Slice Preparation, Animals, controlled study, gene mutation, Frameshift Mutation, Brain-stem Motoneurons, superficial dorsal horn, Gabaergic Synapses, spinal cord, Neural Inhibition, Glycine-receptor, Receptors, GABA-A, Receptor Alpha-1 Subunit, Gaba(a) Receptors, Mice, Inbred C57BL, Posterior Horn Cells, female, exposure, Muscle Spasticity, motor dysfun, Keywords: 4 aminobutyric acid A receptor, disease severity, Female, Rat Spinal-cord, inhibitory postsynaptic potential, glycine receptor
Male, 571, Patch-Clamp Techniques, Genotype, Physiology, genotype, oscillator mouse, animal cell, GABAergic transmission, Synaptic Transmission, Evoked Allodynia, animal tissue, Central-nervous-system, Mice, Mice, Neurologic Mutants, Receptors, Glycine, male, spastic mouse, inhibition kinetics, Slice Preparation, Animals, controlled study, gene mutation, Frameshift Mutation, Brain-stem Motoneurons, superficial dorsal horn, Gabaergic Synapses, spinal cord, Neural Inhibition, Glycine-receptor, Receptors, GABA-A, Receptor Alpha-1 Subunit, Gaba(a) Receptors, Mice, Inbred C57BL, Posterior Horn Cells, female, exposure, Muscle Spasticity, motor dysfun, Keywords: 4 aminobutyric acid A receptor, disease severity, Female, Rat Spinal-cord, inhibitory postsynaptic potential, glycine receptor
citations This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).54 popularity This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.Top 10% influence This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).Top 10% impulse This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.Top 10%
Citations provided by BIP!Popularity provided by BIP!