title: Intrinsic and synaptic homeostatic plasticity in motoneurons from mice with glycine receptor mutations.
abstract: Inhibitory synaptic inputs to hypoglossal motoneurons (HMs) are important for modulating excitability in brainstem circuits. Here we ask whether reduced inhibition, as occurs in three murine mutants with distinct naturally occurring mutations in the glycine receptor (GlyR), leads to intrinsic and/or synaptic homeostatic plasticity. Whole cell recordings were obtained from HMs in transverse brainstem slices from wild-type (wt), spasmodic (spd), spastic (spa), and oscillator (ot) mice (C57Bl/6, approximately postnatal day 21). Passive and action potential (AP) properties in spd and ot HMs were similar to wt. In contrast, spa HMs had lower input resistances, more depolarized resting membrane potentials, higher rheobase currents, smaller AP amplitudes, and slower afterhyperpolarization current decay times. The excitability of HMs, assessed by "gain" in injected current/firing-frequency plots, was similar in all strains whereas the incidence of rebound spiking was increased in spd. The difference between recruitment and derecruitment current (i.e., ΔI) for AP discharge during ramp current injection was more negative in spa and ot. GABAA miniature inhibitory postsynaptic current (mIPSC) amplitude was increased in spa and ot but not spd, suggesting diminished glycinergic drive leads to compensatory adjustments in the other major fast inhibitory synaptic transmitter system in these mutants. Overall, our data suggest long-term reduction in glycinergic drive to HMs results in changes in intrinsic and synaptic properties that are consistent with homeostatic plasticity in spa and ot but not in spd. We propose such plasticity is an attempt to stabilize HM output, which succeeds in spa but fails in ot.
authors.affiliation: School of Biomedical Sciences and Pharmacy, Faculty of Health and Hunter Medical Research Institute, University of Newcastle, Callaghan, Australia;
authors.forename: M A
authors.initials: MA
authors.lastname: Tadros
authors.forename: K E
authors.initials: KE
authors.lastname: Farrell
authors.forename: P R
authors.initials: PR
authors.lastname: Schofield
authors.forename: A M
authors.initials: AM
authors.lastname: Brichta
authors.forename: B A
authors.initials: BA
authors.lastname: Graham
authors.forename: A J
authors.initials: AJ
authors.lastname: Fuglevand
authors.forename: R J
authors.initials: RJ
authors.lastname: Callister
mesh_terms: D000367:Age Factors; D000818:Animals; D000831:Animals, Newborn; D001933:Brain Stem / Q000166:cytology; D005260:Female; D018684:Glycine Agents / Q000494:pharmacology; D066298:In Vitro Techniques; D053444:Inhibitory Postsynaptic Potentials / Q000235:genetics; D008297:Male; D008564:Membrane Potentials / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009046:Motor Neurons / Q000502:physiology*; D009154:Mutation / Q000235:genetics*; D009433:Neural Inhibition / Q000187:drug effects / Q000235:genetics; D009473:Neuronal Plasticity / Q000187:drug effects / Q000235:genetics*; D018408:Patch-Clamp Techniques; D018009:Receptors, Glycine / Q000235:genetics*; D013569:Synapses / Q000235:genetics*
chemical_list: D018684:Glycine Agents; D018009:Receptors, Glycine
keywords: GABA; action potential; excitability