title: Pre- and postsynaptic modulations of hypoglossal motoneurons by α-adrenoceptor activation in wild-type and Mecp2(-/Y) mice.
abstract: Hypoglossal motoneurons (HNs) control tongue movement and play a role in maintenance of upper airway patency. Defects in these neurons may contribute to the development of sleep apnea and other cranial motor disorders including Rett syndrome (RTT). HNs are modulated by norepinephrine (NE) through α-adrenoceptors. Although postsynaptic mechanisms are known to play a role in this effect, how NE modulates the synaptic transmissions of HNs remains poorly understood. More importantly, the NE system is defective in RTT, while how the defect affects HNs is unknown. Believing that information of NE modulation of HNs may help the understanding of RTT and the design of new therapeutical interventions to motor defects in the disease, we performed these studies in which glycinergic inhibitory postsynaptic currents and intrinsic membrane properties were examined in wild-type and Mecp2(-/Y) mice, a mouse of model of RTT. We found that activation of α1-adrenoceptor facilitated glycinergic synaptic transmission and excited HNs. These effects were mediated by both pre- and postsynaptic mechanisms. The latter effect involved an inhibition of barium-sensitive G protein-dependent K(+) currents. The pre- and postsynaptic modulations of the HNs by α1-adrenoceptors were not only retained in Mecp2-null mice but also markedly enhanced, which appears to be a compensatory mechanism for the deficiencies in NE and GABAergic synaptic transmission. The existence of the endogenous compensatory mechanism is an encouraging finding, as it may allow therapeutical modalities to alleviate motoneuronal defects in RTT.
authors.affiliation: Department of Biology, Georgia State University, Atlanta, Georgia.
authors.forename: Xiao-Tao
authors.initials: XT
authors.lastname: Jin
authors.forename: Ningren
authors.initials: N
authors.lastname: Cui
authors.forename: Weiwei
authors.initials: W
authors.lastname: Zhong
authors.forename: Xin
authors.initials: X
authors.lastname: Jin
authors.forename: Zhongying
authors.initials: Z
authors.lastname: Wu
authors.forename: Chun
authors.initials: C
authors.lastname: Jiang
mesh_terms: D000818:Animals; D002462:Cell Membrane / Q000502:physiology; D055724:Electrophysiological Phenomena; D005786:Gene Expression Regulation / Q000502:physiology; D007002:Hypoglossal Nerve / Q000166:cytology*; D008297:Male; D051783:Methyl-CpG-Binding Protein 2 / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D009046:Motor Neurons / Q000502:physiology*; D009154:Mutation; D018408:Patch-Clamp Techniques; D011942:Receptors, Adrenergic, alpha / Q000235:genetics / Q000378:metabolism*; D013569:Synapses
chemical_list: C497393:Mecp2 protein, mouse; D051783:Methyl-CpG-Binding Protein 2; D011942:Receptors, Adrenergic, alpha
keywords: IPSCs; Rett syndrome; hypoglossal motorneurons; norepinephrine; α1-adrenoceptor