Hypothalamic histaminergic and orexinergic modulation on the medial vestibular nucleus

【作者】 朱景宁； Jian-Jun Wang；

【Author】 Jing-Ning Zhu;Jian-Jun Wang;Department of Biological Science and Technology and State Key Laboratory of Pharmaceutical Biotechnology,School of Life Sciences,Nanjing University;

【机构】 南京大学； Department of Biological Science and Technology and State Key Laboratory of Pharmaceutical Biotechnology,School of Life Sciences,Nanjing University；

【摘要】 Central histaminergic system and central orexinergic system both restrictedly originate in the hypothalamus but innervate almost the whole brain,including various subcortical motor structures.In brainstem,the medial vestibular nucleus(MVN),a key motor center for stabilization,coordination and compensation of head and eye movements,receives direct hypothalamic histaminergic and orexinergic projections.Here,we report that both histamine and orexin postsynaptically excite type-A and type-Bneurons in the MVN in a concentration dependent manner.Na+-Ca2+exchangers(NCXs)coupled to histamine H1 receptors and hyperpolarization-activated cyclic nucleotide-gated(HCN)channels linked to histamine H2 receptors co-mediate the strong postsynaptic excitatory effect of histamine on the MVN neurons.On the other hand,orexin 1 receptors(OX1Rs)and orexin 2 receptors(OX2Rs),together with their downstream coupling NCXs and nonselective cation channels(NSCCs),underlie the excitation of orexin on the MVN neurons.Furthermore,orexin increased the sensitivity of MVN neurons to the rectangle and ramp current stimulations without altering neuronal dynamic properties.And orexin also caused a frequency-dependent gain enhancement and phase-lead shift of MVN neurons to sinusoid-like current stimulations.Interestingly,endogenous orexinergic modulation on MVN neurons was critical when animals traversing a rotating balance beam as opposed to a static one.All these results demonstrate that histamine and orexin modulates not only excitability but also sensitivity of the MVN neurons and suggest that hypothalamic histaminergic and orexinergic innervation on MVN may play a crucial role in somatic motor control.The findings also suggest novel potential targets for clinical treatment of vestibular disorders,such as vertigo,motion sickness,nausea and nystagmus.更多还原

【Abstract】 Central histaminergic system and central orexinergic system both restrictedly originate in the hypothalamus but innervate almost the whole brain,including various subcortical motor structures.In brainstem,the medial vestibular nucleus(MVN),a key motor center for stabilization,coordination and compensation of head and eye movements,receives direct hypothalamic histaminergic and orexinergic projections.Here,we report that both histamine and orexin postsynaptically excite type-A and type-Bneurons in the MVN in a concentration dependent manner.Na+-Ca2+ exchangers(NCXs) coupled to histamine H1 receptors and hyperpolarization-activated cyclic nucleotide-gated(HCN) channels linked to histamine H2 receptors co-mediate the strong postsynaptic excitatory effect of histamine on the MVN neurons.On the other hand,orexin 1 receptors(OX1Rs) and orexin 2 receptors(OX2Rs),together with their downstream coupling NCXs and nonselective cation channels(NSCCs),underlie the excitation of orexin on the MVN neurons.Furthermore,orexin increased the sensitivity of MVN neurons to the rectangle and ramp current stimulations without altering neuronal dynamic properties.And orexin also caused a frequency-dependent gain enhancement and phase-lead shift of MVN neurons to sinusoid-like current stimulations.Interestingly,endogenous orexinergic modulation on MVN neurons was critical when animals traversing a rotating balance beam as opposed to a static one.All these results demonstrate that histamine and orexin modulates not only excitability but also sensitivity of the MVN neurons and suggest that hypothalamic histaminergic and orexinergic innervation on MVN may play a crucial role in somatic motor control.The findings also suggest novel potential targets for clinical treatment of vestibular disorders,such as vertigo,motion sickness,nausea and nystagmus.更多还原