title: Temporal change in NMDA receptor signaling and GABAA receptor expression in rat caudal vestibular nucleus during motion sickness habituation.
abstract: Repeated exposure to a provocative motion stimulus leads to motion sickness habituation indicative of the existence of central processes to counteract the disturbing properties of the imposed motion. In the present study, we attempt to investigate whether NMDA and GABA(A) receptors in rat caudal vestibular nucleus neurons are involved in motion sickness habituation induced by repeated Ferris-wheel like rotation in daily session (2h/d). We showed that defecation response increased and spontaneous locomotion decreased within 4 sessions (sickness phase). They recovered back to the control level after 7 sessions (habituation phase). Western blot analysis found that NMDA receptor signal molecules: calmodulin protein kinase II and cAMP response element-binding protein (CREB) were both activated during sickness phase, while a prolonged CREB activation was also observed during habituation phase. Real-time quantitative PCR revealed an increase in c-fos and a decrease in Arc mRNA level during sickness phase. We also found an increase in GABA(A) receptor α1 subunit (GABA(A) α1) protein level in this stage. These results suggested that altered NMDA receptor signaling and GABA(A) receptor expression level in caudal vestibular nucleus were associated with motion sickness habituation. Furthermore, immunofluorescence and confocal laser scanning microscopy showed that the number of GABA(A) α1 immunolabeled neurons in caudal vestibular nucleus increased while the number of GABA(A) α1/Arc double labeled neurons and the average amount of Arc particle in soma of these neurons decreased during sickness phase. It suggested that GABA(A) receptor level might be negatively regulated by Arc protein in caudal vestibular nucleus neurons.
authors.affiliation: Department of Military Hygiene, Faculty of Naval Medicine, Second Military Medical University, 800 Xiang Yin Road, Shanghai, China.
authors.forename: Jun-Qin
authors.initials: JQ
authors.lastname: Wang
authors.forename: Hong-Xia
authors.initials: HX
authors.lastname: Li
authors.forename: Xin-Min
authors.initials: XM
authors.lastname: Chen
authors.forename: Feng-Feng
authors.initials: FF
authors.lastname: Mo
authors.forename: Rui-Rui
authors.initials: RR
authors.lastname: Qi
authors.forename: Jun-Sheng
authors.initials: JS
authors.lastname: Guo
authors.forename: Yi-Ling
authors.initials: YL
authors.lastname: Cai
mesh_terms: D000818:Animals; D017362:Cyclic AMP Response Element-Binding Protein / Q000096:biosynthesis; D003598:Cytoskeletal Proteins / Q000096:biosynthesis; D006185:Habituation, Psychophysiologic / Q000502:physiology*; D008297:Male; D009041:Motion Sickness / Q000378:metabolism*; D009043:Motor Activity / Q000502:physiology; D009419:Nerve Tissue Proteins / Q000096:biosynthesis; D051381:Rats; D017207:Rats, Sprague-Dawley; D011963:Receptors, GABA-A / Q000096:biosynthesis*; D016194:Receptors, N-Methyl-D-Aspartate / Q000096:biosynthesis* / Q000235:genetics; D012399:Rotation / Q000009:adverse effects; D015398:Signal Transduction / Q000502:physiology*; D013997:Time Factors; D014726:Vestibular Nuclei / Q000378:metabolism*
chemical_list: D017362:Cyclic AMP Response Element-Binding Protein; D003598:Cytoskeletal Proteins; D009419:Nerve Tissue Proteins; D011963:Receptors, GABA-A; D016194:Receptors, N-Methyl-D-Aspartate; C092069:activity regulated cytoskeletal-associated protein