Anesthetics Rapidly Promote Synaptogenesis during a Critical Period of Brain Development 英文参考文献.docVIP

AnestheticsRapidlyPromoteSynaptogenesisduringa CriticalPeriodofBrainDevelopment MathiasDeRoo1.,PaulKlauser1.,AdrianBriner1,2,IrinaNikonenko1,PabloMendez1 ,Alexandre Dayer1,3,JozsefZ.Kiss1,DominiqueMuller1,LaszloVutskits1,2* 1Department of Neuroscience, Faculty of Medicine, University of Geneva, Geneva, Switzerland, 2Department of Anesthesiology, Pharmacology and Intensive Care, UniversityHospitalofGeneva,Geneva,Switzerland,3DepartmentofAdultPsychiatry,UniversityHospitalofGeneva,Geneva,Switzerland Abstract Experience-driven activity plays an essential role in the development of brain circuitry during critical periods of early postnatal life, a process that depends upon a dynamic balance between excitatory and inhibitory signals. Since general anestheticsarepowerfulpharmacologicalmodulatorsofneuronalactivity,animportantquestioniswhetherandhowthese drugscanaffectthedevelopmentofsynapticnetworks.Toaddressthisissue,weexaminedheretheimpactofanesthetics onsynapsegrowthanddynamics.WeshowthatexposureofyoungrodentstoanestheticsthateitherenhanceGABAergic inhibitionorblock NMDAreceptors rapidly induceasignificantincrease indendriticspine densityin thesomatosensory cortex and hippocampus. This effect is developmentally regulated; it is transient but lasts for several days and is also reproduced by selective antagonists of excitatory receptors. Analyses of spine dynamics in hippocampal slice cultures reveals that this effect is mediated through an increased rate of protrusions formation, a better stabilization of newly formed spines, and leads to the formation of functional synapses. Altogether, these findings point to anesthesia as an important modulator of spine dynamics in the developing brain and suggest the existence of a homeostatic process regulatingspineformationasafunctionofneuralactivity.Importantly,theyalsoraiseconcernaboutthepotentialimpactof thesedrugsonhumanpractice,whenappliedduringcriticalperiodsofdevelopmentininfants. Citation: De Roo M, Klauser P, Briner A,