ThematurationoftheGABAergicsystemisacrucialdeterminantofcorticaldevelopmentduringearlypostnatallife,whensensorycircuitsundergoaprocessofactivity-dependentrefinement.Analteredexcitatory/inhibitorybalancehasbeenproposedasapossiblepathogenicmechanismofautismspectrumdisorders(ASD).Thehomeobox-containingtranscriptionfactorEngrailed-2(En2)hasbeenassociatedtoASD,andEn2knockout(En2-/-)miceshowASD-likefeaturesaccompaniedbyapartiallossofcorticalGABAergicinterneurons.HerewestudiedGABAergicmarkersandcorticalfunctioninEn2-/-mice,byexploitingthewell-knownanatomicalandfunctionalfeaturesofthemousevisualsystem.En2isexpressedinthevisualcortexatpostnatalday30andduringadulthood.Whencomparedtoage-matchedEn2+/+controls,En2-/-miceshowedanincreasednumberofparvalbumin(PV+),somatostatin(SOM+),andneuropeptideY(NPY+)positiveinterneuronsinthevisualcortexatP30,andadecreasednumberofSOM+andNPY+interneuronsintheadult.Atbothages,thedifferencesindistinctinterneuronpopulationsobservedbetweenEn2+/+andEn2-/-micewerelayer-specific.AdultEn2-/-micedisplayedanormaleye-specificsegregationintheretino-geniculatepathway,andinvivoelectrophysiologicalrecordingsshowedanormaldevelopmentofbasicfunctionalproperties(acuity,responselatency,receptivefieldsize)oftheEn2-/-primaryvisualcortex.However,asignificantincreaseofbinocularitywasfoundinP30andadultEn2-/-mice,ascomparedtoage-matchedcontrols.DifferentlyfromwhatobservedinEn2+/+mice,theEn2-/-primaryvisualcortexdidnotrespondtoabriefmonoculardeprivationperformedbetweenP26andP29,duringtheso-called"criticalperiod."ThesedatasuggestthatalteredGABAergiccircuitsimpactbaselinebinocularityandplasticityinEn2-/-mice,whileleavingothervisualfunctionalpropertiesunaffected.
AlteredGABAergicmarkers,increasedbinocularityandreducedplasticityinthevisualcortexofEngrailed-2knockoutmice
2014
Abstract
ThematurationoftheGABAergicsystemisacrucialdeterminantofcorticaldevelopmentduringearlypostnatallife,whensensorycircuitsundergoaprocessofactivity-dependentrefinement.Analteredexcitatory/inhibitorybalancehasbeenproposedasapossiblepathogenicmechanismofautismspectrumdisorders(ASD).Thehomeobox-containingtranscriptionfactorEngrailed-2(En2)hasbeenassociatedtoASD,andEn2knockout(En2-/-)miceshowASD-likefeaturesaccompaniedbyapartiallossofcorticalGABAergicinterneurons.HerewestudiedGABAergicmarkersandcorticalfunctioninEn2-/-mice,byexploitingthewell-knownanatomicalandfunctionalfeaturesofthemousevisualsystem.En2isexpressedinthevisualcortexatpostnatalday30andduringadulthood.Whencomparedtoage-matchedEn2+/+controls,En2-/-miceshowedanincreasednumberofparvalbumin(PV+),somatostatin(SOM+),andneuropeptideY(NPY+)positiveinterneuronsinthevisualcortexatP30,andadecreasednumberofSOM+andNPY+interneuronsintheadult.Atbothages,thedifferencesindistinctinterneuronpopulationsobservedbetweenEn2+/+andEn2-/-micewerelayer-specific.AdultEn2-/-micedisplayedanormaleye-specificsegregationintheretino-geniculatepathway,andinvivoelectrophysiologicalrecordingsshowedanormaldevelopmentofbasicfunctionalproperties(acuity,responselatency,receptivefieldsize)oftheEn2-/-primaryvisualcortex.However,asignificantincreaseofbinocularitywasfoundinP30andadultEn2-/-mice,ascomparedtoage-matchedcontrols.DifferentlyfromwhatobservedinEn2+/+mice,theEn2-/-primaryvisualcortexdidnotrespondtoabriefmonoculardeprivationperformedbetweenP26andP29,duringtheso-called"criticalperiod."ThesedatasuggestthatalteredGABAergiccircuitsimpactbaselinebinocularityandplasticityinEn2-/-mice,whileleavingothervisualfunctionalpropertiesunaffected.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
