Effects of genetic deletion of the Kv4.2 voltage-gated potassium channel on murine anxiety-, fear- and stress-related behaviors.docVIP

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Effects of genetic deletion of the Kv4.2 voltage-gated potassium channel on murine anxiety-, fear- and stress-related behaviors.doc

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Effects of genetic deletion of the Kv4.2 voltage-gated potassium channel on murine anxiety-, fear- and stress-related behaviors

Kiselycznyketal.BiologyofMoodAnxietyDisorders2012,2:5 /content/2/1/5 Biology of Mood Anxiety Disorders RESEARCH OpenAccess EffectsofgeneticdeletionoftheKv4.2voltage- gatedpotassiumchannelonmurineanxiety-, fear-andstress-relatedbehaviors CarlyKiselycznyk1*,DaxAHoffman2andAndrewHolmes1 Abstract Background:Potassiumchannelshavebeenproposedtoplayaroleinmechanismsofneuralplasticity,andthe Kv4.2subunithasbeenimplicatedintheregulationofaction-potentialback-propagationtothedendrites. Alterationsinmechanismsofplasticityhavebeenfurtherproposedtounderlievariouspsychiatricdisorders,but theroleofKv4.2inanxietyordepressionisnotwellunderstood. Methods:Inthispaper,weanalyzedthephenotypeKv4.2knockoutmicebasedontheirneurologicalfunction,on abatteryofbehaviorsincludingthoserelatedtoanxietyanddepression,andonplasticity-relatedlearningtasks. Results:Wefoundanovelty-inducedhyperactivephenotypeinknockoutmice,andthesemicealsodisplayed increasedreactivitytonovelstimulussuchasanauditorytone.Noclearanxiety-ordepression-relatedphenotype wasobserved,noranyalterationsinlearning/plasticity-basedparadigms. Conclusions:WedidnotfindclearevidenceforaninvolvementofKv4.2inneuropsychiatricorplasticity-related phenotypes,buttherewassupportforaroleinKv4.2indampeningexcitatoryresponsestonovelstimuli. Background hippocampal neurons, Kv4.2 protein is primarily loca- Theexcitabilityandfunctionalplasticityofspecificbrain lized on dendrites [3] where they exert their strongest circuits in cortical, limbic, and midbrain regions is functionaleffects[4].GenedeletionofKv4.2(Kcnd2 )in thoughttomediatebehavioralresponsestoenvironmen- mice eliminates most of the A-type K+ current in hip- talthreats,andtoenableadaptationtostressors.Atthe pocampal and cortical neurons [5-7], and increases cellular level, voltage- andcalcium-activated potassium back-propagation oftheactionpotential fromtheaxon (K+)channelsprovideanimportantmeansofmodulat- to the somatodendritic region [6]. These and other in