title: MECP2 regulates cortical plasticity underlying a learned behaviour in adult female mice.
abstract: Neurodevelopmental disorders are marked by inappropriate synaptic connectivity early in life, but how disruption of experience-dependent plasticity contributes to cognitive and behavioural decline in adulthood is unclear. Here we show that pup gathering behaviour and associated auditory cortical plasticity are impaired in female Mecp2hetmice, a model of Rett syndrome. In response to learned maternal experience, Mecp2hetfemales exhibited transient changes to cortical inhibitory networks typically associated with limited plasticity. Averting these changes in Mecp2hetthrough genetic or pharmacological manipulations targeting the GABAergic network restored gathering behaviour. We propose that pup gathering learning triggers a transient epoch of inhibitory plasticity in auditory cortex that is dysregulated in Mecp2het. In this window of heightened sensitivity to sensory and social cues, Mecp2 mutations suppress adult plasticity independently from their effects on early development.
authors.affiliation: Cold Spring Harbor Laboratory, 1 Bungtown Road, Cold Spring Harbor, New York 11724, USA.
authors.forename: Keerthi
authors.identifier: 0000-0002-0858-4624
authors.initials: K
authors.lastname: Krishnan
authors.affiliation: Cold Spring Harbor Laboratory, 1 Bungtown Road, Cold Spring Harbor, New York 11724, USA.
authors.forename: Billy Y B
authors.initials: BY
authors.lastname: Lau
authors.affiliation: Cold Spring Harbor Laboratory, 1 Bungtown Road, Cold Spring Harbor, New York 11724, USA.
authors.forename: Gabrielle
authors.initials: G
authors.lastname: Ewall
authors.affiliation: Cold Spring Harbor Laboratory, 1 Bungtown Road, Cold Spring Harbor, New York 11724, USA.
authors.forename: Z Josh
authors.initials: ZJ
authors.lastname: Huang
authors.affiliation: Cold Spring Harbor Laboratory, 1 Bungtown Road, Cold Spring Harbor, New York 11724, USA.
authors.forename: Stephen D
authors.initials: SD
authors.lastname: Shea
mesh_terms: D000818:Animals; D002540:Cerebral Cortex / Q000378:metabolism / Q000503:physiopathology*; D005260:Female; D006801:Humans; D007858:Learning; D008297:Male; D008425:Maternal Behavior; D051783:Methyl-CpG-Binding Protein 2 / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009473:Neuronal Plasticity; D015518:Rett Syndrome / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology / Q000523:psychology*; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
chemical_list: D051783:Methyl-CpG-Binding Protein 2; D005680:gamma-Aminobutyric Acid