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Immunohistochemical Visualization of Hippocampal Neuron Activity After Spatial Learning in a Mouse Model of Neurodevelopmental Disorders
Published on: May 12, 2015
MECP2 regulates cortical plasticity underlying a learned behaviour in adult female mice
Keerthi Krishnan1, Billy Y B Lau1, Gabrielle Ewall1
1Cold Spring Harbor Laboratory, 1 Bungtown Road, Cold Spring Harbor, New York 11724, USA.
Insights
Female Mecp2het mice, a model for Rett syndrome, show impaired pup gathering behavior due to disrupted auditory cortical plasticity. Restoring inhibitory network function rescued this social behavior.
Area of Science:
- Neuroscience
- Developmental Biology
- Genetics
Background:
- Neurodevelopmental disorders are characterized by abnormal synaptic connections early in life.
- The long-term impact of disrupted experience-dependent plasticity on adult cognitive and behavioral deficits remains poorly understood.
Purpose of the Study:
- To investigate the role of experience-dependent plasticity in adult cognitive and behavioral decline in a mouse model of Rett syndrome.
- To explore the mechanisms underlying impaired social behavior and auditory cortical plasticity in Mecp2het mice.
Main Methods:
- Utilized female Mecp2het mice as a model for Rett syndrome.
- Assessed pup gathering behavior and auditory cortical plasticity in response to learned maternal experience.
- Employed genetic and pharmacological manipulations targeting the GABAergic network.
Main Results:
- Mecp2het females exhibited impaired pup gathering behavior and altered auditory cortical plasticity.
- Learned maternal experience induced transient changes in cortical inhibitory networks in Mecp2het mice, indicative of limited plasticity.
- Restoration of GABAergic network function rescued the impaired gathering behavior.
Conclusions:
- Pup gathering learning normally triggers a transient period of inhibitory plasticity in the auditory cortex.
- This plasticity is dysregulated in Mecp2het mice, leading to suppressed adult plasticity independent of early developmental effects.
- Targeting the GABAergic network can restore social behavior in this model of Rett syndrome.
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 Mecp2het mice, a model of Rett syndrome. In response to learned maternal experience, Mecp2het females exhibited transient changes to cortical inhibitory networks typically associated with limited plasticity. Averting these changes in Mecp2het through 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.
