PT  - JOURNAL ARTICLE
AU  - Morello, Noemi
AU  - Schina, Riccardo
AU  - Pilotto, Federica
AU  - Phillips, Mary
AU  - Melani, Riccardo
AU  - Plicato, Ornella
AU  - Pizzorusso, Tommaso
AU  - Pozzo-Miller, Lucas
AU  - Giustetto, Maurizio
TI  - Loss of <em>Mecp2</em> Causes Atypical Synaptic and Molecular Plasticity of Parvalbumin-Expressing Interneurons Reflecting Rett Syndrome–Like Sensorimotor Defects
AID  - 10.1523/ENEURO.0086-18.2018
DP  - 2018 Sep 01
TA  - eneuro
PG  - ENEURO.0086-18.2018
VI  - 5
IP  - 5
4099  - http://www.eneuro.org/content/5/5/ENEURO.0086-18.2018.short
4100  - http://www.eneuro.org/content/5/5/ENEURO.0086-18.2018.full
SO  - eNeuro2018 Sep 01; 5
AB  - Rett syndrome (RTT) is caused in most cases by loss-of-function mutations in the X-linked gene encoding methyl CpG-binding protein 2 (MECP2). Understanding the pathological processes impacting sensory-motor control represents a major challenge for clinical management of individuals affected by RTT, but the underlying molecular and neuronal modifications remain unclear. We find that symptomatic male Mecp2 knockout (KO) mice show atypically elevated parvalbumin (PV) expression in both somatosensory (S1) and motor (M1) cortices together with excessive excitatory inputs converging onto PV-expressing interneurons (INs). In accordance, high-speed voltage-sensitive dye imaging shows reduced amplitude and spatial spread of synaptically induced neuronal depolarizations in S1 of Mecp2 KO mice. Moreover, motor learning-dependent changes of PV expression and structural synaptic plasticity typically occurring on PV+ INs in M1 are impaired in symptomatic Mecp2 KO mice. Finally, we find similar abnormalities of PV networks plasticity in symptomatic female Mecp2 heterozygous mice. These results indicate that in Mecp2 mutant mice the configuration of PV+ INs network is shifted toward an atypical plasticity state in relevant cortical areas compatible with the sensory-motor dysfunctions characteristics of RTT.