ABSTRACT
The neurodevelopmental disorder Rett syndrome is caused by mutations in the gene Mecp2. Misexpression of the protein MECP2 is thought to contribute to neuropathology by causing dysregulation of plasticity. Female heterozygous Mecp2 mutants (Mecp2het) failed to acquire a learned maternal retrieval behavior when exposed to pups, an effect linked to disruption of parvalbumin-expressing inhibitory interneurons (PV+) in the auditory cortex. However, the consequences of dysregulated PV+ networks during early maternal experience for auditory cortical sensory activity are unknown. Here we show that maternal experience in wild-type adult female mice (Mecp2wt) triggers suppression of PV+ auditory responses. We also observe concomitant disinhibition of auditory responses in deep-layer pyramidal neurons that is selective for behaviorally-relevant pup vocalizations. These neurons also exhibit sharpened tuning for pup vocalizations following maternal experience. All of these neuronal changes are abolished in Mecp2het, yet a genetic manipulation of GABAergic networks that restores accurate retrieval behavior in Mecp2het also restores maternal experience-dependent plasticity of PV+. Our data are consistent with a growing body of evidence that cortical networks are particularly vulnerable to mutations of Mecp2 in PV+ neurons.
Footnotes
Author Contributions: SDS and ZJH supervised the project. BYBL, KK, and SDS designed the experiments and developed the methods. BYBL and SDS collected and analyzed the data. BYBL, KK, ZJH and SDS wrote and edited the paper.
Added new data showing that a genetic manipulation that restores behavior also partially restores PV neuron plasticity (Figure 9)