Defective synapse maturation and enhanced synaptic plasticity in Shank2-/- mice

Autism spectrum disorders (ASDs) are neurodevelopmental disorders with a strong genetic aetiology. Since mutations in human SHANK genes have been found in patients with autism, genetic mouse models are employed for a mechanistic understanding of ASDs and the development of therapeutic strategies. In sharp contrast to all studies so far on the function of SHANK proteins, we observe enhanced synaptic plasticity in Shank2-/- mice, under various conditions in vitro and in vivo. Reproducing and extending previous results, we here present a plausible mechanistic explanation for the mutants' increased capacity for long-term potentiation (LTP) by describing a synaptic maturation deficit in Shank2-/- mice.