Shanks (also known as ProSAPs/Shanks) are large multidomain proteins that localize to excitatory synapses in the mammalian brain, where they are believed to organize the protein scaffold of the postsynaptic density (PSD). Structurally, Shanks are coupling glutamate receptor scaffolds to the actin cytoskeleton and intracellular signalling pathways by means of their protein- protein interaction domains. Functional studies suggest that Shanks may be important scaffold molecules with a crucial role

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... in the assembly of the PSD during synaptogenesis, in the structural instruction of synaptic plasticity, and in the regulation of dendritic spine morphology. Mutations in all three human SHANK genes have been directly linked to patients diagnosed with autism and/or cognitive disability. Shank2 deficient mice have recently been generated by the laboratory of Prof. Dr. Tobias Böckers (Ulm University, Germany) and we electrophysiologically characterized neuronal transmission of these mice in the CA1 region of the hippocampus. Performing extracellular recordings of evoked field potentials and intracellular whole-cell patchclamp recordings of spontaneous synaptic transmission, we found that Shank2-/- mice suffer from a selective decrease of excitatory synaptic transmission in hippocampal CA1. Recordings of AMPA/NMDA receptor ratios and minimal stimulation experiments revealed that Shank2‑/- mice suffer from attenuated synaptic maturation, a phenotype that becomes manifest over the course of the fourth postnatal week. Specifically, we found that CA1 pyramidal cells in adolescent (P21-P28), but not juvenile (P13-P14) Shank2‑/- mice harbour an unusually high fraction of silent synapses. Those synapses that contain AMPA receptors, have a reduced potency. Knockout mice are, however, capable of long-term plasticity as they showed normal long-term depression and increased long-term potentiation. These results confirm a role for Shank2 in the development of excitatory synapses. The late onset of the phenotype in Shank2‑/- mice, however, [...]