Accumulating evidence in vivo suggests that Shank proteins are required for proper synaptic function as well, but the findings are somewhat inconsistent. Extracellular recordings in the stratum radiatum of Shank1−/− mice revealed a significantly decreased excitatory synaptic strength, as assessed by the input-output relationship of field excitatory postsynaptic potentials, and recordings from CA1 hippocampal neurons in these mice revealed decreased mEPSC frequency (Hung et al, 2008). The two lines of Shank2 mutant mice have distinct electrophysiological phenotypes, despite the two mutations having presumably the same effect on Shank2 protein expression. Deletion of Shank2 exon 7 results in decreased excitatory synaptic strength, decreased mEPSC frequency, a decreased AMPA/NMDA current ratio, and increased LTP in the hippocampus (Schmeisser et al., 2012). However, deletion of Shank2 exons 6–7 results in no significant changes in excitatory synaptic transmission, an increase in the AMPA/NMDA current ratio, and impaired LTP and NMDA-dependent LTD (Won et al., 2012).
