Defective Synapse Maturation and Enhanced Synaptic Plasticity in Shank2 Δex7-/- Mice

ENeuro
Stephanie WegenerDietmar Schmitz

Abstract

Autism spectrum disorders (ASDs) are neurodevelopmental disorders with a strong genetic etiology. Since mutations in human SHANK genes have been found in patients with autism, genetic mouse models are used for a mechanistic understanding of ASDs and the development of therapeutic strategies. SHANKs are scaffold proteins in the postsynaptic density of mammalian excitatory synapses with proposed functions in synaptogenesis, regulation of dendritic spine morphology, and instruction of structural synaptic plasticity. In contrast to all studies so far on the function of SHANK proteins, we have previously observed enhanced synaptic plasticity in Shank2 Δex7-/- mice. In a series of experiments, we now reproduce these results, further explore the synaptic phenotype, and directly compare our model to the independently generated Shank2 Δex6-7-/- mice. Minimal stimulation experiments reveal that Shank2 Δex7-/- mice possess an excessive fraction of silent (i.e., α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid, short, AMPA receptor lacking) synapses. The synaptic maturation deficit emerges during the third postnatal week and constitutes a plausible mechanistic explanation for the mutants' increased capacity for long-term potentiation, ...Continue Reading

Citations

Dec 27, 2018·PLoS Biology·Plinio D FavaroOliver M Schlüter
Apr 23, 2020·American Journal of Physiology. Cell Physiology·Juliette E Cheyne, Johanna M Montgomery
Jan 11, 2019·Frontiers in Cellular Neuroscience·Shiqi GuangJing Peng

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