Restoring glutamate receptosome dynamics at synapses rescues autism-like deficits in Shank3-deficient mice.

Shank3 monogenic mutations lead to autism spectrum disorders (ASD). Shank3 is part of the glutamate receptosome that physically links ionotropic NMDA receptors to metabotropic mGlu5 receptors through interactions with scaffolding proteins PSD95-GKAP-Shank3-Homer. A main physiological function of the glutamate receptosome is to control NMDA synaptic function that is required for plasticity induction.

Another step toward understanding brain functional connectivity alterations in autism: An Editorial Highlight for "Neurobiological substrates underlying corpus callosum hypoconnectivity and brain metabolic patterns in the valproic acid rat model of autism spectrum disorder" on page 128.

Various neuroimaging approaches have reported alterations in brain connectivity in patients with autism spectrum disorder (ASD). Nevertheless, specific cellular and molecular mechanisms underlying these alterations remain to be elucidated. In the present Editorial, we highlight an article in the current issue of the Journal of Neurochemistry that provides first evidence for the structural and cellular basis of an atypical corpus callosum long-distance connectivity impairments observed in ASD patients.

N-methyl-d-aspartate receptor function in neuronal and synaptic development and signaling.

The N-methyl-d-aspartate (NMDA) receptor, among the ionotropic glutamate receptors, are fundamental to integrating and transducing complex signaling in neurons. Glutamate activation of these receptors mediates intracellular signals essential to neuronal and synaptic formation and synaptic plasticity and also contribute to excitotoxic processes in several neurological disorders. The NMDA receptor signaling is mediated by the permeability to Ca2+ and by the large network of signaling and scaffolding proteins associated mostly with the large C-terminal domain of GluN2 subunits.

Autism-associated SHANK3 mutations impair maturation of neuromuscular junctions and striated muscles.

Heterozygous mutations of the gene encoding the postsynaptic protein SHANK3 are associated with syndromic forms of autism spectrum disorders (ASDs). One of the earliest clinical symptoms in SHANK3-associated ASD is neonatal skeletal muscle hypotonia. This symptom can be critical for the early diagnosis of affected children; however, the mechanism mediating hypotonia in ASD is not completely understood.

High-Aspect-Ratio Semiconducting Polymer Pillars for 3D Cell Cultures.

Hybrid interfaces between living cells and nano/microstructured scaffolds have huge application potential in biotechnology, spanning from regenerative medicine and stem cell therapies to localized drug delivery and from biosensing and tissue engineering to neural computing. However, 3D architectures based on semiconducting polymers, endowed with responsivity to visible light, have never been considered. Here, we apply for the first time a push-coating technique to realize high aspect ratio polymeric pillars, based on polythiophene, showing optimal biocompatibility and allowing for the realization of soft, 3D cell cultures of both primary neurons and cell line models.