Altered mGluR5-Homer scaffolds and corticostriatal connectivity in a Shank3 complete knockout model of autism

Human neuroimaging studies suggest that aberrant neural connectivity underlies behavioural deficits in autism spectrum disorders (ASDs), but the molecular and neural circuit mechanisms underlying ASDs remain elusive. Here, we describe a complete knockout mouse model of the autism-associated Shank3 gene, with a deletion of exons 4–22 (Δe4–22). Both mGluR5-Homer scaffolds and mGluR5-mediated signalling are selectively altered in striatal neurons. These changes are associated with perturbed function at striatal synapses, abnormal brain morphology, aberrant structural connectivity and ASD-like behaviour. In vivo recording reveals that the cortico-striatal-thalamic circuit is tonically hyperactive in mutants, but becomes hypoactive during social behaviour. Manipulation of mGluR5 activity attenuates excessive grooming and instrumental learning differentially, and rescues impaired striatal synaptic plasticity in Δe4–22−/− mice. These findings show that deficiency of Shank3 can impair mGluR5-Homer scaffolding, resulting in cortico-striatal circuit abnormalities that underlie deficits in learning and ASD-like behaviours. These data suggest causal links between genetic, molecular, and circuit mechanisms underlying the pathophysiology of ASDs

Nursing Student and Clinical Faculty Perceptions of the Three Safety Checks When Used with Medication Administration Technology

For patient safety, it is important that medication administration safety checks and procedures learned in school translate into use in professional practice. As more technology is being used in healthcare, educational programs are challenged to keep pace with the most current clinical technologies. By gaining insight into medication administration difficulties faced by students transitioning into clinical and perspectives of their clinical instructors, this quality improvement project aimed to identify areas of medication safety with the most discrepancy between education and practice to develop strategies to enhance medication administration education. At the University of North Carolina at Chapel Hill School of Nursing, eight clinical faculty were interviewed regarding their students’ experiences administering medications. Four nursing students participated in two focus groups where they were asked about their medication administration experiences in lab and translation of that content into clinical practice, with a focus on the three medication safety checks. While unable to complete checks as taught in lab, students and faculty adapted their practice to perform checks that worked with technology being used. One of the major points of feedback from students was the desire to learn in lab how the pattern of medication administration aligned with technologies used. All clinical faculty agreed that a more realistic lab environment, including medication administration technology, would be helpful as students learn medication administration. Moving forward, priorities should include alterations to the lab curriculum to teach a system of three safety checks that can be used without change with current medication administration technology.Bachelor of Scienc