1. Gevarter C, O’Reilly MF, Kuhn M, Mills K, Ferguson R, Watkins L, Sigafoos J, Lang R, Rojeski L, Lancioni GE. {{Increasing the vocalizations of individuals with autism during intervention with a speech-generating device}}. {J Appl Behav Anal};2015 (Dec 6)
This study aimed to teach individuals with autism spectrum disorder (ASD) and limited vocal speech to emit target vocalizations while using a speech-generating device (SGD). Of the 4 participants, 3 began emitting vocal word approximations with SGD responses after vocal instructional methods (delays, differential reinforcement, prompting) were introduced. Two participants met mastery criterion with a reinforcer delay and differential reinforcement, and 1 met criterion after fading an echoic model and prompt delay. For these participants, vocalizations initiated before speech outputs were shown to increase, and vocalizations generalized to a context in which the SGD was absent. The 4th participant showed high vocalization rates only when prompted. The results suggest that adding vocal instruction to an SGD-based intervention can increase vocalizations emitted along with SGD responses for some individuals with ASD.
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2. Guo W, Ceolin L, Collins KA, Perroy J, Huber KM. {{Elevated CaMKIIalpha and Hyperphosphorylation of Homer Mediate Circuit Dysfunction in a Fragile X Syndrome Mouse Model}}. {Cell Rep};2015 (Dec 6)
Abnormal metabotropic glutamate receptor 5 (mGluR5) function, as a result of disrupted scaffolding with its binding partner Homer, contributes to the pathophysiology of fragile X syndrome, a common inherited form of intellectual disability and autism caused by mutations in Fmr1. How loss of Fmr1 disrupts mGluR5-Homer scaffolds is unknown, and little is known about the dynamic regulation of mGluR5-Homer scaffolds in wild-type neurons. Here, we demonstrate that brief (minutes-long) elevations in neural activity cause CaMKIIalpha-mediated phosphorylation of long Homer proteins and dissociation from mGluR5 at synapses. In Fmr1 knockout (KO) cortex, Homers are hyperphosphorylated as a result of elevated CaMKIIalpha protein. Genetic or pharmacological inhibition of CaMKIIalpha or replacement of Homers with dephosphomimetics restores mGluR5-Homer scaffolds and multiple Fmr1 KO phenotypes, including circuit hyperexcitability and/or seizures. This work links translational control of an FMRP target mRNA, CaMKIIalpha, to the molecular-, cellular-, and circuit-level brain dysfunction in a complex neurodevelopmental disorder.
