Emerging issues and current trends in assistive technology use 2007-1010: practising, assisting and enabling learning for all

Following an earlier review in 2007, a further review of the academic literature relating to the uses of assistive technology (AT) by children and young people was completed, covering the period 2007-2011. As in the earlier review, a tripartite taxonomy: technology uses to train or practise, technology uses to assist learning and technology uses to enable learning, was used in order to structure the findings. The key markers for research in this field and during these three years were user involvement, AT on mobile mainstream devices, the visibility of AT, technology for interaction and collaboration, new and developing interfaces and inclusive design principles. The paper concludes by locating these developments within the broader framework of the Digital Divide

Active zone proteins are dynamically associated with synaptic ribbons in rat pinealocytes

Synaptic ribbons (SRs) are prominent organelles that are abundant in the ribbon synapses of sensory neurons where they represent a specialization of the cytomatrix at the active zone (CAZ). SRs occur not only in neurons, but also in neuroendocrine pinealocytes where their function is still obscure. In this study, we report that pinealocyte SRs are associated with CAZ proteins such as Bassoon, Piccolo, CtBP1, Munc13–1, and the motorprotein KIF3A and, therefore, consist of a protein complex that resembles the ribbon complex of retinal and other sensory ribbon synapses. The pinealocyte ribbon complex is biochemically dynamic. Its protein composition changes in favor of Bassoon, Piccolo, and Munc13–1 at night and in favor of KIF3A during the day, whereas CtBP1 is equally present during the night and day. The diurnal dynamics of the ribbon complex persist under constant darkness and decrease after stimulus deprivation of the pineal gland by constant light. Our findings indicate that neuroendocrine pinealocytes possess a protein complex that resembles the CAZ of ribbon synapses in sensory organs and whose dynamics are under circadian regulation

Antidepressant ketamine and its metabolite hydroxynorketamine converge on the regulation of neurotransmitter release

Major depressive disorder (MDD) is a devitalizing psychiatric condition with a lifetime prevalence of 17%. Alterations in glutamatergic transmission and plasticity have been closely associated with MDD. Ketamine is an activity-dependent blocker of NMDA receptors (NMDAR) which, at low subanesthetic doses show rapid and sustained antidepressant effect in treatment resistant patients. Changes in neuronal plasticity and synaptic transmission have been associated with antidepressant effects of ketamine. However, psychotomimetic effects and abuse potential of ketamine cannot be ignored and thus, its off-label use remains limited. A fairly recent study suggested that not ketamine but its metabolite hydroxynorketamine (HNK), which does not act via NMDAR, mediates the rapid antidepressant action. The molecular mechanisms of ketamine and HNK induced antidepressant effect remain enigmatic. In this study, we set up to monitor the effects of ketamine and HNK in cultured cortical neurons using live-cell imaging and electrophysiology, to investigate the convergent and divergent effects of these drugs on neurotransmission, signaling and gene expression, at the level of individual cells and synapses. Our results indicate that low doses of ketamine and HNK show convergent effect on neurotransmitter release and thus modulate neurotransmission rapidly and persistently. Hereon, we provide a mechanistic understanding of cellular signaling mediating the antidepressant effect of ketamine and its metabolite HNK

A multiple Piccolino-RIBEYE interaction supports plate-shaped synaptic ribbons in retinal neurons

Active zones at chemical synapses are highly specialized sites for the regulated release of neurotransmitters. Despite a high degree of active zone protein conservation in vertebrates, every type of chemical synapse expresses a given set of protein isoforms and splice variants adapted to the demands on neurotransmitter release. So far, we know little about how specific active zone proteins contribute to the structural and functional diversity of active zones. In this study, we explored the nano-domain organization of ribbon-type active zones by addressing the significance of Piccolino, the ribbon synapse specific splice variant of Piccolo, for shaping the ribbon structure. We followed up on previous results, which indicated that rod photoreceptor synaptic ribbons lose their structural integrity in a knockdown of Piccolino. Here, we demonstrate an interaction between Piccolino and the major ribbon component RIBEYE that supports plate-shaped synaptic ribbons in retinal neurons. In a detailed ultrastructural analysis of three different types of retinal ribbon synapses in Piccolo/Piccolino deficient male and female rats, we show that the absence of Piccolino destabilizes the superstructure of plate-shaped synaptic ribbons, although with variable manifestation in the cell types examined. Our analysis illustrates how the expression of a specific active zone protein splice variant, like Piccolino, contributes to structural diversity of vertebrate active zones. SIGNIFICANCE STATEMENT: Retinal ribbon synapses are a specialized type of chemical synapse adapted for the regulated fast and tonic release of neurotransmitter. The hallmark of retinal ribbon synapses is the plate-shaped synaptic ribbon, which extends from the release site into the terminals' cytoplasm and tethers hundreds of synaptic vesicles. Here, we show that Piccolino, the synaptic ribbon specific splice variant of Piccolo, interacts with RIBEYE, the main component of synaptic ribbons. This interaction occurs via several PxDLS-like motifs located at the C-terminus of Piccolino, which can connect multiple RIBEYE molecules. Loss of Piccolino disrupts the characteristic plate-shaped structure of synaptic ribbons indicating a role of Piccolino in synaptic ribbon assembly