59 research outputs found

    A chronometric exploration of high-resolution ‘sensitive TMS masking’ effects on subjective and objective measures of vision

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    Transcranial magnetic stimulation (TMS) can induce masking by interfering with ongoing neural activity in early visual cortex. Previous work has explored the chronometry of occipital involvement in vision by using single pulses of TMS with high temporal resolution. However, conventionally TMS intensities have been high and the only measure used to evaluate masking was objective in nature. Recent studies have begun to incorporate subjective measures of vision, alongside objective ones. The current study goes beyond previous work in two regards. First, we explored both objective vision (an orientation discrimination task) and subjective vision (a stimulus visibility rating on a four-point scale), across a wide range of time windows with high temporal resolution. Second, we used a very sensitive TMS-masking paradigm: stimulation was at relatively low TMS intensities, with a figure-8 coil, and the small stimulus was difficult to discriminate already at baseline level. We hypothesized that this should increase the effective temporal resolution of our paradigm. Perhaps for this reason, we are able to report a rather interesting masking curve. Within the classical-masking time window, previously reported to encompass broad SOAs anywhere between 60 and 120 ms, we report not one, but at least two dips in objective performance, with no masking in-between. The subjective measure of vision did not mirror this pattern. These preliminary data from our exploratory design suggest that, with sensitive TMS masking, we might be able to reveal visual processes in early visual cortex previously unreported

    Tetraspanin 6: a pivotal protein of the multiple vesicular body determining exosome release and lysosomal degradation of amyloid precursor protein fragments

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    BACKGROUND: The mechanisms behind AÎČ-peptide accumulation in non-familial Alzheimer’s disease (AD) remain elusive. Proteins of the tetraspanin family modulate AÎČ production by interacting to Îł-secretase. METHODS: We searched for tetraspanins with altered expression in AD brains. The function of the selected tetraspanin was studied in vitro and the physiological relevance of our findings was confirmed in vivo. RESULTS: Tetraspanin-6 (TSPAN6) is increased in AD brains and overexpression in cells exerts paradoxical effects on Amyloid Precursor Protein (APP) metabolism, increasing APP-C-terminal fragments (APP-CTF) and AÎČ levels at the same time. TSPAN6 affects autophagosome-lysosomal fusion slowing down the degradation of APP-CTF. TSPAN6 recruits also the cytosolic, exosome-forming adaptor syntenin which increases secretion of exosomes that contain APP-CTF. CONCLUSIONS: TSPAN6 is a key player in the bifurcation between lysosomal-dependent degradation and exosome mediated secretion of APP-CTF. This corroborates the central role of the autophagosomal/lysosomal pathway in APP metabolism and shows that TSPAN6 is a crucial player in APP-CTF turnover

    Feedback Enhances Feedforward Figure-Ground Segmentation by Changing Firing Mode

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    In the visual cortex, feedback projections are conjectured to be crucial in figure-ground segregation. However, the precise function of feedback herein is unclear. Here we tested a hypothetical model of reentrant feedback. We used a previous developed 2-layered feedforwardspiking network that is able to segregate figure from ground and included feedback connections. Our computer model data show that without feedback, neurons respond with regular low-frequency (∌9 Hz) bursting to a figure-ground stimulus. After including feedback the firing pattern changed into a regular (tonic) spiking pattern. In this state, we found an extra enhancement of figure responses and a further suppression of background responses resulting in a stronger figure-ground signal. Such push-pull effect was confirmed by comparing the figure-ground responses withthe responses to a homogenous texture. We propose that feedback controlsfigure-ground segregation by influencing the neural firing patterns of feedforward projecting neurons
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