Deletion of miR-150 Exacerbates Retinal Vascular Overgrowth in High-Fat-Diet Induced Diabetic Mice

Diabetic retinopathy (DR) is the leading cause of blindness among American adults above 40 years old. The vascular complication in DR is a major cause of visual impairment, making finding therapeutic targets to block pathological angiogenesis a primary goal for developing DR treatments. MicroRNAs (miRs) have been proposed as diagnostic biomarkers and potential therapeutic targets for various ocular diseases including DR. In diabetic animals, the expression levels of several miRs, including miR-150, are altered. The expression of miR-150 is significantly suppressed in pathological neovascularization in mice with hyperoxia-induced retinopathy. The purpose of this study was to investigate the functional role of miR-150 in the development of retinal microvasculature complications in high-fat-diet (HFD) induced type 2 diabetic mice. Wild type (WT) and miR-150 null mutant (miR-150-/-) male mice were given a HFD (59% fat calories) or normal chow diet. Chronic HFD caused a decrease of serum miR-150 in WT mice. Mice on HFD for 7 months (both WT and miR-150-/-) had significant decreases in retinal light responses measured by electroretinograms (ERGs). The retinal neovascularization in miR-150-/--HFD mice was significantly higher compared to their age matched WT-HFD mice, which indicates that miR-150 null mutation exacerbates chronic HFD-induced neovascularization in the retina. Overexpression of miR-150 in cultured endothelial cells caused a significant reduction of vascular endothelial growth factor receptor 2 (VEGFR2) protein levels. Hence, deletion of miR-150 significantly increased the retinal pathological angiogenesis in HFD induced type 2 diabetic mice, which was in part through VEGFR2

Systemic Effects of Selection History on Learned Ignoring

Despite our best intentions, physically salient but entirely task-irrelevant stimuli can sometimes capture our attention. With learning, it is possible to more efficiently ignore such stimuli, although specifically how the visual system accomplishes this remains to be clarified. Using a sample of young-adult participants, we examined the time course of eye movements to targets and distractors. We replicate a reduced frequency of eye movements to the distractor when appearing in a location at which distractors are frequently encountered. This reduction was observed even for the earliest saccades, when selection tends to be most stimulus-driven. When the distractor appeared at the high-probability location, saccadic reaction time was slowed specifically for distractor-going saccades, suggesting a slowing of priority accumulation at this location. In the event that the distractor was fixated, disengagement from the distractor was also faster when it appeared in the high-probability location. Both proactive and reactive mechanisms of distractor suppression work together to minimize attentional capture by frequently-encountered distractors

The effect of concurrent reward on aversive information processing in the brain

Neural networks for the processing of appetitive and aversive information, in isolation, have been well characterized. However, how the brain integrates competing signals associated with simultaneous appetitive and aversive information is less clear. In particular, it is unknown how the presence of concurrent reward modulates the processing of an aversive event throughout the brain. Here, we propose utilizing a four-armed bandit task in an fMRI study to measure the representation of an aversive electric shock with and without the simultaneous receipt of monetary reward. Using an ROI approach, we will first identify regions activated by the experience of aversive electric shock, and then measure how this shock-related activation is modulated by concurrent reward using independent data. Informed by prior literature and our own preliminary data, analyses will focus on the dorsolateral prefrontal cortex, anterior and posterior insula, anterior cingulate cortex, and the thalamus and somatosensory cortex. Of interest will be the extent to which responses to the aversive electric shock are attenuated due to the presence of concurrent reward, consistent with either the integration of valence signals or competition between punishment and reward

The effect of concurrent reward on aversive information processing in the brain

Stage 2 Registered Report Submission to NeuroImag

Reliably Measuring Learning-Dependent Distractor Suppression with Eye Tracking

In the field of psychological science, behavioral performance in computer-based cognitive tasks often exhibits poor reliability. The absence of reliable measures of cognitive processes contributes to non-reproducibility in the field and impedes investigation of individual differences. Specifically in visual search paradigms, response time-based measures have shown poor test-retest reliability and internal consistency across attention capture and distractor suppression, but one study has demonstrated the potential for oculomotor measures to exhibit superior reliability. Therefore, in this study, we investigated three datasets to compare the reliability of learning-dependent distractor suppression measured via distractor fixations (oculomotor capture) and latency to fixate the target (fixation times). Our findings reveal superior split-half reliability of oculomotor capture compared to that of fixation times regardless of the critical distractor comparison, with the reliability of oculomotor capture in most cases falling within the range that is acceptable for the investigation of individual differences. We additionally find that older adults have superior oculomotor reliability compared with young adults, potentially addressing a significant limitation in the aging literature of high variability in response time measures due to slower responses. Our findings highlight the utility of measuring eye movements in the pursuit of reliable indicators of distractor processing and the need to further test and develop additional measures in other sensory domains to maximize statistical power, reliability, and reproducibility

Neural Correlates of Value-Driven Spatial Orienting

Remainder of raw brain data accessible via this link: https://osf.io/t7dj5/?view_only=ca7cdbdcef6a491ebc7f57982ef9ca48 Paper accessible via this link: https://doi.org/10.1111/psyp.1432

Overexpression of miR-150 decreased VEGFR2 protein level in endothelial cells.

<p>The HUVE cells were transfected with miR-150 (has-miR-150) or a scramble microRNA (Scramble) and cultured for an additional 60 hr. The protein levels of c-Myb and VEGFR2 are significantly lower in HUVE cells with overexpression of miR-150 compared to the scramble (student’s <i>t</i>-test; *<i>p</i> < 0.05). n = 4 for each group. (B) The protein level of VEGFR2 is significantly lower in HRECs transfected with has-miR-150 compared to the ones transfected with scramble (student’s t-test; *p < 0.05). n = 4 for each group. (C) The retinas from WT and miR-150^-/- mice under normal chow diet (Normal) or HFD were isolated and processed for Western blotting. Some retinas were trypsin-digested to obtain the retinal vasculature followed by immunostaining with the VEGFR2 antibody conjugated with Alexa-488. The scale bar = 100 μm.</p