42,350 research outputs found

    Unraveling the role of active dendrites of Dentate Gyrus Granule cells using a biologically relevant computational model

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    Hippocampus is known to be involved in numerous memory processes, including episodic and spatial memory. The hippocampal Dentate Gyrus (DG) is believed to be responsible for distinguishing between similar mnemonic events, a computation known as pattern separation. Granule cells, the principal neurons of the DG, are thought to perform pattern separation by minimizing the overlap between similar patterns. Granule cells are sparsely connected, fire scarcely due to strong attenuation of propagating synaptic currents, and integrate strong inhibitory signals, generating a "winner-takes-all" mechanism. Moreover, recent findings suggest that the dendrites of GCs are able to support local regenerative events, the so-called dendritic spikes, whose potential functional role remains unclear. In this thesis, we create a biologically constrained, computational model of the Dentate Gyrus network that consists of GCs and various interneurons (Basket cells, HIPP cells, CCK cells) simulated as integrate-and-fire models. We used the model to assess the relative importance of the various characteristics of GC, focusing primarily on how active dendrites may influence pattern separation. Preliminary results predict that active dendrites facilitate pattern separation via decreasing the activity of Granule cells and thus increasing network sparsity. Further investigation is necessary to explain this unexpected finding, via a detailed biophysical model and/or in vitro dendro-somatic recordings

    FMRP and MOV10 regulate local DICER1 expression and dendrite development

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    RNA binding proteins (RBPs) are involved in all aspects of the RNA life cycle and constitute a critical component of maintaining proper transcription and translation. RBPs act as mediators of the critical intermediate between DNA and proteins, messenger RNA (mRNA), which is required for cell survival and growth. RBPs form ribonucleoprotein (RNP) complexes with their target mRNAs. Over 500 genes encode RBPs in human DNA, and although RBPs have a crucial role in post-translational regulation of gene expression, few have been studied systematically. In the nervous system, RBPs and their associated mRNAs, play a key role in normal neuronal development and function and in neurological disease. Fragile X syndrome, a cognitive impairment disorder, results from the loss of expression of the Fragile X Mental Retardation Protein (FMRP). FMRP associates with the RNA helicase Moloney Leukemia Virus 10 (Mov10) in brain and modulates its translational activity through the microRNA (miRNA) pathway. We previously showed that MOV10 is important in developing and maintaining normal brain activity using both murine and Xenopus models. The deletion of Mov10 in Neuro2a cells caused abnormally decreased neurite outgrowth on differentiation which was restored upon exogenous expression of MOV10. Furthermore, culturing and staining of hippocampal neurons from MOV10 Heterozygotes (Het) confirmed these results showing markedly short dendrites as seen in the Mov10 knockout Neuro2a cells suggesting impaired neuronal function (Skariah et al., 2017). We were thus interested in investigating the consequences of Mov10 and Fmr1 reduction on dendritic development. Mov10 Het and Fmr1 KO neurons possess an abnormal morphology compared to WT neurons at day in vitro 14 (DIV14). Additionally, Mov10 Het mice have reduced density of immature dendritic spines compared to WT and a smaller soma. The impaired neurite phenotype, spine maturation and reduced soma size have previously all been found to be associated with impaired miRNA biogenesis, and since MOV10 and FMRP are involved in regulation of the miRNA pathway, we sought to determine whether misregulation of the pathway was contributing to the abnormal neuronal phenotypes we observed in culture. We found a global reduction of Argonaute-2 (AGO2) – associated miRNAs in the absence of FMRP. This is important because AGO2 is the main effector of miRNA- mediated regulation. Furthermore, another component of the miRNA pathway, DICER, a ribonuclease which regulates biogenesis of miRNA and small interfering RNA (siRNA), was significantly decreased in the absence of MOV10 and FMRP. Through a series of knockdown and luciferase reporter experiments, we determined that MOV10 and FMRP modulate expression of the Dicer1 mRNA via the 3’ untranslated region (UTR). Overexpression (OE) of MYC-Dicer1 rescues the impaired neuronal phenotype in Mov10 Het neurons suggesting a mechanism for regulating local DICER expression when MOV10 and FMRP are present. Our work represents a new understanding of how FMRP and MOV10 regulate cobound mRNAs and neuronal development.LimitedAuthor requested closed access (OA after 2yrs) in Vireo ETD syste

    Open-cell Metallic Foams for the Electrochemical Conversion of Biomass-derived Compounds

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    The electrochemical conversion is a sustainable way for the production of added-value products, operating in mild conditions, using in-situ generated hydrogen/oxygen by water and avoiding the use of high H2/O2 pressures. The aim of this work is to investigate the electrocatalytic conversion of 5-hydroxymetilfurfural (HMF) and D-glucose, in alkaline media, using metallic open-cell foams based-catalysts. The electrochemical hydrogenation of HMF to 2,5-bis(hydroxymethyl)furan (BHMF) was performed using nanostructured Ag, deposited by galvanic displacement (GD) or electrodeposition (ED), on Cu foam, obtaining AgCu bimetallic nanoparticles (ED) or dendrites (GD) which enhanced electroactive surface area, charge and mass transfer, than bare foams. In diluted 0.02M HMF solutions, Ag/Cu samples selectively produce BHMF; the large surface area enhanced the productivity, compared to their 2D counterparts. Furthermore, at more concentrated solutions (0.05 – 0.10M) a gradually decrease of selectivity is observed. The performances of the electrodes is stable during the catalytic tests but a Cu-enrichment of particles occurred. The performances of Ni foam-based catalysts, obtained by calcination of Ni foam or by electrodeposition of Ni-hydroxide/Ni and Ni particle/Ni, were firstly investigated for the selective electrochemical oxidation of D-glucose toward gluconic acid (GO) and glucaric acid (GA). Then, the calcined catalyst was chosen to study the influence of the reaction conditions on the reaction mechanism. The GO and GA selectivities increase with the charge passed, while the formation of by-products from C-C cleavage/retro-aldol process is maximum at low charge. The fructose obtained from glucose isomerization favours the formation of by-products. The best glucose/NaOH ratio is between 0.5 and 0.1: higher values suppress the OER, while lower values favour the formation of low molecular weight products. The increases of the potential enhance the GO selectivity, nevertheless higher GA selectivity is observed at 0.6 – 0.7V vs SCE, confirmed by catalytic test performed in gluconate (30-35% GA selectivity)

    Scaling up integrated photonic reservoirs towards low-power high-bandwidth computing

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    Atypical developmental trajectories of white matter microstructure in prenatal alcohol exposure: Preliminary evidence from neurite orientation dispersion and density imaging

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    IntroductionFetal alcohol spectrum disorder (FASD), a life-long condition resulting from prenatal alcohol exposure (PAE), is associated with structural brain anomalies and neurobehavioral differences. Evidence from longitudinal neuroimaging suggest trajectories of white matter microstructure maturation are atypical in PAE. We aimed to further characterize longitudinal trajectories of developmental white matter microstructure change in children and adolescents with PAE compared to typically-developing Controls using diffusion-weighted Neurite Orientation Dispersion and Density Imaging (NODDI).Materials and methodsParticipants: Youth with PAE (n = 34) and typically-developing Controls (n = 31) ages 8–17 years at enrollment. Participants underwent formal evaluation of growth and facial dysmorphology. Participants also completed two study visits (17 months apart on average), both of which involved cognitive testing and an MRI scan (data collected on a Siemens Prisma 3 T scanner). Age-related changes in the orientation dispersion index (ODI) and the neurite density index (NDI) were examined across five corpus callosum (CC) regions defined by tractography.ResultsWhile linear trajectories suggested similar overall microstructural integrity in PAE and Controls, analyses of symmetrized percent change (SPC) indicated group differences in the timing and magnitude of age-related increases in ODI (indexing the bending and fanning of axons) in the central region of the CC, with PAE participants demonstrating atypically steep increases in dispersion with age compared to Controls. Participants with PAE also demonstrated greater increases in ODI in the mid posterior CC (trend-level group difference). In addition, SPC in ODI and NDI was differentially correlated with executive function performance for PAE participants and Controls, suggesting an atypical relationship between white matter microstructure maturation and cognitive function in PAE.DiscussionPreliminary findings suggest subtle atypicality in the timing and magnitude of age-related white matter microstructure maturation in PAE compared to typically-developing Controls. These findings add to the existing literature on neurodevelopmental trajectories in PAE and suggest that advanced biophysical diffusion modeling (NODDI) may be sensitive to biologically-meaningful microstructural changes in the CC that are disrupted by PAE. Findings of atypical brain maturation-behavior relationships in PAE highlight the need for further study. Further longitudinal research aimed at characterizing white matter neurodevelopmental trajectories in PAE will be important

    Electrically-evoked responses for retinal prostheses are differentially altered depending on ganglion cell types in outer retinal neurodegeneration caused by Crb1 gene mutation

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    BackgroundMicroelectronic prostheses for artificial vision stimulate neurons surviving outer retinal neurodegeneration such as retinitis pigmentosa (RP). Yet, the quality of prosthetic vision substantially varies across subjects, maybe due to different levels of retinal degeneration and/or distinct genotypes. Although the RP genotypes are remarkably diverse, prosthetic studies have primarily used retinal degeneration (rd) 1 and 10 mice, which both have Pde6b gene mutation. Here, we report the electric responses arising in retinal ganglion cells (RGCs) of the rd8 mouse model which has Crb1 mutation.MethodsWe first investigated age-dependent histological changes of wild-type (wt), rd8, and rd10 mice retinas by H&E staining. Then, we used cell-attached patch clamping to record spiking responses of ON, OFF and direction selective (DS) types of RGCs to a 4-ms-long electric pulse. The electric responses of rd8 RGCs were analyzed in comparison with those of wt RGCs in terms of individual RGC spiking patterns, populational characteristics, and spiking consistency across trials.ResultsIn the histological examination, the rd8 mice showed partial retinal foldings, but the outer nuclear layer thicknesses remained comparable to those of the wt mice, indicating the early-stage of RP. Although spiking patterns of each RGC type seemed similar to those of the wt retinas, correlation levels between electric vs. light response features were different across the two mouse models. For example, in comparisons between light vs. electric response magnitudes, ON/OFF RGCs of the rd8 mice showed the same/opposite correlation polarity with those of wt mice, respectively. Also, the electric response spike counts of DS RGCs in the rd8 retinas showed a positive correlation with their direction selectivity indices (r = 0.40), while those of the wt retinas were negatively correlated (r = −0.90). Lastly, the spiking timing consistencies of late responses were largely decreased in both ON and OFF RGCs in the rd8 than the wt retinas, whereas no significant difference was found across DS RGCs of the two models.ConclusionOur results indicate the electric response features are altered depending on RGC types even from the early-stage RP caused by Crb1 mutation. Given the various degeneration patterns depending on mutation genes, our study suggests the importance of both genotype- and RGC type-dependent analyses for retinal prosthetic research

    Neuroanatomical and gene expression features of the rabbit accessory olfactory system. Implications of pheromone communication in reproductive behaviour and animal physiology

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    Mainly driven by the vomeronasal system (VNS), pheromone communication is involved in many species-specific fundamental innate socio-sexual behaviors such as mating and fighting, which are essential for animal reproduction and survival. Rabbits are a unique model for studying chemocommunication due to the discovery of the rabbit mammary pheromone, but paradoxically there has been a lack of knowledge regarding its VNS pathway. In this work, we aim at filling this gap by approaching the system from an integrative point of view, providing extensive anatomical and genomic data of the rabbit VNS, as well as pheromone-mediated reproductive and behavioural studies. Our results build strong foundation for further translational studies which aim at implementing the use of pheromones to improve animal production and welfare

    neuroAIx-Framework: design of future neuroscience simulation systems exhibiting execution of the cortical microcircuit model 20× faster than biological real-time

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    IntroductionResearch in the field of computational neuroscience relies on highly capable simulation platforms. With real-time capabilities surpassed for established models like the cortical microcircuit, it is time to conceive next-generation systems: neuroscience simulators providing significant acceleration, even for larger networks with natural density, biologically plausible multi-compartment models and the modeling of long-term and structural plasticity.MethodsStressing the need for agility to adapt to new concepts or findings in the domain of neuroscience, we have developed the neuroAIx-Framework consisting of an empirical modeling tool, a virtual prototype, and a cluster of FPGA boards. This framework is designed to support and accelerate the continuous development of such platforms driven by new insights in neuroscience.ResultsBased on design space explorations using this framework, we devised and realized an FPGA cluster consisting of 35 NetFPGA SUME boards.DiscussionThis system functions as an evaluation platform for our framework. At the same time, it resulted in a fully deterministic neuroscience simulation system surpassing the state of the art in both performance and energy efficiency. It is capable of simulating the microcircuit with 20× acceleration compared to biological real-time and achieves an energy efficiency of 48nJ per synaptic event

    Decoding spatial location of attended audio-visual stimulus with EEG and fNIRS

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    When analyzing complex scenes, humans often focus their attention on an object at a particular spatial location in the presence of background noises and irrelevant visual objects. The ability to decode the attended spatial location would facilitate brain computer interfaces (BCI) for complex scene analysis. Here, we tested two different neuroimaging technologies and investigated their capability to decode audio-visual spatial attention in the presence of competing stimuli from multiple locations. For functional near-infrared spectroscopy (fNIRS), we targeted dorsal frontoparietal network including frontal eye field (FEF) and intra-parietal sulcus (IPS) as well as superior temporal gyrus/planum temporal (STG/PT). They all were shown in previous functional magnetic resonance imaging (fMRI) studies to be activated by auditory, visual, or audio-visual spatial tasks. We found that fNIRS provides robust decoding of attended spatial locations for most participants and correlates with behavioral performance. Moreover, we found that FEF makes a large contribution to decoding performance. Surprisingly, the performance was significantly above chance level 1s after cue onset, which is well before the peak of the fNIRS response. For electroencephalography (EEG), while there are several successful EEG-based algorithms, to date, all of them focused exclusively on auditory modality where eye-related artifacts are minimized or controlled. Successful integration into a more ecological typical usage requires careful consideration for eye-related artifacts which are inevitable. We showed that fast and reliable decoding can be done with or without ocular-removal algorithm. Our results show that EEG and fNIRS are promising platforms for compact, wearable technologies that could be applied to decode attended spatial location and reveal contributions of specific brain regions during complex scene analysis
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