ResearchPad - neuronal-dendrites https://www.researchpad.co Default RSS Feed en-us © 2020 Newgen KnowledgeWorks <![CDATA[Low-rate firing limit for neurons with axon, soma and dendrites driven by spatially distributed stochastic synapses]]> https://www.researchpad.co/article/elastic_article_13830 Neurons are extended cells with multiple branching dendrites, a cell body and an axon. In an active neuronal network, neurons receive vast numbers of incoming synaptic pulses throughout their dendrites and cell body that each exhibit significant variability in amplitude and arrival time. The resulting synaptic input causes voltage fluctuations throughout their structure that evolve in space and time. The dynamics of how these signals are integrated and how they ultimately trigger outgoing spikes have been modelled extensively since the late 1960s. However, until relatively recently the majority of the mathematical formulae describing how fluctuating synaptic drive triggers action potentials have been applicable only for small neurons with the dendritic and axonal structure ignored. This has been largely due to the mathematical complexity of including the effects of spatially distributed synaptic input. Here we show that in a physiologically relevant, low-firing-rate regime, an approximate level-crossing approach can be used to provide an estimate for the neuronal firing rate even when the dendrites and axons are included. We illustrate this approach using basic neuronal morphologies that capture the fundamentals of neuronal structure. Though the models are simple, these preliminary results show that it is possible to obtain useful formulae that capture the effects of spatially distributed synaptic drive. The generality of these results suggests they will provide a mathematical framework for future studies that might require the structure of neurons to be taken into account, such as the effect of electrical fields or multiple synaptic input streams that target distinct spatial domains of cortical pyramidal cells.

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<![CDATA[An electrodiffusive, ion conserving Pinsky-Rinzel model with homeostatic mechanisms]]> https://www.researchpad.co/article/elastic_article_7780 Neurons generate their electrical signals by letting ions pass through their membranes. Despite this fact, most models of neurons apply the simplifying assumption that ion concentrations remain effectively constant during neural activity. This assumption is often quite good, as neurons contain a set of homeostatic mechanisms that make sure that ion concentrations vary quite little under normal circumstances. However, under some conditions, these mechanisms can fail, and ion concentrations can vary quite dramatically. Standard models are thus not able to simulate such conditions. Here, we present what to our knowledge is the first multicompartmental neuron model that accounts for ion concentration variations in a way that ensures complete and consistent ion concentration and charge conservation. In this work, we use the model to explore under which activity conditions the ion concentration variations become important for predicting the neurodynamics. We expect the model to be of great value for the field of neuroscience, as it can be used to simulate a range of pathological conditions, such as spreading depression or epilepsy, which are associated with large changes in extracellular ion concentrations.

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<![CDATA[Tuft dendrites of pyramidal neurons operate as feedback-modulated functional subunits]]> https://www.researchpad.co/article/5c897706d5eed0c4847d22c8

Dendrites of pyramidal cells exhibit complex morphologies and contain a variety of ionic conductances, which generate non-trivial integrative properties. Basal and proximal apical dendrites have been shown to function as independent computational subunits within a two-layer feedforward processing scheme. The outputs of the subunits are linearly summed and passed through a final non-linearity. It is an open question whether this mathematical abstraction can be applied to apical tuft dendrites as well. Using a detailed compartmental model of CA1 pyramidal neurons and a novel theoretical framework based on iso-response methods, we first show that somatic sub-threshold responses to brief synaptic inputs cannot be described by a two-layer feedforward model. Then, we relax the core assumption of subunit independence and introduce non-linear feedback from the output layer to the subunit inputs. We find that additive feedback alone explains the somatic responses to synaptic inputs to most of the branches in the apical tuft. Individual dendritic branches bidirectionally modulate the thresholds of their input-output curves without significantly changing the gains. In contrast to these findings for precisely timed inputs, we show that neuronal computations based on firing rates can be accurately described by purely feedforward two-layer models. Our findings support the view that dendrites of pyramidal neurons possess non-linear analog processing capabilities that critically depend on the location of synaptic inputs. The iso-response framework proposed in this computational study is highly efficient and could be directly applied to biological neurons.

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<![CDATA[Population dynamics and entrainment of basal ganglia pacemakers are shaped by their dendritic arbors]]> https://www.researchpad.co/article/5c65dcf2d5eed0c484dec628

The theory of phase oscillators is an essential tool for understanding population dynamics of pacemaking neurons. GABAergic pacemakers in the substantia nigra pars reticulata (SNr), a main basal ganglia (BG) output nucleus, receive inputs from the direct and indirect pathways at distal and proximal regions of their dendritic arbors, respectively. We combine theory, optogenetic stimulation and electrophysiological experiments in acute brain slices to ask how dendritic properties impact the propensity of the various inputs, arriving at different locations along the dendrite, to recruit or entrain SNr pacemakers. By combining cable theory with sinusoidally-modulated optogenetic activation of either proximal somatodendritic regions or the entire somatodendritic arbor of SNr neurons, we construct an analytical model that accurately fits the empirically measured somatic current response to inputs arising from illuminating the soma and various portions of the dendritic field. We show that the extent of the dendritic tree that is illuminated generates measurable and systematic differences in the pacemaker’s phase response curve (PRC), causing a shift in its peak. Finally, we show that the divergent PRCs correctly predict differences in two major features of the collective dynamics of SNr neurons: the fidelity of population responses to sudden step-like changes in inputs; and the phase latency at which SNr neurons are entrained by rhythmic stimulation, which can occur in the BG under both physiological and pathophysiological conditions. Our novel method generates measurable and physiologically meaningful spatial effects, and provides the first empirical demonstration of how the collective responses of SNr pacemakers are determined by the transmission properties of their dendrites. SNr dendrites may serve to delay distal striatal inputs so that they impinge on the spike initiation zone simultaneously with pallidal and subthalamic inputs in order to guarantee a fair competition between the influence of the monosynaptic direct- and polysynaptic indirect pathways.

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<![CDATA[The primate-specific peptide Y-P30 regulates morphological maturation of neocortical dendritic spines]]> https://www.researchpad.co/article/5c6dca0bd5eed0c48452a6fd

The 30-amino acid peptide Y-P30 corresponds to the N-terminus of the primate-specific, sweat gland-derived dermcidin prepropeptide. Previous work has revealed that Y-P30 enhances the interaction of pleiotrophin and syndecans-2/3, and thus represents a natural ligand to study this signaling pathway. In immature neurons, Y-P30 activates the c-Src and p42/44 ERK kinase pathway, increases the amount of F-actin in axonal growth cones, and promotes neuronal survival, cell migration and axonal elongation. The action of Y-P30 on axonal growth requires syndecan-3 and heparan sulfate side chains. Whether Y-P30 has the potential to influence dendrites and dendritic protrusions has not been explored. The latter is suggested by the observations that syndecan-2 expression increases during postnatal development, that syndecan-2 becomes enriched in dendritic spines, and that overexpression of syndecan-2 in immature neurons results in a premature morphological maturation of dendritic spines. Here, analysing rat cortical pyramidal and non-pyramidal neurons in organotypic cultures, we show that Y-P30 does not alter the development of the dendritic arborization patterns. However, Y-P30 treatment decreases the density of apical, but not basal dendritic protrusions at the expense of the filopodia. Analysis of spine morphology revealed an unchanged mushroom/stubby-to-thin spine ratio and a shortening of the longest decile of dendritic protrusions. Whole-cell recordings from cortical principal neurons in dissociated cultures grown in the presence of Y-P30 demonstrated a decrease in the frequency of glutamatergic mEPSCs. Despite these differences in protrusion morphology and synaptic transmission, the latter likely attributable to presynaptic effects, calcium event rate and amplitude recorded in pyramidal neurons in organotypic cultures were not altered by Y-P30 treatment. Together, our data suggest that Y-P30 has the capacity to decelerate spinogenesis and to promote morphological, but not synaptic, maturation of dendritic protrusions.

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<![CDATA[Conserved regulation of neurodevelopmental processes and behavior by FoxP in Drosophila]]> https://www.researchpad.co/article/5c6c75bdd5eed0c4843d00af

FOXP proteins form a subfamily of evolutionarily conserved transcription factors involved in the development and functioning of several tissues, including the central nervous system. In humans, mutations in FOXP1 and FOXP2 have been implicated in cognitive deficits including intellectual disability and speech disorders. Drosophila exhibits a single ortholog, called FoxP, but due to a lack of characterized mutants, our understanding of the gene remains poor. Here we show that the dimerization property required for mammalian FOXP function is conserved in Drosophila. In flies, FoxP is enriched in the adult brain, showing strong expression in ~1000 neurons of cholinergic, glutamatergic and GABAergic nature. We generate Drosophila loss-of-function mutants and UAS-FoxP transgenic lines for ectopic expression, and use them to characterize FoxP function in the nervous system. At the cellular level, we demonstrate that Drosophila FoxP is required in larvae for synaptic morphogenesis at axonal terminals of the neuromuscular junction and for dendrite development of dorsal multidendritic sensory neurons. In the developing brain, we find that FoxP plays important roles in α-lobe mushroom body formation. Finally, at a behavioral level, we show that Drosophila FoxP is important for locomotion, habituation learning and social space behavior of adult flies. Our work shows that Drosophila FoxP is important for regulating several neurodevelopmental processes and behaviors that are related to human disease or vertebrate disease model phenotypes. This suggests a high degree of functional conservation with vertebrate FOXP orthologues and established flies as a model system for understanding FOXP related pathologies.

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<![CDATA[Exploring the effects of electrospun fiber surface nanotopography on neurite outgrowth and branching in neuron cultures]]> https://www.researchpad.co/article/5c61e8c9d5eed0c48496f18d

Three aligned, electrospun fiber scaffolds with unique surface features were created from poly-L-lactic acid (PLLA). Fibers without surface nanotopography (smooth fibers), fibers with surface divots (shallow pits), and fibers with surface pits (deeper pits) were fabricated, and fiber alignment, diameter, and density were characterized using scanning electron microscopy (SEM). Whole dorsal root ganglia (DRG) were isolated from rats and placed onto uncoated fibers or fibers coated with laminin. On uncoated fibers, neurite outgrowth was restricted by fibers displaying divoted or pitted nanotopography when compared to neurite outgrowth on smooth fibers. However, neurites extending from whole DRG cultured on laminin-coated fibers were not restricted by divoted or pitted surface nanotopography. Thus, neurites extending on laminin-coated fibers were able to extend long neurites even in the presence of surface divots or pits. To further explore this result, individual neurons isolated from dissociated DRG were seeded onto laminin-coated smooth, pitted, or divoted fibers. Interestingly, neurons on pitted or divoted fibers exhibited a 1.5-fold increase in total neurite length, and a 2.3 or 2.7-fold increase in neurite branching compared to neurons on smooth fibers, respectively. Based on these findings, we conclude that fiber roughness in the form of pits or divots can promote extension and branching of long neurites along aligned electrospun fibers in the presence of an extracellular matrix protein coating. Thus, aligned, electrospun fibers can be crafted to not only direct the extension of axons but to induce unique branching morphologies.

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<![CDATA[A compact holographic projector module for high-resolution 3D multi-site two-photon photostimulation]]> https://www.researchpad.co/article/5c58d62cd5eed0c484031834

Patterned two-photon (2P) photolysis via holographic illumination is a powerful method to investigate neuronal function because of its capability to emulate multiple synaptic inputs in three dimensions (3D) simultaneously. However, like any optical system, holographic projectors have a finite space-bandwidth product that restricts the spatial range of patterned illumination or field-of-view (FOV) for a desired resolution. Such trade-off between holographic FOV and resolution restricts the coverage within a limited domain of the neuron’s dendritic tree to perform highly resolved patterned 2P photolysis on individual spines. Here, we integrate a holographic projector into a commercial 2P galvanometer-based 2D scanning microscope with an uncaging unit and extend the accessible holographic FOV by using the galvanometer scanning mirrors to reposition the holographic FOV arbitrarily across the imaging FOV. The projector system utilizes the microscope’s built-in imaging functions. Stimulation positions can be selected from within an acquired 3D image stack (the volume-of-interest, VOI) and the holographic projector then generates 3D illumination patterns with multiple uncaging foci. The imaging FOV of our system is 800×800 μm2 within which a holographic VOI of 70×70×70 μm3 can be chosen at arbitrary positions and also moved during experiments without moving the sample. We describe the design and alignment protocol as well as the custom software plugin that controls the 3D positioning of stimulation sites. We demonstrate the neurobiological application of the system by simultaneously uncaging glutamate at multiple spines within dendritic domains and consequently observing summation of postsynaptic potentials at the soma, eventually resulting in action potentials. At the same time, it is possible to perform two-photon Ca2+ imaging in 2D in the dendrite and thus to monitor synaptic Ca2+ entry in selected spines and also local regenerative events such as dendritic action potentials.

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<![CDATA[Different operators and histologic techniques in the assessment of germinal center-like structures in primary Sjögren’s syndrome minor salivary glands]]> https://www.researchpad.co/article/5c644913d5eed0c484c2f56d

Objective

A standardization of minor salivary gland (MSG) histopathology in primary Sjögren’s syndrome (pSS) has been recently proposed. Although there is strong agreement that germinal center (GC)-like structures should be routinely identified, due to their prognostic value, a consensus regarding the best protocol is still lacking. Aim of this study was to compare the performance of different histological techniques and operators to identify GC-like structures in pSS MSGs. MSG biopsies from 50 pSS patients were studied.

Methods

Three blinded operators (one pathologist and two rheumatologists with different years of experience in pSS MSG assessment) assessed 50 MSGs of which one slide was stained with haematoxylin and eosin (H&E) and consecutive slides were processed to investigate CD3/CD20, CD21 and Bcl-6 expression.

Results

By assessing 225 foci, the best agreement was between H&E-stained sections evaluated by the rheumatologist with more years of experience in pSS MSG assessment and CD3/CD20 segregation. In the foci with CD21 positivity, the agreement further increased. Bcl-6- foci could display a GC, detected with other staining, but not vice versa.

Conclusion

GC assessment on H&E-stained sections should be performed with caution, being operator-dependent. The combination of H&E with CD3/CD20 and CD21 staining should be recommended as it is reliable, feasible, able to overcome the bias of operator experience and easily transferrable into routine practice.

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<![CDATA[Neuroprotective and neuroregenerative effects of CRMP-5 on retinal ganglion cells in an experimental in vivo and in vitro model of glaucoma]]> https://www.researchpad.co/article/5c521853d5eed0c484797c19

Purpose

To analyze the potential neuro-protective and neuro-regenerative effects of Collapsin-response-mediator-protein-5 (CRMP-5) on retinal ganglion cells (RGCs) using in vitro and in vivo animal models of glaucoma.

Methods

Elevated intraocular pressure (IOP) was induced in adult female Sprague-Dawley (SD) rats by cauterization of three episcleral veins. Changes in CRMP-5 expression within the retinal proteome were analyzed via label-free mass spectrometry. In vitro, retinal explants were cultured under elevated pressure (60 mmHg) within a high-pressure incubation chamber with and without addition of different concentrations of CRMP-5 (4 μg/l, 200 μg/l and 400 μg/l). In addition, retinal explants were cultured under regenerative conditions with and without application of 200 μg/l CRMP-5 after performing an optic nerve crush (ONC). Thirdly, an antibody against Protein Kinase B (PKB) was added to examine the possible effects of CRMP-5. RGC count was performed. Number and length of the axons were determined and compared. To undermine a signal-transduction pathway via CRMP-5 and PKB microarray and immunohistochemistry were performed.

Results

CRMP-5 was downregulated threefold in animals showing chronically elevated IOP. The addition of CRMP-5 to retinal culture significantly increased RGC numbers under pressure in a dose-dependent manner and increased and elongated outgrowing axons in retinal explants significantly which could be blocked by PKB. Especially the number of neurites longer than 400 μm significantly increased after application of CRMP-5. CRMP-5 as well as PKB were detected higher in the experimental than in the control group.

Conclusion

CRMP-5 seems to play an important role in an animal model of glaucoma. Addition of CRMP-5 exerts neuro-protective and neuro-regenerative effects in vitro. This effect could be mediated via activation of PKB affecting intra-cellular apoptosis pathways.

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<![CDATA[Site-specific HNK-1 epitope on alternatively spliced fibronectin type-III repeats in tenascin-C promotes neurite outgrowth of hippocampal neurons through contactin-1]]> https://www.researchpad.co/article/5c40f81fd5eed0c48438711e

The human natural killer-1 (HNK-1) carbohydrate epitope, composed of a unique sulfated trisaccharide (HSO3–3GlcAβ1–3Galβ1–4GlcNAc-R), is highly expressed during brain development and regulates higher brain function. However, it remains unclear which glycoprotein carries the HNK-1 epitope in the embryonic brain and the functional role it plays. Here, we showed that one of the major HNK-1 carrier proteins in the embryonic brain is tenascin-C (TNC), an extracellular matrix protein that regulates neurite outgrowth by interacting with the GPI-anchored protein contactin-1 (CNTN). Because the alternatively spliced fibronectin type-III (FNIII) repeats in TNC give rise to many isoforms and affect neuronal function, we evaluated neurite outgrowth of primary hippocampal neurons on purified recombinant FNIII repeats with or without the HNK-1 epitope as a substrate. We found that the presence of the HNK-1 epitope on the C domain of TNC promoted neurite outgrowth, and that this signal was mediated by CNTN, which is an HNK-1-expressing neuronal receptor. The neurite-promoting activity of the HNK-1 epitope on TNC required neuronal HNK-1 expression, which was defective in neurons lacking the glucuronyltransferases GlcAT-P and GlcAT-S. These results suggest that the HNK-1 epitope is a key modifier of TNC and CNTN in the regulation of embryonic brain development.

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<![CDATA[AMPK signaling linked to the schizophrenia-associated 1q21.1 deletion is required for neuronal and sleep maintenance]]> https://www.researchpad.co/article/5c23f31ad5eed0c48404a683

The human 1q21.1 deletion of ten genes is associated with increased risk of schizophrenia. This deletion involves the β-subunit of the AMP-activated protein kinase (AMPK) complex, a key energy sensor in the cell. Although neurons have a high demand for energy and low capacity to store nutrients, the role of AMPK in neuronal physiology is poorly defined. Here we show that AMPK is important in the nervous system for maintaining neuronal integrity and for stress survival and longevity in Drosophila. To understand the impact of this signaling system on behavior and its potential contribution to the 1q21.1 deletion syndrome, we focused on sleep, an important role of which is proposed to be the reestablishment of neuronal energy levels that are diminished during energy-demanding wakefulness. Sleep disturbances are one of the most common problems affecting individuals with psychiatric disorders. We show that AMPK is required for maintenance of proper sleep architecture and for sleep recovery following sleep deprivation. Neuronal AMPKβ loss specifically leads to sleep fragmentation and causes dysregulation of genes believed to play a role in sleep homeostasis. Our data also suggest that AMPKβ loss may contribute to the increased risk of developing mental disorders and sleep disturbances associated with the human 1q21.1 deletion.

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<![CDATA[Using computational models to predict in vivo synaptic inputs to interneuron specific 3 (IS3) cells of CA1 hippocampus that also allow their recruitment during rhythmic states]]> https://www.researchpad.co/article/5c3e50b5d5eed0c484d84993

Brain coding strategies are enabled by the balance of synaptic inputs that individual neurons receive as determined by the networks in which they reside. Inhibitory cell types contribute to brain function in distinct ways but recording from specific, inhibitory cell types during behaviour to determine their contributions is highly challenging. In particular, the in vivo activities of vasoactive intestinal peptide-expressing interneuron specific 3 (IS3) cells in the hippocampus that only target other inhibitory cells are unknown at present. We perform a massive, computational exploration of possible synaptic inputs to IS3 cells using multi-compartment models and optimized synaptic parameters. We find that asynchronous, in vivo-like states that are sensitive to additional theta-timed inputs (8 Hz) exist when excitatory and inhibitory synaptic conductances are approximately equally balanced and with low numbers of activated synapses receiving correlated inputs. Specifically, under these balanced conditions, the input resistance is larger with higher mean spike firing rates relative to other activated synaptic conditions investigated. Incoming theta-timed inputs result in strongly increased spectral power relative to baseline. Thus, using a generally applicable computational approach we predict the existence and features of background, balanced states in hippocampal circuits.

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<![CDATA[Function and energy consumption constrain neuronal biophysics in a canonical computation: Coincidence detection]]> https://www.researchpad.co/article/5c12cf09d5eed0c484913d9f

Neural morphology and membrane properties vary greatly between cell types in the nervous system. The computations and local circuit connectivity that neurons support are thought to be the key factors constraining the cells’ biophysical properties. Nevertheless, additional constraints can be expected to further shape neuronal design. Here, we focus on a particularly energy-intense system (as indicated by metabolic markers): principal neurons in the medial superior olive (MSO) nucleus of the auditory brainstem. Based on a modeling approach, we show that a trade-off between the level of performance of a functionally relevant computation and energy consumption predicts optimal ranges for cell morphology and membrane properties. The biophysical parameters appear most strongly constrained by functional needs, while energy use is minimized as long as function can be maintained. The key factors that determine model performance and energy consumption are 1) the saturation of the synaptic conductance input and 2) the temporal resolution of the postsynaptic signals as they reach the soma, which is largely determined by active membrane properties. MSO cells seem to operate close to pareto optimality, i.e., the trade-off boundary between performance and energy consumption that is formed by the set of optimal models. Good performance for drastically lower costs could in theory be achieved by small neurons without dendrites, as seen in the avian auditory system, pointing to additional constraints for mammalian MSO cells, including their circuit connectivity.

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<![CDATA[The neuroanatomy of the siboglinid Riftia pachyptila highlights sedentarian annelid nervous system evolution]]> https://www.researchpad.co/article/5c1c0ab1d5eed0c4844268d5

Tracing the evolution of the siboglinid group, peculiar group of marine gutless annelids, requires the detailed study of the fragmentarily explored central nervous system of vestimentiferans and other siboglinids. 3D reconstructions of the neuroanatomy of Riftia revealed that the “brain” of adult vestimentiferans is a fusion product of the supraesophageal and subesophageal ganglia. The supraesophageal ganglion-like area contains the following neural structures that are homologous to the annelid elements: the peripheral perikarya of the brain lobes, two main transverse commissures, mushroom-like structures, commissural cell cluster, and the circumesophageal connectives with two roots which give rise to the palp neurites. Three pairs of giant perikarya are located in the supraesophageal ganglion, giving rise to the paired giant axons. The circumesophageal connectives run to the VNC. The subesophageal ganglion-like area contains a tripartite ventral aggregation of perikarya (= the postoral ganglion of the VNC) interconnected by the subenteral commissure. The paired VNC is intraepidermal, not ganglionated over most of its length, associated with the ciliary field, and comprises the giant axons. The pairs of VNC and the giant axons fuse posteriorly. Within siboglinids, the vestimentiferans are distinguished by a large and considerably differentiated brain. This reflects the derived development of the tentacle crown. The tentacles of vestimentiferans are homologous to the annelid palps based on their innervation from the dorsal and ventral roots of the circumesophageal connectives. Neuroanatomy of the vestimentiferan brains is close to the brains of Cirratuliiformia and Spionida/Sabellida, which have several transverse commissures, specific position of the giant somata (if any), and palp nerve roots (if any). The palps and palp neurite roots originally developed in all main annelid clades (basally branching, errantian and sedentarian annelids), show the greatest diversity in their number in sedentarian species. Over the course of evolution of Sedentaria, the number of palps and their nerve roots either dramatically increased (as in vestimentiferan siboglinids) or were lost.

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<![CDATA[microRNA-2110 functions as an onco-suppressor in neuroblastoma by directly targeting Tsukushi]]> https://www.researchpad.co/article/5c1d5bccd5eed0c4846eca00

microRNA-2110 (miR-2110) was previously identified as inducing neurite outgrowth in a neuroblastoma cell lines BE(2)-C, suggesting its differentiation-inducing and oncosuppressive function in neuroblastoma. In this study, we demonstrated that synthetic miR-2110 mimic had a generic effect on reducing cell survival in neuroblastoma cell lines with distinct genetic backgrounds, although the induction of cell differentiation traits varied between cell lines. In investigating the mechanisms underlying such functions of miR-2110, we identified that among its predicted target genes down-regulated by miR-2110, knockdown of Tsukushi (TSKU) expression showed the most potent effect in inducing cell differentiation and reducing cell survival, suggesting that TSKU protein plays a key role in mediating the functions of miR-2110. In investigating the clinical relevance of miR-2110 and TSKU expression in neuroblastoma patients, we found that low tumor miR-2110 levels were significantly correlated with high tumor TSKU mRNA levels, and that both low miR-2110 and high TSKU mRNA levels were significantly correlated with poor patient survival. These findings altogether support the oncosuppressive function of miR-2110 and suggest an important role for miR-2110 and its target TSKU in neuroblastoma tumorigenesis and in determining patient prognosis.

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<![CDATA[Cholinesterase inhibitor rivastigmine enhances nerve growth factor-induced neurite outgrowth in PC12 cells via sigma-1 and sigma-2 receptors]]> https://www.researchpad.co/article/5c215139d5eed0c4843f9398

Rivastigmine (Riv) is a potent and selective cholinesterase (acetylcholinesterase, AChE and butyrylcholinesterase, BuChE) inhibitor developed for the treatment of Alzheimer’s disease (AD). To elucidate whether Riv causes neuronal differentiation, we examined its effect on nerve growth factor (NGF)-induced neurite outgrowth in PC12 cells. At concentrations of 0–100 μM, Riv was non-toxic in PC12 cells. Riv caused dose-dependent (10–100 μM) enhancement of NGF-induced neurite outgrowth, which was completely inhibited by the TrkA antagonist GW-441756. By contrast, Riv-mediated enhancement of neurite outgrowth was not blocked by the acetylcholine receptor antagonists, scopolamine and hexamethonium. However, the sigma-1 receptor (Sig-1R) antagonist NE-100 and sigma-2 receptor (Sig-2R) antagonist SM-21 each blocked about half of the Riv-mediated enhancement of NGF-induced neurite outgrowth. Interestingly, the simultaneous application of NE-100 and SM-21 completely blocked the enhancement of NGF-induced neurite outgrowth by Riv. These findings suggest that both Sig-1R and Sig-2R play important roles in NGF-induced neurite outgrowth through TrkA and that Riv may contribute to neuronal repair via Sig-1R and Sig-2R in AD therapy.

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<![CDATA[Compartment models for the electrical stimulation of retinal bipolar cells]]> https://www.researchpad.co/article/5c215132d5eed0c4843f91fe

Bipolar cells of the retina are among the smallest neurons of the nervous system. For this reason, compared to other neurons, their delay in signaling is minimal. Additionally, the small bipolar cell surface combined with the low membrane conductance causes very little attenuation in the signal from synaptic input to the terminal. The existence of spiking bipolar cells was proven over the last two decades, but until now no complete model including all important ion channel types was published. The present study amends this and analyzes the impact of the number of model compartments on simulation accuracy. Characteristic features like membrane voltages and spike generation were tested and compared for one-, two-, four- and 117-compartment models of a macaque bipolar cell. Although results were independent of the compartment number for low membrane conductances (passive membranes), nonlinear regimes such as spiking required at least a separate axon compartment. At least a four compartment model containing the functionally different segments dendrite, soma, axon and terminal was needed for understanding signaling in spiking bipolar cells. Whereas for intracellular current application models with small numbers of compartments showed quantitatively correct results in many cases, the cell response to extracellular stimulation is sensitive to spatial variation of the electric field and accurate modeling therefore demands for a large number of short compartments even for passive membranes.

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<![CDATA[Hierarchical elimination selection method of dendritic river network generalization]]> https://www.researchpad.co/article/5c0ed773d5eed0c484f1417c

Dendritic river networks are fundamental elements in cartography, and the generalization of these river networks directly influences the quality of cartographic generalization. Automatic selection is a difficult and important process for river generalization that requires the consideration of semantic, geometric, topological, and structural characteristics. However, owing to a lack of effective use of river features, most existing methods lose important spatial distribution characteristics of rivers, thus affecting the selection result. Therefore, a hierarchical elimination selection method of dendritic river networks is proposed that consists of three steps. First, a directed topology tree (DTT) is investigated to realize the organization of river data and the intelligent identification of river structures. Second, based on the “180° hypothesis” and “acute angle hypothesis”, each river is traced in the upstream direction from its estuary to create the stroke connections of dendritic river networks based on a consideration of the river semantics, length, and angle features, and the hierarchical relationships of a dendritic river network are then determined. Finally, by determining the total number of selected rivers, a hierarchical elimination algorithm that accounts for density differences is proposed. The reliability of the proposed method was verified using sample data tests, and the rationality and validity of the method were demonstrated in experiments using actual data.

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<![CDATA[Full reconstruction of large lobula plate tangential cells in Drosophila from a 3D EM dataset]]> https://www.researchpad.co/article/5c08419cd5eed0c484fca32f

With the advent of neurogenetic methods, the neural basis of behavior is presently being analyzed in more and more detail. This is particularly true for visually driven behavior of Drosophila melanogaster where cell-specific driver lines exist that, depending on the combination with appropriate effector genes, allow for targeted recording, silencing and optogenetic stimulation of individual cell-types. Together with detailed connectomic data of large parts of the fly optic lobe, this has recently led to much progress in our understanding of the neural circuits underlying local motion detection. However, how such local information is combined by optic flow sensitive large-field neurons is still incompletely understood. Here, we aim to fill this gap by a dense reconstruction of lobula plate tangential cells of the fly lobula plate. These neurons collect input from many hundreds of local motion-sensing T4/T5 neurons and connect them to descending neurons or central brain areas. We confirm all basic features of HS and VS cells as published previously from light microscopy. In addition, we identified the dorsal and the ventral centrifugal horizontal, dCH and vCH cell, as well as three VSlike cells, including their distinct dendritic and axonal projection area.

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