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Journal of Neuroscience Methods Feb 2022Since Cajal's visualisations of the synaptic spine, this feature of the neuron has been of interest to neuroscientists and has been investigated usually in reference to...
BACKGROUND
Since Cajal's visualisations of the synaptic spine, this feature of the neuron has been of interest to neuroscientists and has been investigated usually in reference to degeneration or proliferation of dendrites and their neurons. Synaptic spine measurement often forms a critical element of any study investigating neuronal morphology. However, the way researchers have counted spines hasn't changed for almost a century. Some of the currently used legacy methods fail to accommodate obscured spines or factor-in visibility differences between histological stains.
NEW METHOD
Here we investigate the neuronal dendrite and its synaptic spines, and reveal that using confocal or bright-field technologies may in fact obfuscate spine counts. A mathematical model is developed for the distribution of synaptic spines within the rat, that should, by nature of the formula and the impartiality of probability quotients, be applied to estimate the number of synaptic spines across any length of dendrite that has protrusions within any species.
RESULTS
Using this estimation method, we show that, depending on the method of image capture, there are in fact more spines present than typically counted on lengths of dendrite, something that may have biased morphological studies in the past.
COMPARISON WITH EXISTING METHODS
This new estimation method has been collapsed down into an easy-to-use free website. With input of only four fields, we provide the researcher with a more accurate estimation of the amount of spines on a length of dendrite. This was made possible by fluorescing a Golgi stain and comparing two-photon, bright-field and confocal images.
CONCLUSIONS
An easy web-based resource has been made available to use this new method for spine calculation. Using this method improves the validity of spine measurement and provides a means to review previously published work.
Topics: Animals; Dendrites; Dendritic Spines; Neurons; Rats; Staining and Labeling
PubMed: 34952089
DOI: 10.1016/j.jneumeth.2021.109454 -
Methods in Molecular Biology (Clifton,... 2023Neurons are polarized cells whose polarity and morphology rely on the robust localization of cellular organelles and cargo to axons or dendrites. Developing neurons...
Neurons are polarized cells whose polarity and morphology rely on the robust localization of cellular organelles and cargo to axons or dendrites. Developing neurons require an active secretory pathway, which includes the endoplasmic reticulum and Golgi apparatus, to supply membrane and proteins to growing dendrites and axons. In some neurons, a subset of the Golgi called Golgi "outposts" localize to dendrites and contribute to local secretory networks. The movement and positioning of Golgi outposts have been correlated with dendrite branch growth and stabilization as the dendritic arbor is established. Live imaging is essential to capture the dynamic nature of these organelles. Here we outline a protocol to image and quantify Golgi outposts in peripheral sensory neurons in live, intact Drosophila larvae.
Topics: Animals; Drosophila; Dendrites; Golgi Apparatus; Drosophila Proteins; Endoplasmic Reticulum; Sensory Receptor Cells
PubMed: 36512242
DOI: 10.1007/978-1-0716-2639-9_38 -
International Journal of Molecular... Mar 2020Adult neurogenesis occurs in the dentate gyrus (DG) of the hippocampus. New neurons help to counteract the effects of stress and several interventions including...
Adult neurogenesis occurs in the dentate gyrus (DG) of the hippocampus. New neurons help to counteract the effects of stress and several interventions including antidepressant drugs, environmental modifications and internal factors act pro-neurogenic with consequences in the dorsal and ventral DG. Melatonin, the main product synthesized by the pineal gland, induces antidepressant-like effects and modulates several events of the neurogenic process. However, the information related to the capability of melatonin to modulate dendrite maturation and complexity in the dorsal and ventral regions of the DG and their correlation with its antidepressant-like effect is absent. Thus, in this study, we analyzed the impact of melatonin (0, 0.5, 1, 2.5, 5 or 10 mg/kg) administered daily for fourteen days on the number, dendrite complexity and distribution of doublecortin (DCX)-cells in the dorsal-ventral regions of the DG in male Balb/C mice. Doublecortin is a microtubule-associated protein that is expressed during the course of dendritic maturation of newborn neurons. Also, we analyzed the impact of melatonin on despair-like behavior in the forced swim test. We first found a significant increase in the number and higher dendrite complexity, mainly with the doses of 2.5, 5 and 10 mg/kg of melatonin (81%, 122%, 78%). These cells showed more complex dendritic trees in the ventral- and the dorsal- DG. Concomitantly, the doses of 5 and 10 mg/kg of melatonin decreased depressant-like behavior (76%, 82%). Finally, the data corroborate the antidepressant-like effect of melatonin and the increasing number of doublecortin-associated cells. Besides, the data indicate that melatonin favors the number and dendrite complexity of DCX-cells in the dorsal- and ventral- region of the DG, which may explain part of the antidepressant-like effect of melatonin.
Topics: Animals; Antidepressive Agents; Dendrites; Dentate Gyrus; Depression; Doublecortin Domain Proteins; Doublecortin Protein; Hippocampus; Immunohistochemistry; Male; Melatonin; Mice; Mice, Inbred BALB C; Microtubule-Associated Proteins; Neurogenesis; Neuropeptides
PubMed: 32138332
DOI: 10.3390/ijms21051724 -
Current Opinion in Neurobiology Oct 2021This article highlights specific features of biological neurons and their dendritic trees, whose adoption may help advance artificial neural networks used in various... (Review)
Review
This article highlights specific features of biological neurons and their dendritic trees, whose adoption may help advance artificial neural networks used in various machine learning applications. Advancements could take the form of increased computational capabilities and/or reduced power consumption. Proposed features include dendritic anatomy, dendritic nonlinearities, and compartmentalized plasticity rules, all of which shape learning and information processing in biological networks. We discuss the computational benefits provided by these features in biological neurons and suggest ways to adopt them in artificial neurons in order to exploit the respective benefits in machine learning.
Topics: Dendrites; Machine Learning; Models, Neurological; Neural Networks, Computer; Neurons
PubMed: 34087540
DOI: 10.1016/j.conb.2021.04.007 -
Hormones and Behavior Sep 2021Ovarian hormone deprivation is associated with mood disorders, such as depression, and estradiol therapy is significantly more effective than placebos in treating major...
Ovarian hormone deprivation is associated with mood disorders, such as depression, and estradiol therapy is significantly more effective than placebos in treating major depression associated with menopause onset. However, the effect of estradiol on neuronal plasticity and its mechanisms remain to be further elucidated. In this study, behavioral assessments were used to examine the antidepressant effect of estradiol in ovariectomized (OVX) B6.Cg-TgN (Thy-YFP-H)-2Jrs transgenic mice on chronic restraint stress (CRS)-induced dendrite and dendritic spine loss; Yellow fluorescent protein (YFP) is characteristically expressed in excitatory neurons in transgenic mice, and its three-dimensional images were used to evaluate the effect of estradiol on the density of different types of dendritic spines. Quantification and distribution of cofilin1 and p-cofilin1 were determined by qPCR, Western blots, and immunohistochemistry, respectively. The results revealed that treatment with estradiol or clomipramine significantly improved depression-like behaviors. Estradiol treatment also significantly upregulated the dendritic density in all areas examined and increased the density of filopodia-type, thin-type and mushroom-type spines in the hippocampal CA1 and elevated the thin-type and mushroom-type spine density in the PFC. Consistent with these changes, estradiol treatment significantly increased the density of p-cofilin1 immunopositive dendritic spines. Thus, these data reveal a possible estradiol antidepressant mechanism, in that estradiol promoted the phosphorylation of cofilin1 and reduced the loss of dendrites and dendritic spines, which of these dendritic spines include not only immature spines such as filopodia-type, but also mature spines such as mushroom-type, and attenuated the depression-like behavior.
Topics: Animals; Antidepressive Agents; Dendritic Spines; Estradiol; Female; Hippocampus; Mice; Mice, Transgenic
PubMed: 34358948
DOI: 10.1016/j.yhbeh.2021.105040 -
ELife Aug 2023Dendrite morphogenesis is essential for neural circuit formation, yet the molecular mechanisms underlying complex dendrite branching remain elusive. Previous studies on...
Dendrite morphogenesis is essential for neural circuit formation, yet the molecular mechanisms underlying complex dendrite branching remain elusive. Previous studies on the highly branched PVD sensory neuron identified a membrane co-receptor complex that links extracellular signals to intracellular actin remodeling machinery, promoting high-order dendrite branching. In this complex, the claudin-like transmembrane protein HPO-30 recruits the WAVE regulatory complex (WRC) to dendrite branching sites, stimulating the Arp2/3 complex to polymerize actin. We report here our biochemical and structural analysis of this interaction, revealing that the intracellular domain (ICD) of HPO-30 is intrinsically disordered and employs two distinct mechanisms to regulate the actin cytoskeleton. First, HPO-30 ICD binding to the WRC requires dimerization and involves the entire ICD sequence, rather than a short linear peptide motif. This interaction enhances WRC activation by the GTPase Rac1. Second, HPO-30 ICD directly binds to the sides and barbed end of actin filaments. Binding to the barbed end requires ICD dimerization and inhibits both actin polymerization and depolymerization, resembling the actin capping protein CapZ. These dual functions provide an intriguing model of how membrane proteins can integrate distinct mechanisms to fine-tune local actin dynamics.
Topics: Animals; Actins; Actin Cytoskeleton; Carrier Proteins; Actin-Related Protein 2-3 Complex; Membrane Proteins; Caenorhabditis elegans; Dendrites
PubMed: 37555826
DOI: 10.7554/eLife.88492 -
Scientific Reports May 2022We present a new computational framework of neuron growth based on the phase field method and develop an open-source software package called...
We present a new computational framework of neuron growth based on the phase field method and develop an open-source software package called "NeuronGrowth_IGAcollocation". Neurons consist of a cell body, dendrites, and axons. Axons and dendrites are long processes extending from the cell body and enabling information transfer to and from other neurons. There is high variation in neuron morphology based on their location and function, thus increasing the complexity in mathematical modeling of neuron growth. In this paper, we propose a novel phase field model with isogeometric collocation to simulate different stages of neuron growth by considering the effect of tubulin. The stages modeled include lamellipodia formation, initial neurite outgrowth, axon differentiation, and dendrite formation considering the effect of intracellular transport of tubulin on neurite outgrowth. Through comparison with experimental observations, we can demonstrate qualitatively and quantitatively similar reproduction of neuron morphologies at different stages of growth and allow extension towards the formation of neurite networks.
Topics: Axons; Dendrites; Neurites; Neurogenesis; Neurons; Tubulin
PubMed: 35581253
DOI: 10.1038/s41598-022-12073-z -
Cell Feb 2020The mystery of general anesthesia is that it specifically suppresses consciousness by disrupting feedback signaling in the brain, even when feedforward signaling and...
The mystery of general anesthesia is that it specifically suppresses consciousness by disrupting feedback signaling in the brain, even when feedforward signaling and basic neuronal function are left relatively unchanged. The mechanism for such selectiveness is unknown. Here we show that three different anesthetics have the same disruptive influence on signaling along apical dendrites in cortical layer 5 pyramidal neurons in mice. We found that optogenetic depolarization of the distal apical dendrites caused robust spiking at the cell body under awake conditions that was blocked by anesthesia. Moreover, we found that blocking metabotropic glutamate and cholinergic receptors had the same effect on apical dendrite decoupling as anesthesia or inactivation of the higher-order thalamus. If feedback signaling occurs predominantly through apical dendrites, the cellular mechanism we found would explain not only how anesthesia selectively blocks this signaling but also why conscious perception depends on both cortico-cortical and thalamo-cortical connectivity.
Topics: Anesthetics, General; Animals; Cerebral Cortex; Cholinergic Antagonists; Consciousness; Dendrites; Excitatory Amino Acid Antagonists; Feedback, Physiological; Female; Male; Mice; Pyramidal Cells; Synaptic Transmission; Thalamus
PubMed: 32084339
DOI: 10.1016/j.cell.2020.01.024 -
Nature Materials Sep 2022Solid-state Li-ion batteries with lithium anodes offer higher energy densities and are safer than conventional liquid electrolyte-based Li-ion batteries. However, the...
Solid-state Li-ion batteries with lithium anodes offer higher energy densities and are safer than conventional liquid electrolyte-based Li-ion batteries. However, the growth of lithium dendrites across the solid-state electrolyte layer leads to the premature shorting of cells and limits their practical viability. Here, using solid-state Li half-cells with metallic interlayers between a garnet-based lithium-ion conductor and lithium, we show that interfacial void growth precedes dendrite nucleation and growth. Specifically, void growth was observed at a current density of around two-thirds of the critical current density for dendrite growth. Computational calculations reveal that interlayer materials with higher critical current densities for dendrite growth also have the largest thermodynamic and kinetic barriers for lithium vacancy accumulation at their interfaces with lithium. Our results suggest that interfacial modification with suitable metallic interlayers decreases the tendency for void growth and improves dendrite growth tolerance in solid-state electrolytes, even in the absence of high stack pressures.
Topics: Dendrites; Electric Power Supplies; Electrodes; Electrolytes; Lithium
PubMed: 35655030
DOI: 10.1038/s41563-022-01264-8 -
Developmental Biology Jun 2022Many neurons in bilaterian animals are polarized with functionally distinct axons and dendrites. Microtubule polarity, microtubule stability, and the axon initial...
Many neurons in bilaterian animals are polarized with functionally distinct axons and dendrites. Microtubule polarity, microtubule stability, and the axon initial segment (AIS) have all been shown to influence polarized transport in neurons. Each of these cytoskeletal cues could act independently to control axon and dendrite identity, or there could be a hierarchy in which one acts upstream of the others. Here we test the hypothesis that microtubule polarity acts as a master regulator of neuronal polarity by using a Drosophila genetic background in which some dendrites have normal minus-end-out microtubule polarity and others have the axonal plus-end-out polarity. In these mosaic dendrite arbors, we found that ribosomes, which are more abundant in dendrites than axons, were reduced in plus-end-out dendrites, while an axonal cargo was increased. In addition, we determined that microtubule stability was different in plus-end-out and minus-end-out dendrites, with plus-end-out ones having more stable microtubules like axons. Similarly, we found that ectopic diffusion barriers, like those at the AIS, formed at the base of dendrites with plus-end-out regions. Thus, changes in microtubule polarity were sufficient to rearrange other cytoskeletal features associated with neuronal polarization. However, overall neuron shape was maintained with only subtle changes in branching in mosaic arbors. We conclude that microtubule polarity can act upstream of many aspects of intracellular neuronal polarization, but shape is relatively resilient to changes in microtubule polarity in vivo.
Topics: Animals; Axons; Cell Polarity; Dendrites; Drosophila; Microtubules; Neurons
PubMed: 35341730
DOI: 10.1016/j.ydbio.2022.03.009