Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 19.897
Filtrar
1.
J Vis Exp ; (175)2021 09 17.
Artigo em Inglês | MEDLINE | ID: mdl-34605799

RESUMO

The structure of neuronal dendritic trees plays a key role in the integration of synaptic inputs in neurons. Therefore, characterization of the morphology of dendrites is essential for a better understanding of neuronal function. However, the complexity of dendritic trees, both when isolated and especially when located within neuronal networks, has not been completely understood. We developed a new computational tool, SOA (Segmentation and Orientation Analysis), which allows automatic measurement of the orientation of dendritic branches from fluorescence images of 2D neuronal cultures. SOA, written in Python, uses segmentation to distinguish dendritic branches from the image background and accumulates a database on the spatial direction of each branch. The database is then used to calculate morphological parameters such as the directional distribution of dendritic branches in a network and the prevalence of parallel dendritic branch growth. The data obtained can be used to detect structural changes in dendrites in response to neuronal activity and to biological and pharmacological stimuli.


Assuntos
Dendritos , Neurônios
2.
Cells ; 10(10)2021 10 16.
Artigo em Inglês | MEDLINE | ID: mdl-34685757

RESUMO

Neuronal dendrites receive, integrate, and process numerous inputs and therefore serve as the neuron's "antennae". Dendrites display extreme morphological diversity across different neuronal classes to match the neuron's specific functional requirements. Understanding how this structural diversity is specified is therefore important for shedding light on information processing in the healthy and diseased nervous system. Popular models for in vivo studies of dendrite differentiation are the four classes of dendritic arborization (c1da-c4da) neurons of Drosophila larvae with their class-specific dendritic morphologies. Using da neurons, a combination of live-cell imaging and computational approaches have delivered information on the distinct phases and the time course of dendrite development from embryonic stages to the fully developed dendritic tree. With these data, we can start approaching the basic logic behind differential dendrite development. A major role in the definition of neuron-type specific morphologies is played by dynamic actin-rich processes and the regulation of their properties. This review presents the differences in the growth programs leading to morphologically different dendritic trees, with a focus on the key role of actin modulatory proteins. In addition, we summarize requirements and technological progress towards the visualization and manipulation of such actin regulators in vivo.


Assuntos
Actinas/metabolismo , Dendritos/metabolismo , Drosophila/metabolismo , Animais , Diferenciação Celular
3.
Elife ; 102021 10 26.
Artigo em Inglês | MEDLINE | ID: mdl-34698637

RESUMO

The piriform cortex (PCx) is essential for learning of odor information. The current view postulates that odor learning in the PCx is mainly due to plasticity in intracortical (IC) synapses, while odor information from the olfactory bulb carried via the lateral olfactory tract (LOT) is 'hardwired.' Here, we revisit this notion by studying location- and pathway-dependent plasticity rules. We find that in contrast to the prevailing view, synaptic and optogenetically activated LOT synapses undergo strong and robust long-term potentiation (LTP) mediated by only a few local NMDA-spikes delivered at theta frequency, while global spike timing-dependent plasticity (STDP) protocols failed to induce LTP in these distal synapses. In contrast, IC synapses in apical and basal dendrites undergo plasticity with both NMDA-spikes and STDP protocols but to a smaller extent compared with LOT synapses. These results are consistent with a self-potentiating mechanism of odor information via NMDA-spikes that can form branch-specific memory traces of odors that can further associate with contextual IC information via STDP mechanisms to provide cognitive and emotional value to odors.


Assuntos
Dendritos/fisiologia , Camundongos Endogâmicos C57BL/fisiologia , N-Metilaspartato/fisiologia , Plasticidade Neuronal , Bulbo Olfatório/fisiologia , Córtex Piriforme/fisiologia , Ratos Wistar/fisiologia , Animais , Feminino , Masculino , Camundongos , Ratos
5.
Nat Rev Neurosci ; 22(11): 685-702, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34599308

RESUMO

The sympathetic nervous system prepares the body for 'fight or flight' responses and maintains homeostasis during daily activities such as exercise, eating a meal or regulation of body temperature. Sympathetic regulation of bodily functions requires the establishment and refinement of anatomically and functionally precise connections between postganglionic sympathetic neurons and peripheral organs distributed widely throughout the body. Mechanistic studies of key events in the formation of postganglionic sympathetic neurons during embryonic and early postnatal life, including axon growth, target innervation, neuron survival, and dendrite growth and synapse formation, have advanced the understanding of how neuronal development is shaped by interactions with peripheral tissues and organs. Recent progress has also been made in identifying how the cellular and molecular diversity of sympathetic neurons is established to meet the functional demands of peripheral organs. In this Review, we summarize current knowledge of signalling pathways underlying the development of the sympathetic nervous system. These findings have implications for unravelling the contribution of sympathetic dysfunction stemming, in part, from developmental perturbations to the pathophysiology of peripheral neuropathies and cardiovascular and metabolic disorders.


Assuntos
Axônios/fisiologia , Dendritos/fisiologia , Neurônios/fisiologia , Doenças do Sistema Nervoso Periférico/fisiopatologia , Sistema Nervoso Simpático/crescimento & desenvolvimento , Sistema Nervoso Simpático/fisiopatologia , Animais , Axônios/patologia , Dendritos/patologia , Humanos , Plasticidade Neuronal/fisiologia , Neurônios/patologia , Doenças do Sistema Nervoso Periférico/patologia , Sistema Nervoso Simpático/citologia
6.
Eur J Neurosci ; 54(7): 6355-6373, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34510613

RESUMO

Prostaglandin E2 (PGE2) is a bioactive signalling molecule metabolized from the phospholipid membranes by the enzymatic activity of cycloxygenase-2 (COX-2). In the developing brain, COX-2 constitutively regulates the production of PGE2, which is important in neuronal development. However, abnormal COX-2/PGE2 signalling has been linked to neurodevelopmental disorders including autism spectrum disorders (ASDs). We have previously demonstrated that COX-2- -KI mice show autism-related behaviours including social deficits, repetitive behaviours and anxious behaviours. COX-2-deficient mice also have deficits in pathways involved in synaptic transmission and dendritic spine formation. In this study, we use a Golgi-COX staining method to examine sex-dependent differences in dendritic and dendritic spine morphology in neurons of COX-2- -KI mice cerebellum compared with wild-type (WT) matched controls at postnatal day 25 (P25). We show that COX-2- -KI mice have increased dendritic arborization closer to the cell soma and increased dendritic looping. We also observed a sex-dependent effect of the COX-2- -KI on dendritic thickness, dendritic spine density, dendritic spine morphology, and the expression of ß-actin and the actin-binding protein spinophilin. Our findings show that changes in COX-2/PGE2 signalling lead to impaired morphology of dendrites and dendritic spines in a sex-dependant manner and may contribute the pathology of the cerebellum seen in individuals with ASD. This study provides further evidence that the COX-2- -KI mouse model can be used to study a subset of ASD pathologies.


Assuntos
Transtorno do Espectro Autista , Cerebelo , Ciclo-Oxigenase 2 , Animais , Transtorno do Espectro Autista/genética , Ciclo-Oxigenase 2/genética , Dendritos , Espinhas Dendríticas , Dinoprostona , Técnicas de Introdução de Genes , Camundongos , Neurônios
7.
Small ; 17(42): e2103195, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34528386

RESUMO

Aqueous Zn-ion batteries own great potential on next generation wearable batteries due to the high safety and low cost. However, the uncontrollable dendrites growth and the negligible subzero temperature performance impede the batteries practical applications. Herein, it is demonstrated that dimethyl sulfoxide (DMSO) is an effective additive in ZnSO4 electrolyte for side reactions and dendrites suppression by regulating the Zn-ion solvation structure and inducing the Zn2+ to form the more electrochemical stable (002) basal plane, via the higher absorption energy of DMSO with Zn2+ and (002) plane. Moreover, the stable reconstructed hydrogen bonds between DMSO and H2 O dramatically lower the freezing point of the electrolyte, which significantly increases the ionic conductivity and cycling performance of the aqueous batteries at subzero temperatures. As a consequence, the symmetrical Zn/Zn cell can be kept stable for more than 2100 h at 20 °C and 1200 h at -20 °C without dendrite and by-products formation. The Zn/MnO2 batteries can perform steadily for more than 3000 cycles at 20 °C and 300 cycles at -20 °C. This work provides a facile and feasible strategy on designing high performance and dendrite free aqueous Zn-ion batteries for various temperatures.


Assuntos
Compostos de Manganês , Óxidos , Dendritos , Eletrólitos , Temperatura , Zinco
8.
Neuron ; 109(18): 2914-2927.e5, 2021 09 15.
Artigo em Inglês | MEDLINE | ID: mdl-34534454

RESUMO

In the neocortex, subcerebral axonal projections originate largely from layer 5 (L5) extratelencephalic-projecting (ET) neurons. The unique morpho-electric properties of these neurons have been mainly described in rodents, where retrograde tracers or transgenic lines can label them. Similar labeling strategies are infeasible in the human neocortex, rendering the translational relevance of findings in rodents unclear. We leveraged the recent discovery of a transcriptomically defined L5 ET neuron type to study the properties of human L5 ET neurons in neocortical brain slices derived from neurosurgeries. Patch-seq recordings, where transcriptome, physiology, and morphology were assayed from the same cell, revealed many conserved morpho-electric properties of human and rodent L5 ET neurons. Divergent properties were often subtler than differences between L5 cell types within these two species. These data suggest a conserved function of L5 ET neurons in the neocortical hierarchy but also highlight phenotypic divergence possibly related to functional specialization of human neocortex.


Assuntos
Dendritos/fisiologia , Morfogênese/fisiologia , Neocórtex/citologia , Neocórtex/fisiologia , Células Piramidais/fisiologia , Transcriptoma/fisiologia , Potenciais de Ação/fisiologia , Adulto , Animais , Feminino , Humanos , Macaca nemestrina , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Pessoa de Meia-Idade , Técnicas de Cultura de Órgãos , Técnicas de Patch-Clamp/métodos
9.
Elife ; 102021 09 21.
Artigo em Inglês | MEDLINE | ID: mdl-34545811

RESUMO

Activity-driven changes in the neuronal surface glycoproteome are known to occur with synapse formation, plasticity, and related diseases, but their mechanistic basis and significance are unclear. Here, we observed that N-glycans on surface glycoproteins of dendrites shift from immature to mature forms containing sialic acid in response to increased neuronal activation. In exploring the basis of these N-glycosylation alterations, we discovered that they result from the growth and proliferation of Golgi satellites scattered throughout the dendrite. Golgi satellites that formed during neuronal excitation were in close association with endoplasmic reticulum (ER) exit sites and early endosomes and contained glycosylation machinery without the Golgi structural protein, GM130. They functioned as distal glycosylation stations in dendrites, terminally modifying sugars either on newly synthesized glycoproteins passing through the secretory pathway or on surface glycoproteins taken up from the endocytic pathway. These activities led to major changes in the dendritic surface of excited neurons, impacting binding and uptake of lectins, as well as causing functional changes in neurotransmitter receptors such as nicotinic acetylcholine receptors. Neural activity thus boosts the activity of the dendrite's satellite micro-secretory system by redistributing Golgi enzymes involved in glycan modifications into peripheral Golgi satellites. This remodeling of the neuronal surface has potential significance for synaptic plasticity, addiction, and disease.


Assuntos
Dendritos/metabolismo , Complexo de Golgi/metabolismo , Glicoproteínas de Membrana/metabolismo , Animais , Autoantígenos/metabolismo , Proliferação de Células , Retículo Endoplasmático/metabolismo , Glicosilação , Células HEK293 , Humanos , Proteínas de Membrana/metabolismo , Neurônios/metabolismo , Polissacarídeos/metabolismo , Proteoma/metabolismo , Ratos , Receptores Nicotínicos/metabolismo
10.
Cells ; 10(9)2021 09 12.
Artigo em Inglês | MEDLINE | ID: mdl-34572046

RESUMO

The retinas of many species show regional specialisations that are evident in the differences in the processing of visual input from different parts of the visual field. Regional specialisation is thought to reflect an adaptation to the natural visual environment, optical constraints, and lifestyle of the species. Yet, little is known about regional differences in synaptic circuitry. Here, we were interested in the topographical distribution of connexin-36 (Cx36), the major constituent of electrical synapses in the retina. We compared the retinas of mice, rats, and cats to include species with different patterns of regional specialisations in the analysis. First, we used the density of Prox1-immunoreactive amacrine cells as a marker of any regional specialisation, with higher cell density signifying more central regions. Double-labelling experiments showed that Prox1 is expressed in AII amacrine cells in all three species. Interestingly, large Cx36 plaques were attached to about 8-10% of Prox1-positive amacrine cell somata, suggesting the strong electrical coupling of pairs or small clusters of cell bodies. When analysing the regional changes in the volumetric density of Cx36-immunoreactive plaques, we found a tight correlation with the density of Prox1-expressing amacrine cells in the ON, but not in the OFF sublamina in all three species. The results suggest that the relative contribution of electrical synapses to the ON- and OFF-pathways of the retina changes with retinal location, which may contribute to functional ON/OFF asymmetries across the visual field.


Assuntos
Células Amácrinas/fisiologia , Conexinas/metabolismo , Dendritos/fisiologia , Sinapses Elétricas/fisiologia , Junções Comunicantes/fisiologia , Proteínas de Homeodomínio/metabolismo , Retina/fisiologia , Proteínas Supressoras de Tumor/metabolismo , Células Amácrinas/citologia , Animais , Conexinas/genética , Feminino , Proteínas de Homeodomínio/genética , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Ratos , Ratos Wistar , Retina/citologia , Proteínas Supressoras de Tumor/genética
11.
Elife ; 102021 09 07.
Artigo em Inglês | MEDLINE | ID: mdl-34491202

RESUMO

Developing neurons form synapses at a high rate. Synaptic transmission is very energy-demanding and likely requires ATP production by mitochondria nearby. Mitochondria might be targeted to active synapses in young dendrites, but whether such motility regulation mechanisms exist is unclear. We investigated the relationship between mitochondrial motility and neuronal activity in the primary visual cortex of young mice in vivo and in slice cultures. During the first 2 postnatal weeks, mitochondrial motility decreases while the frequency of neuronal activity increases. Global calcium transients do not affect mitochondrial motility. However, individual synaptic transmission events precede local mitochondrial arrest. Pharmacological stimulation of synaptic vesicle release, but not focal glutamate application alone, stops mitochondria, suggesting that an unidentified factor co-released with glutamate is required for mitochondrial arrest. A computational model of synaptic transmission-mediated mitochondrial arrest shows that the developmental increase in synapse number and transmission frequency can contribute substantially to the age-dependent decrease of mitochondrial motility.


Assuntos
Dendritos/metabolismo , Mitocôndrias/fisiologia , Animais , Cálcio/metabolismo , Ácido Glutâmico/metabolismo , Camundongos , Neurônios/fisiologia , Sinapses/fisiologia , Transmissão Sináptica/fisiologia , Vesículas Sinápticas
12.
Elife ; 102021 09 21.
Artigo em Inglês | MEDLINE | ID: mdl-34545809

RESUMO

Nearly 50 different mouse retinal ganglion cell (RGC) types sample the visual scene for distinct features. RGC feature selectivity arises from their synapses with a specific subset of amacrine (AC) and bipolar cell (BC) types, but how RGC dendrites arborize and collect input from these specific subsets remains poorly understood. Here we examine the hypothesis that RGCs employ molecular recognition systems to meet this challenge. By combining calcium imaging and type-specific histological stains, we define a family of circuits that express the recognition molecule Sidekick-1 (Sdk1), which include a novel RGC type (S1-RGC) that responds to local edges. Genetic and physiological studies revealed that Sdk1 loss selectively disrupts S1-RGC visual responses, which result from a loss of excitatory and inhibitory inputs and selective dendritic deficits on this neuron. We conclude that Sdk1 shapes dendrite growth and wiring to help S1-RGCs become feature selective.


Assuntos
Sinalização do Cálcio , Dendritos/metabolismo , Imunoglobulina G/metabolismo , Proteínas de Membrana/metabolismo , Plasticidade Neuronal , Células Ganglionares da Retina/metabolismo , Sinapses/metabolismo , Visão Ocular , Percepção Visual , Animais , Fator II de Transcrição COUP/genética , Fator II de Transcrição COUP/metabolismo , Potenciais Pós-Sinápticos Excitadores , Feminino , Proteínas de Homeodomínio/genética , Proteínas de Homeodomínio/metabolismo , Imunoglobulina G/genética , Potenciais Pós-Sinápticos Inibidores , Masculino , Proteínas de Membrana/genética , Camundongos Knockout , Inibição Neural , Estimulação Luminosa , Sinapses/genética , Fatores de Tempo , Fator de Transcrição Brn-3C/genética , Fator de Transcrição Brn-3C/metabolismo , Vias Visuais/metabolismo
13.
BMC Res Notes ; 14(1): 311, 2021 Aug 14.
Artigo em Inglês | MEDLINE | ID: mdl-34391474

RESUMO

OBJECTIVE: RNA-binding proteins (RBPs) are important regulators of gene expression that influence mRNA splicing, stability, localization, transport, and translational control. In particular, RBPs play an important role in neurons, which have a complex morphology. Previously, we showed that there are many RBPs that play a conserved role in dendrite development in Drosophila dendritic arborization neurons and Caenorhabditis elegans (C. elegans) PVD neurons including the cytoplasmic polyadenylation element binding proteins (CPEBs), Orb in Drosophila and CPB-3 in C. elegans, and the DEAD box RNA helicases, Me31B in Drosophila and CGH-1 in C. elegans. During these studies, we observed that fluorescently-labeled CPB-3 and CGH-1 localize to cytoplasmic particles that are motile, and our research aims to further characterize these RBP-containing particles in live neurons. RESULTS: Here we extend on previous work to show that CPB-3 and CGH-1 localize to motile particles within dendrites that move at a speed consistent with microtubule-based transport. This is consistent with a model in which CPB-3 and CGH-1 influence dendrite development through the transport and localization of their mRNA targets. Moreover, CPB-3 and CGH-1 rarely localize to the same particles suggesting that these RBPs function in discrete ribonucleoprotein particles (RNPs) that may regulate distinct mRNAs.


Assuntos
Proteínas de Caenorhabditis elegans , Caenorhabditis elegans , Animais , Caenorhabditis elegans/genética , Proteínas de Caenorhabditis elegans/genética , Proteínas de Caenorhabditis elegans/metabolismo , Dendritos , RNA Nucleotidiltransferases , Proteínas de Ligação a RNA/genética , Células Receptoras Sensoriais/metabolismo
14.
Neuron ; 109(17): 2727-2739.e3, 2021 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-34380016

RESUMO

Utilizing recent advances in machine learning, we introduce a systematic approach to characterize neurons' input/output (I/O) mapping complexity. Deep neural networks (DNNs) were trained to faithfully replicate the I/O function of various biophysical models of cortical neurons at millisecond (spiking) resolution. A temporally convolutional DNN with five to eight layers was required to capture the I/O mapping of a realistic model of a layer 5 cortical pyramidal cell (L5PC). This DNN generalized well when presented with inputs widely outside the training distribution. When NMDA receptors were removed, a much simpler network (fully connected neural network with one hidden layer) was sufficient to fit the model. Analysis of the DNNs' weight matrices revealed that synaptic integration in dendritic branches could be conceptualized as pattern matching from a set of spatiotemporal templates. This study provides a unified characterization of the computational complexity of single neurons and suggests that cortical networks therefore have a unique architecture, potentially supporting their computational power.


Assuntos
Córtex Cerebral/fisiologia , Aprendizado Profundo , Modelos Neurológicos , Células Piramidais/fisiologia , Córtex Cerebral/citologia , Córtex Cerebral/metabolismo , Dendritos/metabolismo , Dendritos/fisiologia , Humanos , Células Piramidais/metabolismo , Receptores de N-Metil-D-Aspartato/metabolismo
15.
Int J Mol Sci ; 22(15)2021 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-34360985

RESUMO

Neurodevelopmental disorders can derive from a complex combination of genetic variation and environmental pressures on key developmental processes. Despite this complex aetiology, and the equally complex array of syndromes and conditions diagnosed under the heading of neurodevelopmental disorder, there are parallels in the neuropathology of these conditions that suggest overlapping mechanisms of cellular injury and dysfunction. Neuronal arborisation is a process of dendrite and axon extension that is essential for the connectivity between neurons that underlies normal brain function. Disrupted arborisation and synapse formation are commonly reported in neurodevelopmental disorders. Here, we summarise the evidence for disrupted neuronal arborisation in these conditions, focusing primarily on the cortex and hippocampus. In addition, we explore the developmentally specific mechanisms by which neuronal arborisation is regulated. Finally, we discuss key regulators of neuronal arborisation that could link to neurodevelopmental disease and the potential for pharmacological modification of arborisation and the formation of synaptic connections that may provide therapeutic benefit in the future.


Assuntos
Encéfalo/crescimento & desenvolvimento , Transtornos do Neurodesenvolvimento/patologia , Crescimento Neuronal , Animais , Encéfalo/fisiopatologia , Dendritos/metabolismo , Dendritos/patologia , Humanos , Transtornos do Neurodesenvolvimento/tratamento farmacológico , Transtornos do Neurodesenvolvimento/fisiopatologia , Fármacos Neuroprotetores/uso terapêutico
16.
Small ; 17(39): e2103048, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34427378

RESUMO

Water loss of the gel polymer electrolytes (GPEs) and dendrites growth on Zn anode are overriding obstacles to applying flexible zinc-air batteries (ZABs) for wearable electronic devices. Nearly all previous efforts aim at developing novel GPEs with enhanced water retention and therefore elongate their lifespan. Herein, a facile interface engineering strategy is proposed to retard the water loss of GPE from the half-open structured air cathode. In detail, the poly(ethylene vinyl acetate)/carbon powder (PEVA-C) nanofiber composite interface layer with features of hydrophobicity, high conductivity, air permeability, and flexibility are prepared on the carbon cloth and set up between the GPE and electrode. The as-assembled ZAB with simple alkaline PVA GPE exhibits an impressive cycle life of 230 h, which outperforms ZAB without the PEVA-C nanofibers interface layer by 14 times. Additionally, the growth of Zn dendrites can be suppressed due to the tardy water loss of GPE.


Assuntos
Nanofibras , Zinco , Dendritos , Fontes de Energia Elétrica , Água
17.
Development ; 148(17)2021 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-34414407

RESUMO

Reelin is a large secreted glycoprotein that regulates neuronal migration, lamination and establishment of dendritic architecture in the embryonic brain. Reelin expression switches postnatally from Cajal-Retzius cells to interneurons. However, reelin function in interneuron development is still poorly understood. Here, we have investigated the role of reelin in interneuron development in the postnatal neocortex. To preclude early cortical migration defects caused by reelin deficiency, we employed a conditional reelin knockout (RelncKO) mouse to induce postnatal reelin deficiency. Induced reelin deficiency caused dendritic hypertrophy in distal dendritic segments of neuropeptide Y-positive (NPY+) and calretinin-positive (Calr+) interneurons, and in proximal dendritic segments of parvalbumin-positive (Parv+) interneurons. Chronic recombinant Reelin treatment rescued dendritic hypertrophy in Relncko interneurons. Moreover, we provide evidence that RelncKO interneuron hypertrophy is due to presynaptic GABABR dysfunction. Thus, GABABRs in RelncKO interneurons were unable to block N-type (Cav2.2) Ca2+ channels that control neurotransmitter release. Consequently, the excessive Ca2+ influx through AMPA receptors, but not NMDA receptors, caused interneuron dendritic hypertrophy. These findings suggest that reelin acts as a 'stop-growth-signal' for postnatal interneuron maturation.


Assuntos
Moléculas de Adesão Celular Neuronais/metabolismo , Dendritos/metabolismo , Proteínas da Matriz Extracelular/metabolismo , Interneurônios/citologia , Neocórtex/crescimento & desenvolvimento , Proteínas do Tecido Nervoso/metabolismo , Serina Endopeptidases/metabolismo , Animais , Calbindina 2/metabolismo , Cálcio/metabolismo , Moléculas de Adesão Celular Neuronais/deficiência , Moléculas de Adesão Celular Neuronais/farmacologia , Dendritos/efeitos dos fármacos , Proteínas da Matriz Extracelular/deficiência , Proteínas da Matriz Extracelular/farmacologia , Hipertrofia , Interneurônios/efeitos dos fármacos , Interneurônios/metabolismo , Camundongos , Camundongos Knockout , Neocórtex/citologia , Neocórtex/efeitos dos fármacos , Neocórtex/patologia , Proteínas do Tecido Nervoso/deficiência , Proteínas do Tecido Nervoso/farmacologia , Neuropeptídeo Y/metabolismo , Parvalbuminas/metabolismo , Receptores de GABA-B/metabolismo , Receptores de Glutamato/metabolismo , Serina Endopeptidases/deficiência , Serina Endopeptidases/farmacologia
18.
EMBO Rep ; 22(10): e52679, 2021 10 05.
Artigo em Inglês | MEDLINE | ID: mdl-34338441

RESUMO

It has long been thought that microtubule disassembly, one of the earliest cellular events, contributes to neuronal pruning and neurodegeneration in development and disease. However, how microtubule disassembly drives neuronal pruning remains poorly understood. Here, we conduct a systematic investigation of various microtubule-destabilizing factors and identify exchange factor for Arf6 (Efa6) and Stathmin (Stai) as new regulators of dendrite pruning in ddaC sensory neurons during Drosophila metamorphosis. We show that Efa6 is both necessary and sufficient to regulate dendrite pruning. Interestingly, Efa6 and Stai facilitate microtubule turnover and disassembly prior to dendrite pruning without compromising the minus-end-out microtubule orientation in dendrites. Moreover, our pharmacological and genetic manipulations strongly support a key role of microtubule disassembly in promoting dendrite pruning. Thus, this systematic study highlights the importance of two selective microtubule destabilizers in dendrite pruning and substantiates a causal link between microtubule disassembly and neuronal pruning.


Assuntos
Proteínas de Drosophila , Drosophila , Animais , Dendritos , Drosophila/genética , Proteínas de Drosophila/genética , Drosophila melanogaster/genética , Microtúbulos , Plasticidade Neuronal
19.
eNeuro ; 8(5)2021.
Artigo em Inglês | MEDLINE | ID: mdl-34380656

RESUMO

Throughout the nervous system, the organization of excitatory and inhibitory synaptic inputs within a neuron's receptive field shapes its output computation. In some cases, multiple motifs of synaptic organization can contribute to a single computation. Here, we compare two of these mechanisms performed by two morphologically distinct retinal direction-selective ganglion cells (DSGCs): directionally tuned inhibition and spatially offset inhibition. Using drifting stimuli, we found that DSGCs that have asymmetric dendrites exhibited stronger directionally tuned inhibition than symmetric DSGCs. Using stationary stimuli to map receptive fields, we found that DSGCs with both symmetric and asymmetric dendrites exhibited similar spatially offset inhibition. Interestingly, we observed that excitatory and inhibitory synapses for both cell types were locally correlated in strength. This result indicates that in the mouse retina, dendritic morphology influences the amount of tuned inhibition attained through asymmetric wiring but does not dictate the synaptic organization of excitation relative to inhibition.


Assuntos
Células Ganglionares da Retina , Sinapses , Animais , Dendritos , Camundongos , Retina
20.
Neuroinformatics ; 19(4): 703-717, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34342808

RESUMO

Dendrites shape inputs and integration of depolarization that controls neuronal activity in the nervous system. Neuron pathologies can damage dendrite architecture and cause abnormalities in morphologies after injury. Dendrite regeneration can be quantified by various parameters, including total dendrite length and number of dendrite branches using manual or automated image analysis approaches. However, manual quantification is tedious and time consuming and automated approaches are often trained using wildtype neurons, making them poorly suited for analysis of genetically manipulated or injured dendrite arbors. In this study, we tested how well automated image analysis software performed on class IV Drosophila neurons, which have several hundred individual dendrite branches. We applied each software to automatically quantify features of uninjured neurons and neurons that regenerated new dendrites after injury. Regenerated arbors exhibit defects across multiple features of dendrite morphology, which makes them challenging for automated pipelines to analyze. We compared the performances of three automated pipelines against manual quantification using Simple Neurite Tracer in ImageJ: one that is commercially available (Imaris) and two developed by independent research groups (DeTerm and Tireless Tracing Genie). Out of the three software tested, we determined that Imaris is the most efficient at reconstructing dendrite architecture, but does not accurately measure total dendrite length even after intensive manual editing. Imaris outperforms both DeTerm and Tireless Tracing Genie for counting dendrite branches, and is better able to recreate previous conclusions from this same dataset. This thorough comparison of strengths and weaknesses of each software demonstrates their utility for analyzing regenerated neuron phenotypes in future studies.


Assuntos
Dendritos , Drosophila , Animais , Neuritos , Neurônios , Software
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...