共查询到20条相似文献,搜索用时 15 毫秒
1.
Libersat F 《Journal of neurobiology》2005,64(1):11-23
The highly complex geometry of dendritic trees is crucial for neural signal integration and the proper wiring of neuronal circuits. The morphogenesis of dendritic trees is regulated by innate genetic factors, neuronal activity, and external molecular cues. How each of these factors contributes to dendritic maturation has been addressed in studies of the developing nervous systems of animals ranging from insects to mammals. This article reviews our current knowledge and understanding of the role of afferent input in the establishment of the architecture of mature dendritic trees, using insect neurons as models. With these model systems and using quantitative morphometry, it is possible to define the contributions of intrinsic and extrinsic factors in dendritic morphogenesis of identified neurons and to evaluate the impact of dendritic maturation on the integration of identified neurons into functional circuits subserving identified behaviors. The commonly held view of dendritic morphogenesis is that general structural features result from genetic instructions, whereas fine connectivity details rely mostly on substrate interactions and functional activity. During early dendritic maturation, dendritic growth cone formation produces new branches at all dendritic roots. The second phase is growth cone independent and afferent input dependent, during which branching is limited to high order distal dendrites. During the third phase, activity-dependent synaptic maturation occurs with limited or subtle remodeling of branching. 相似文献
2.
Yoonju Kim Sang-Eun Lee Joohyun Park Minhyung Kim Boyoon Lee Daehee Hwang Sunghoe Chang 《The Journal of biological chemistry》2015,290(12):7323-7335
Recent studies have reported conflicting results regarding the role of ARF6 in dendritic spine development, but no clear answer for the controversy has been suggested. We found that ADP-ribosylation factor 6 (ARF6) either positively or negatively regulates dendritic spine formation depending on neuronal maturation and activity. ARF6 activation increased the spine formation in developing neurons, whereas it decreased spine density in mature neurons. Genome-wide microarray analysis revealed that ARF6 activation in each stage leads to opposite patterns of expression of a subset of genes that are involved in neuronal morphology. ARF6-mediated Rac1 activation via the phospholipase D pathway is the coincident factor in both stages, but the antagonistic RhoA pathway becomes involved in the mature stage. Furthermore, blocking neuronal activity in developing neurons using tetrodotoxin or enhancing the activity in mature neurons using picrotoxin or chemical long term potentiation reversed the effect of ARF6 on each stage. Thus, activity-dependent dynamic changes in ARF6-mediated spine structures may play a role in structural plasticity of mature neurons. 相似文献
3.
Gualdoni S Albertinazzi C Corbetta S Valtorta F de Curtis I 《Biology of the cell / under the auspices of the European Cell Biology Organization》2007,99(8):455-464
Background information. Rho family GTPases are required for cytoskeletal reorganization and are considered important for the maturation of neurons. Among these proteins, Rac1 is known to play a crucial role in the regulation of actin dynamics, and a number of studies indicate the involvement of this protein in different steps of vertebrate neuronal maturation. There are two distinct Rac proteins expressed in neurons, namely the ubiquitous Rac1 and the neuron‐specific Rac3. The specific functions of each of these GTPases during early neuronal development are largely unknown. Results. The combination of the knockout of Rac3 with Rac1 down‐regulation by siRNA (small interfering RNA) has been used to show that down‐regulation of Rac1 affects dendritic development in mouse hippocampal neurons, without affecting axons. F‐actin levels are strongly decreased in neuronal growth cones following down‐regulation of Rac1, and time‐lapse analysis indicated that the reduction of Rac1 levels decreases growth‐cone dynamics. Conclusions. These results show that normal levels of endogenous Rac1 activity are critical for early dendritic development, whereas dendritic outgrowth is not affected in hippocampal neurons from Rac3‐null mice. On the other hand, early axonal development appears normal after Rac1 down‐regulation. Our findings also suggest that the initial establishment of neuronal polarity is not affected by Rac1 down‐regulation. 相似文献
4.
Krivosheya D Tapia L Levinson JN Huang K Kang Y Hines R Ting AK Craig AM Mei L Bamji SX El-Husseini A 《The Journal of biological chemistry》2008,283(47):32944-32956
Perturbations in neuregulin-1 (NRG1)/ErbB4 function have been associated with schizophrenia. Affected patients exhibit altered levels of these proteins and display hypofunction of glutamatergic synapses as well as altered neuronal circuitry. However, the role of NRG1/ErbB4 in regulating synapse maturation and neuronal process formation has not been extensively examined. Here we demonstrate that ErbB4 is expressed in inhibitory interneurons at both excitatory and inhibitory postsynaptic sites. Overexpression of ErbB4 postsynaptically enhances size but not number of presynaptic inputs. Conversely, knockdown of ErbB4 using shRNA decreases the size of presynaptic inputs, demonstrating a specific role for endogenous ErbB4 in synapse maturation. Using ErbB4 mutant constructs, we demonstrate that ErbB4-mediated synapse maturation requires its extracellular domain, whereas its tyrosine kinase activity is dispensable for this process. We also demonstrate that depletion of ErbB4 decreases the number of primary neurites and that stimulation of ErbB4 using a soluble form of NRG1 results in exuberant dendritic arborization through activation of the tyrosine kinase domain of ErbB4 and the phosphoinositide 3-kinase pathway. These findings demonstrate that NRG1/ErbB4 signaling differentially regulates synapse maturation and dendritic morphology via two distinct mechanisms involving trans-synaptic signaling and tyrosine kinase activity, respectively. 相似文献
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6.
The dendritic trees of different neuronal types display an astonishing diversity in structure and function. How this diversity is generated remains incompletely understood. However, recent studies have revealed some of the underlying mechanisms by which intrinsic programs of cell-type specification and extrinsic factors exert their effects on the dendritic cytoskeleton to regulate patterns of growth and branching. 相似文献
7.
Most neurons have elaborate dendritic trees that receive tens of thousands of synaptic inputs. Because postsynaptic responses to individual synaptic events are usually small and transient, the integration of many synaptic responses is needed to depolarize most neurons to action potential threshold. Over the past decade, advances in electrical and optical recording techniques have led to new insights into how synaptic responses propagate and interact within dendritic trees. In addition to their passive electrical and morphological properties, dendrites express active conductances that shape individual synaptic responses and influence synaptic integration locally within dendrites. Dendritic voltage-gated Na(+) and Ca(2+) channels support action potential backpropagation into the dendritic tree and local initiation of dendritic spikes, whereas K(+) conductances act to dampen dendritic excitability. While all dendrites investigated to date express active conductances, different neuronal types show specific patterns of dendritic channel expression leading to cell-specific differences in the way synaptic responses are integrated within dendritic trees. This review explores the way active and passive dendritic properties shape synaptic responses in the dendrites of central neurons, and emphasizes their role in synaptic integration. 相似文献
8.
Peter Verstraelen Isabel Pintelon Rony Nuydens Frans Cornelissen Theo Meert Jean-Pierre Timmermans 《Cellular and molecular neurobiology》2014,34(5):757-776
Mental disorders, such as schizophrenia or Alzheimer’s disease, are associated with impaired synaptogenesis and/or synaptic communication. During development, neurons assemble into neuronal networks, the primary supracellular mediators of information processing. In addition to the orchestrated activation of genetic programs, spontaneous electrical activity and associated calcium signaling have been shown to be critically involved in the maturation of such neuronal networks. We established an in vitro model that recapitulates the maturation of neuronal networks, including spontaneous electrical activity. Upon plating, mouse primary hippocampal neurons grow neurites and interconnect via synapses to form a dish-wide neuronal network. Via live cell calcium imaging, we identified a limited period of time in which the spontaneous activity synchronizes across neurons, indicative of the formation of a functional network. After establishment of network activity, the neurons grow dendritic spines, the density of which was used as a morphological readout for neuronal maturity and connectivity. Hence, quantification of neurite outgrowth, synapse density, spontaneous neuronal activity, and dendritic spine density allowed to study neuronal network maturation from the day of plating until the presence of mature neuronal networks. Via acute pharmacological intervention, we show that synchronized network activity is mediated by the NMDA-R. The balance between kynurenic and quinolinic acid, both neuro-active intermediates in the tryptophan/kynurenine pathway, was shown to be decisive for the maintenance of network activity. Chronic modulation of the neurotrophic support influenced the network formation and revealed the extreme sensitivity of calcium imaging to detect subtle alterations in neuronal physiology. Given the reproducible cultivation in a 96-well setup in combination with fully automated analysis of the calcium recordings, this approach can be used to build a high-content screening assay usable for neurotoxicity screening, target identification/validation, or phenotypic drug screening. 相似文献
9.
Active mechanisms of re-orientation are necessary to maintain the verticality of tree stems. They are achieved through the production of reaction wood, associated with circumferential variations of three factors related to cambial activity: maturation strain, longitudinal modulus of elasticity (MOE) and eccentric growth. These factors were measured on 17 mature trees from different botanical families and geographical locations. Various patterns of circumferential variation of these factors were identified. A biomechanical analysis based on beam theory was performed to quantify the individual impact of each factor. The main factor of re-orientation is the circumferential variation of maturation strains. However, this factor alone explains only 57% of the re-orientations. Other factors also have an effect through their interaction with maturation strains. Eccentric growth is generally associated with heterogeneity of maturation strains, and has an important complementary role, by increasing the width of wood with high maturation strain. Without this factor, the efficiency of re-orientations would be reduced by 31% for angiosperms and 26% for gymnosperms. In the case of angiosperms, MOE is often larger in tension wood than in normal wood. Without these variations, the efficiency of re-orientations would be reduced by 13%. In the case of gymnosperm trees, MOE of compression wood is lower than that of normal wood, so that re-orientation efficiency would be increased by 24% without this factor of variations. 相似文献
10.
Sevush S 《Journal of theoretical biology》2006,238(3):704-725
By most accounts, the mind arises from the integrated activity of large populations of neurons distributed across multiple brain regions. A contrasting model is presented in the present paper that places the mind/brain interface not at the whole brain level but at the level of single neurons. Specifically, it is proposed that each neuron in the nervous system is independently conscious, with conscious content corresponding to the spatial pattern of a portion of that neuron's dendritic electrical activity. For most neurons, such as those in the hypothalamus or posterior sensory cortices, the conscious activity would be assumed to be simple and unable to directly affect the organism's macroscopic conscious behavior. For a subpopulation of layer 5 pyramidal neurons in the lateral prefrontal cortices, however, an arrangement is proposed to be present such that, at any given moment: (i) the spatial pattern of electrical activity in a portion of the dendritic tree of each neuron in the subpopulation individually manifests a complexity and diversity sufficient to account for the complexity and diversity of conscious experience; (ii) the dendritic trees of the neurons in the subpopulation all contain similar spatial electrical patterns; (iii) the spatial electrical pattern in the dendritic tree of each neuron interacts non-linearly with the remaining ambient dendritic electrical activity to determine the neuron's overall axonal response; (iv) the dendritic spatial pattern is reexpressed at the population level by the spatial pattern exhibited by a synchronously firing subgroup of the conscious neurons, thereby providing a mechanism by which conscious activity at the neuronal level can influence overall behavior. The resulting scheme is one in which conscious behavior appears to be the product of a single macroscopic mind, but is actually the integrated output of a chorus of minds, each associated with a different neuron. 相似文献
11.
A non-uniform equivalent cable model of membrane voltage changes in branching neuronal trees with active ion channels has
been developed. A general branching condition is formulated, extending Rall's 3/2 power rule for passive dendritic trees so
that non-uniform cable segments can be treated. The theoretical results support the use of the dendritic profile model of
Clements and Redman. The theory is then applied to dendrites of different morphological type yielding qualitative different
response behaviour.
Received: 25 September 1997 / Accepted: 13 November 1997 相似文献
12.
Dendritic morphology has an important influence on neuronal information processing. Multiple environmental cues, including neuronal activity, the neurotrophin family of growth factors, and extracellular guidance molecules have been shown to influence dendritic size, shape, and development. The Rho GTPases have emerged as key integrators of these environmental cues to regulate the underlying dendritic cytoskeleton. 相似文献
13.
Tortosa E Montenegro-Venegas C Benoist M Härtel S González-Billault C Esteban JA Avila J 《The Journal of biological chemistry》2011,286(47):40638-40648
Microtubule-associated protein 1B (MAP1B) is prominently expressed during early stages of neuronal development, and it has been implicated in axonal growth and guidance. MAP1B expression is also found in the adult brain in areas of significant synaptic plasticity. Here, we demonstrate that MAP1B is present in dendritic spines, and we describe a decrease in the density of mature dendritic spines in neurons of MAP1B-deficient mice that was accompanied by an increase in the number of immature filopodia-like protrusions. Although these neurons exhibited normal passive membrane properties and action potential firing, AMPA receptor-mediated synaptic currents were significantly diminished. Moreover, we observed a significant decrease in Rac1 activity and an increase in RhoA activity in the post-synaptic densities of adult MAP1B(+/-) mice when compared with wild type controls. MAP1B(+/-) fractions also exhibited a decrease in phosphorylated cofilin. Taken together, these results indicate a new and important role for MAP1B in the formation and maturation of dendritic spines, possibly through the regulation of the actin cytoskeleton. This activity of MAP1B could contribute to the regulation of synaptic activity and plasticity in the adult brain. 相似文献
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Dendritic morphology has been shown to have a dramatic impact on neuronal function. However, population features such as the inherent variability in dendritic morphology between cells belonging to the same neuronal type are often overlooked when studying computation in neural networks. While detailed models for morphology and electrophysiology exist for many types of single neurons, the role of detailed single cell morphology in the population has not been studied quantitatively or computationally. Here we use the structural context of the neural tissue in which dendritic trees exist to drive their generation in silico. We synthesize the entire population of dentate gyrus granule cells, the most numerous cell type in the hippocampus, by growing their dendritic trees within their characteristic dendritic fields bounded by the realistic structural context of (1) the granule cell layer that contains all somata and (2) the molecular layer that contains the dendritic forest. This process enables branching statistics to be linked to larger scale neuroanatomical features. We find large differences in dendritic total length and individual path length measures as a function of location in the dentate gyrus and of somatic depth in the granule cell layer. We also predict the number of unique granule cell dendrites invading a given volume in the molecular layer. This work enables the complete population-level study of morphological properties and provides a framework to develop complex and realistic neural network models. 相似文献
16.
Janet Alder Seth Kallman Alicia Palmieri Farah Khadim Jennifer J. Ayer Sujata Kumar Katherine Tsung Ilya Grinberg Smita Thakker‐Varia 《Developmental neurobiology》2013,73(10):769-784
Brain‐derived neurotrophic factor (BDNF) plays a facilitatory role in neuronal development and promotion of differentiation. Mechanisms that oppose BDNF's stimulatory effects create balance and regulate dendritic growth. However, these mechanisms have not been studied. We have focused our studies on the BDNF‐induced neuropeptide OrphaninFQ/ Nociceptin (OFQ); while BDNF is known to enhance synaptic activity, OFQ has opposite effects on activity, learning, and memory. We have now examined whether OFQ provides a balance to the stimulatory effects of BDNF on neuronal differentiation in the hippocampus. Golgi staining in OFQ knockout (KO) mice revealed an increase in primary dendrite length as well as spine density, suggesting that endogenous OFQ inhibits dendritic morphology. We have also used cultured hippocampal neurons to demonstrate that exogenous OFQ has an inhibitory effect on dendritic growth and that the neuropeptide alters the response to BDNF when pre‐administered. To determine if BDNF and OFQ act in a feedback loop, we inhibited the actions of the BDNF and OFQ receptors, TrkB and NOP using ANA‐12 and NOP KO mice respectively but our data suggest that the two factors do not act in a negative feedback loop. We found that the inhibition of dendritic morphology induced by OFQ is via enhanced RhoA activity. Finally, we have evidence that RhoA activation is required for the inhibitory effects of OFQ on dendritic morphology. Our results reveal basic mechanisms by which neurons not only regulate the formation of proper dendritic growth during development but also control plasticity in the mature nervous system. © 2013 Wiley Periodicals, Inc. Develop Neurobiol 73: 769–784, 2013 相似文献
17.
Chiou SH Shahi P Wagner RT Hu H Lapteva N Seethammagari M Sun SC Levitt JM Spencer DM 《EMBO reports》2011,12(9):971-979
The activation of innate and adaptive immunity is always balanced by inhibitory signalling mechanisms to maintain tissue integrity. We have identified the E3 ligase c-Cbl--known for its roles in regulating lymphocyte signalling--as a modulator of dendritic cell activation. In c-Cbl-deficient dendritic cells, Toll-like receptor-induced expression of proinflammatory factors, such as interleukin-12, is increased, correlating with a greater potency of dendritic-cell-based vaccines against established tumours. This proinflammatory phenotype is accompanied by an increase in nuclear factor (NF)-κB activity. In addition, c-Cbl deficiency reduces both p50 and p105 levels, which have been shown to modulate the stimulatory function of NF-κB. Our data indicate that c-Cbl has a crucial, RING-domain-dependent role in regulating dendritic cell maturation, probably by facilitating the regulatory function of p105 and/or p50. 相似文献
18.
Kwok-On Lai Zhuoyi Liang Erkang Fei Huiqian Huang Nancy Y. Ip 《The Journal of biological chemistry》2015,290(23):14637-14646
The maturation and maintenance of dendritic spines depends on neuronal activity and protein synthesis. One potential mechanism involves mammalian target of rapamycin, which promotes protein synthesis through phosphorylation of eIF4E-binding protein and p70 ribosomal S6 kinase 1 (S6K). Upon extracellular stimulation, mammalian target of rapamycin phosphorylates S6K at Thr-389. S6K also undergoes phosphorylation at other sites, including four serine residues in the autoinhibitory domain. Despite extensive biochemical studies, the importance of phosphorylation in the autoinhibitory domain in S6K function remains unresolved, and its role has not been explored in the cellular context. Here we demonstrated that S6K in neuron was phosphorylated at Ser-411 within the autoinhibitory domain by cyclin-dependent kinase 5. Ser-411 phosphorylation was regulated by neuronal activity and brain-derived neurotrophic factor (BDNF). Knockdown of S6K in hippocampal neurons by RNAi led to loss of dendritic spines, an effect that mimics neuronal activity blockade by tetrodotoxin. Notably, coexpression of wild type S6K, but not the phospho-deficient S411A mutant, could rescue the spine defects. These findings reveal the importance of cyclin-dependent kinase 5-mediated phosphorylation of S6K at Ser-411 in spine morphogenesis driven by BDNF and neuronal activity. 相似文献
19.
Arstikaitis P Gauthier-Campbell C Carolina Gutierrez Herrera R Huang K Levinson JN Murphy TH Kilimann MW Sala C Colicos MA El-Husseini A 《Molecular biology of the cell》2008,19(5):2026-2038
Dendritic filopodia are thought to participate in neuronal contact formation and development of dendritic spines; however, molecules that regulate filopodia extension and their maturation to spines remain largely unknown. Here we identify paralemmin-1 as a regulator of filopodia induction and spine maturation. Paralemmin-1 localizes to dendritic membranes, and its ability to induce filopodia and recruit synaptic elements to contact sites requires protein acylation. Effects of paralemmin-1 on synapse maturation are modulated by alternative splicing that regulates spine formation and recruitment of AMPA-type glutamate receptors. Paralemmin-1 enrichment at the plasma membrane is subject to rapid changes in neuronal excitability, and this process controls neuronal activity-driven effects on protrusion expansion. Knockdown of paralemmin-1 in developing neurons reduces the number of filopodia and spines formed and diminishes the effects of Shank1b on the transformation of existing filopodia into spines. Our study identifies a key role for paralemmin-1 in spine maturation through modulation of filopodia induction. 相似文献
20.
Saleh M. Al-Hussain 《Cellular and molecular neurobiology》1992,12(3):217-224
1. Golgi-Kopsch preparations of the oral ventral nuclei of human thalamus were analyzed in an attempt to classify the neuronal types. 2. Three types of neurons are described for the first time in humans. Type I neurons are large or medium in size and bear dendrites with protrusions, spines, and short hair-like appendages. Some have a radiate dendritic arbor and others have dendrites grouped in tufts. The dendritic trees of these neurons are dense. 3. Type II neurons are medium or small in size with less dense dendritic trees. These cells have somatic as well as dendritic appendages of different forms. 4. Relatively rare is a type of very small neurons, type III, with few and sparsely branching dendrites. 相似文献