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Journal of Neurochemistry Jul 2007The dendritic arbor is responsible for receiving and consolidating neuronal input. Outgrowth and morphogenesis of the arbor are complex stages of development that are... (Review)
Review
The dendritic arbor is responsible for receiving and consolidating neuronal input. Outgrowth and morphogenesis of the arbor are complex stages of development that are poorly understood. However, recent findings have identified synaptic scaffolding proteins as novel regulators of these important events. Scaffolding proteins are enriched in the post-synaptic density where they bind and bring into close proximity neurotransmitter receptors, signaling molecules, and regulators of the actin cytoskeleton. This property is important for dendritic spine morphogenesis and maintenance in the mature neuron. Scaffolding proteins are now being described as key regulators of neurite outgrowth, dendritic development, and pattern formation in immature neurons. These proteins, which include post-synaptic-95, Shank and Densin-180, as well as many of their interacting partners, appear to regulate both the microtubule and actin cytoskeleton to influence dendrite morphology. Through a large array of protein-protein interaction domains, scaffolding proteins are able to form large macromolecular complexes that include cytoskeletal motor proteins as well as microtubule and actin regulatory molecules. Together, the new findings form a persuasive argument that scaffolding proteins deliver critical regulatory elements to sites of dendritic outgrowth and branching to modulate the formation and maintenance of the dendritic arbor.
Topics: Animals; Cell Differentiation; Cell Shape; Central Nervous System; Cytoskeleton; Dendrites; Disks Large Homolog 4 Protein; Humans; Intracellular Signaling Peptides and Proteins; Membrane Proteins; Molecular Motor Proteins; Synaptic Membranes
PubMed: 17596209
DOI: 10.1111/j.1471-4159.2007.04662.x -
Scientific Reports Apr 2022Synaptic plasticity is a long-lasting core hypothesis of brain learning that suggests local adaptation between two connecting neurons and forms the foundation of machine...
Synaptic plasticity is a long-lasting core hypothesis of brain learning that suggests local adaptation between two connecting neurons and forms the foundation of machine learning. The main complexity of synaptic plasticity is that synapses and dendrites connect neurons in series and existing experiments cannot pinpoint the significant imprinted adaptation location. We showed efficient backpropagation and Hebbian learning on dendritic trees, inspired by experimental-based evidence, for sub-dendritic adaptation and its nonlinear amplification. It has proven to achieve success rates approaching unity for handwritten digits recognition, indicating realization of deep learning even by a single dendrite or neuron. Additionally, dendritic amplification practically generates an exponential number of input crosses, higher-order interactions, with the number of inputs, which enhance success rates. However, direct implementation of a large number of the cross weights and their exhaustive manipulation independently is beyond existing and anticipated computational power. Hence, a new type of nonlinear adaptive dendritic hardware for imitating dendritic learning and estimating the computational capability of the brain must be built.
Topics: Dendrites; Machine Learning; Neuronal Plasticity; Neurons; Synapses
PubMed: 35484180
DOI: 10.1038/s41598-022-10466-8 -
PLoS Computational Biology Apr 2022Dendritic spines are highly dynamic neuronal compartments that control the synaptic transmission between neurons. Spines form ultrastructural units, coupling synaptic...
Dendritic spines are highly dynamic neuronal compartments that control the synaptic transmission between neurons. Spines form ultrastructural units, coupling synaptic contact sites to the dendritic shaft and often harbor a spine apparatus organelle, composed of smooth endoplasmic reticulum, which is responsible for calcium sequestration and release into the spine head and neck. The spine apparatus has recently been linked to synaptic plasticity in adult human cortical neurons. While the morphological heterogeneity of spines and their intracellular organization has been extensively demonstrated in animal models, the influence of spine apparatus organelles on critical signaling pathways, such as calcium-mediated dynamics, is less well known in human dendritic spines. In this study we used serial transmission electron microscopy to anatomically reconstruct nine human cortical spines in detail as a basis for modeling and simulation of the calcium dynamics between spine and dendrite. The anatomical study of reconstructed human dendritic spines revealed that the size of the postsynaptic density correlates with spine head volume and that the spine apparatus volume is proportional to the spine volume. Using a newly developed simulation pipeline, we have linked these findings to spine-to-dendrite calcium communication. While the absence of a spine apparatus, or the presence of a purely passive spine apparatus did not enable any of the reconstructed spines to relay a calcium signal to the dendritic shaft, the calcium-induced calcium release from this intracellular organelle allowed for finely tuned "all-or-nothing" spine-to-dendrite calcium coupling; controlled by spine morphology, neck plasticity, and ryanodine receptors. Our results suggest that spine apparatus organelles are strategically positioned in the neck of human dendritic spines and demonstrate their potential relevance to the maintenance and regulation of spine-to-dendrite calcium communication.
Topics: Animals; Calcium; Dendrites; Dendritic Spines; Humans; Neuronal Plasticity; Neurons; Synapses; Synaptic Transmission
PubMed: 35468131
DOI: 10.1371/journal.pcbi.1010069 -
Biochimica Et Biophysica Acta Feb 2008Polarized growth of the neuron would logically require some form of membrane traffic to the tip of the growth cone, regulated in conjunction with other trafficking... (Review)
Review
Polarized growth of the neuron would logically require some form of membrane traffic to the tip of the growth cone, regulated in conjunction with other trafficking processes that are common to both neuronal and non-neuronal cells. Unlike axons, dendrites are endowed with membranous organelles of the exocytic pathway extending from the cell soma, including both rough and smooth endoplasmic reticulum (ER) and the ER-Golgi intermediate compartment (ERGIC). Dendrites also have satellite Golgi-like cisternal stacks known as Golgi outposts that have no membranous connections with the somatic Golgi. Golgi outposts presumably serve both general and specific local trafficking needs, and could mediate membrane traffic required for polarized dendritic growth during neuronal differentiation. Recent findings suggest that dendritic growth, but apparently not axonal growth, relies very much on classical exocytic traffic, and is affected by defects in components of both the early and late secretory pathways. Within dendrites, localized processes of recycling endosome-based exocytosis regulate the growth of dendritic spines and postsynaptic compartments. Emerging membrane traffic processes and components that contribute specifically to dendritic growth are discussed.
Topics: Animals; Biological Transport; Dendrites; Exocytosis; Humans; Intracellular Membranes; trans-Golgi Network
PubMed: 18155172
DOI: 10.1016/j.bbamcr.2007.11.011 -
Progress in Biophysics and Molecular... May 2004Maxwell's equations are taken as the starting point for the development of a mathematical model of a dendrite. The three-dimensional model of the evolution of the... (Review)
Review
Maxwell's equations are taken as the starting point for the development of a mathematical model of a dendrite. The three-dimensional model of the evolution of the dendritic membrane potential based on these equations gives rise to a hierarchy of one-dimensional membrane equations. Under sufficiently strong assumptions, the first membrane equation is identical to the conventional cable equation. The second membrane equation explicitly includes the influence of dendritic taper and non-axial gradients in the intra-cellular potential. The procedure of starting from a three-dimensional model and extracting from it a one-dimensional approximation provides a prescription of how to incorporate three-dimensional properties of a dendrite in a one-dimensional representation, by contrast with an approach which aims to modify the traditional cable equation to take account of three-dimensional structure. Finite element methods are used to solve the membrane equations. An example based on a simple model of a tapered dendrite with differently placed distributions of synaptic input suggests that the effect of taper on the spike train output from the model is more important for distal synapses than those closer to the soma.
Topics: Animals; Cell Membrane; Dendrites; Electric Conductivity; Electromagnetic Fields; Electrophysiology; Mathematics; Membrane Potentials; Models, Theoretical; Neurons
PubMed: 15050381
DOI: 10.1016/j.pbiomolbio.2003.08.001 -
Developmental Cell Jan 2019The mechanisms that pattern and maintain dendritic arbors are key to understanding the principles that govern nervous system assembly. The activity of presynaptic axons...
The mechanisms that pattern and maintain dendritic arbors are key to understanding the principles that govern nervous system assembly. The activity of presynaptic axons has long been known to shape dendrites, but activity-independent functions of axons in this process have remained elusive. Here, we show that in Caenorhabditis elegans, the axons of the ALA neuron control guidance and extension of the 1° dendrites of PVD somatosensory neurons independently of ALA activity. PVD 1° dendrites mimic ALA axon guidance defects in loss-of-function mutants for the extracellular matrix molecule MIG-6/Papilin or the UNC-6/Netrin pathway, suggesting that axon-dendrite adhesion is important for dendrite formation. We found that the SAX-7/L1CAM cell adhesion molecule engages in distinct molecular mechanisms to mediate extensions of PVD 1° dendrites and maintain the ALA-PVD axon-dendritic fascicle, respectively. Thus, axons can serve as critical scaffolds to pattern and maintain dendrites through contact-dependent but activity-independent mechanisms.
Topics: Animals; Axons; Caenorhabditis elegans; Caenorhabditis elegans Proteins; Cell Adhesion Molecules; Dendrites; Nerve Tissue Proteins; Neuronal Plasticity; Neurons
PubMed: 30661986
DOI: 10.1016/j.devcel.2018.12.015 -
The Journal of Neuroscience : the... Jul 2013Memory deficits in Drosophila nalyot mutants suggest that the Myb family transcription factor Adf-1 is an important regulator of developmental plasticity in the brain....
Memory deficits in Drosophila nalyot mutants suggest that the Myb family transcription factor Adf-1 is an important regulator of developmental plasticity in the brain. However, the cellular functions for this transcription factor in neurons or molecular mechanisms by which it regulates plasticity remain unknown. Here, we use in vivo 3D reconstruction of identifiable larval motor neuron dendrites to show that Adf-1 is required cell autonomously for dendritic development and activity-dependent plasticity of motor neurons downstream of CaMKII. Adf-1 inhibition reduces dendrite growth and neuronal excitability, and results in motor deficits and altered transcriptional profiles. Surprisingly, analysis by comparative chromatin immunoprecipitation followed by sequencing (ChIP-Seq) of Adf-1, RNA Polymerase II (Pol II), and histone modifications in Kc cells shows that Adf-1 binding correlates positively with high Pol II-pausing indices and negatively with active chromatin marks such as H3K4me3 and H3K27ac. Consistently, the expression of Adf-1 targets Staufen and Fasciclin II (FasII), identified through larval brain ChIP-Seq for Adf-1, is negatively regulated by Adf-1, and manipulations of these genes predictably modify dendrite growth. Our results imply mechanistic interactions between transcriptional and local translational machinery in neurons as well as conserved neuronal growth mechanisms mediated by cell adhesion molecules, and suggest that CaMKII, Adf-1, FasII, and Staufen influence crucial aspects of dendrite development and plasticity with potential implications for memory formation. Further, our experiments reveal molecular details underlying transcriptional regulation by Adf-1, and indicate active interaction between Adf-1 and epigenetic regulators of gene expression during activity-dependent neuronal plasticity.
Topics: Animals; Behavior, Animal; Calcium-Calmodulin-Dependent Protein Kinase Type 2; Cell Adhesion Molecules, Neuronal; Dendrites; Drosophila; Drosophila Proteins; Gene Expression Regulation, Developmental; Larva; Neuronal Plasticity; Neurons; RNA-Binding Proteins; Transcription Factors
PubMed: 23864680
DOI: 10.1523/JNEUROSCI.1760-13.2013 -
Nature Neuroscience Feb 2011Axons navigating through the developing nervous system are instructed by external attractive and repulsive cues. Emerging evidence suggests the same cues control...
Axons navigating through the developing nervous system are instructed by external attractive and repulsive cues. Emerging evidence suggests the same cues control dendrite development, but it is not understood how they differentially instruct axons and dendrites. We studied a C. elegans motor neuron whose axon and dendrite adopt different trajectories and lengths. We found that the guidance cue UNC-6 (Netrin) is required for both axon and dendrite development. Its repulsive receptor UNC-5 repelled the axon from the ventral cell body, whereas the attractive receptor UNC-40 (DCC) was dendritically enriched and promotes antero-posterior dendritic growth. Although the endogenous ventrally secreted UNC-6 instructs axon guidance, dorsal or even membrane-tethered UNC-6 could support dendrite development. Unexpectedly, the serine-threonine kinase PAR-4 (LKB1) was selectively required for the activity of the UNC-40 pathway in dendrite outgrowth. These data suggest that axon and dendrite of one neuron interpret common environmental cues with different receptors and downstream signaling pathways.
Topics: Animals; Animals, Genetically Modified; Caenorhabditis elegans; Caenorhabditis elegans Proteins; Cell Adhesion Molecules; Cell Movement; Dendrites; Nerve Tissue Proteins; Netrins; Neurons; Protein Serine-Threonine Kinases; Receptors, Cell Surface; Signal Transduction
PubMed: 21186357
DOI: 10.1038/nn.2717 -
Proceedings of the National Academy of... Aug 2021Dendrites play an essential role in the integration of highly fluctuating input in vivo into neurons across all nervous systems. Yet, they are often studied under...
Dendrites play an essential role in the integration of highly fluctuating input in vivo into neurons across all nervous systems. Yet, they are often studied under conditions where inputs to dendrites are sparse. The dynamic properties of active dendrites facing in vivo-like fluctuating input thus remain elusive. In this paper, we uncover dynamics in a canonical model of a dendritic compartment with active calcium channels, receiving in vivo-like fluctuating input. In a single-compartment model of the active dendrite with fast calcium activation, we show noise-induced nonmonotonic behavior in the relationship of the membrane potential output, and mean input emerges. In contrast, noise can induce bistability in the input-output relation in the system with slowly activating calcium channels. Both phenomena are absent in a noiseless condition. Furthermore, we show that timescales of the emerging stochastic bistable dynamics extend far beyond a deterministic system due to stochastic switching between the solutions. A numerical simulation of a multicompartment model neuron shows that in the presence of in vivo-like synaptic input, the bistability uncovered in our analysis persists. Our results reveal that realistic synaptic input contributes to sustained dendritic nonlinearities, and synaptic noise is a significant component of dendritic input integration.
Topics: Action Potentials; Calcium Channels; Cell Membrane; Computer Simulation; Dendrites; Models, Neurological; Stochastic Processes; Synapses; Time Factors
PubMed: 34413187
DOI: 10.1073/pnas.2023381118 -
Scientific Reports Jul 2016GluA2-containing AMPA receptors (AMPARs) play a critical role in various aspects of neurodevelopment. However, the molecular mechanisms underlying these processes are...
GluA2-containing AMPA receptors (AMPARs) play a critical role in various aspects of neurodevelopment. However, the molecular mechanisms underlying these processes are largely unknown. We report here that the interaction between GluA2 and glyceraldehyde 3-phosphate dehydrogenase (GAPDH) is necessary for neuron and cortical development. Using an interfering peptide (GluA2-G-Gpep) that specifically disrupts this interaction, we found that primary neuron cultures with peptide treatment displayed growth cone development deficits, impairment of axon formation, less dendritic arborization and lower spine protrusion density. Consistently, in vivo data with mouse brains from pregnant dams injected with GluA2-G-Gpep daily during embryonic day 8 to 19 revealed a reduction of cortical tract axon integrity and neuronal density in post-natal day 1 offspring. Disruption of GluA2-GAPDH interaction also impairs the GluA2-Plexin A4 interaction and reduces p53 acetylation in mice, both of which are possible mechanisms leading to the observed neurodevelopmental abnormalities. Furthermore, electrophysiological experiments indicate altered long-term potentiation (LTP) in hippocampal slices of offspring mice. Our results provide novel evidence that AMPARs, specifically the GluA2 subunit via its interaction with GAPDH, play a critical role in cortical neurodevelopment.
Topics: Acetylation; Amino Acid Sequence; Animals; Animals, Newborn; Axons; Brain; Calcium Channels; Cell Count; Cell Proliferation; Cells, Cultured; Dendrites; Dendritic Spines; Embryo, Mammalian; Glyceraldehyde-3-Phosphate Dehydrogenases; Growth Cones; Lysine; Mice; Nerve Tissue Proteins; Neurogenesis; Peptide Fragments; Peptides; Receptors, AMPA; Receptors, Cell Surface; Synapses
PubMed: 27461448
DOI: 10.1038/srep30458