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Revista de NeurologiaDendritic spines were first described by Ramón y Cajal in 1888, and considered by him to be the major sites of axo dendritic apposition and therefore of synaptic input... (Review)
Review
INTRODUCTION
Dendritic spines were first described by Ramón y Cajal in 1888, and considered by him to be the major sites of axo dendritic apposition and therefore of synaptic input in the CNS. Although a considerable wealth of information has been gathered over the last few decades about the function of spines in the mature nervous system, much less is known about how spines first appear on the otherwise smooth dendritic shafts.
DEVELOPMENT
The earliest dendritic appendages, known as filopodia, are long and thin protrusions that occur predominantly during early postnatal development of the mammalian CNS. It is tempting to consider filopodia simply as precursors to spines because at first glance their overall shape is similar to that of mature spines and because their expression during development precedes that of spines. However, the elongated shape of dendritic filopodia (reminiscent of that of axonal filopodia and filopodia in non-neuronal cells) suggests an exploratory function, so that their role may be to contact axons in order to establish early synapses, independently of the eventual formation of spines.
CONCLUSIONS
Here we review the literature on dendritic filopodia in an attempt to resolve this issue regarding these two distinct (though potentially overlapping) roles of filopodia in development: spinogenesis vs synaptogenesis. We summarize what is known about the physical characteristics and developmental time course of filopodia expression, as well as the mechanisms of growth and motility of these early dendritic protrusions, both in the intact nervous system and in pathologic settings. Throughout this review we present evidence that supports two hypotheses: that filopodia and spines are two inherently different types of protrusions, and that the role of dendritic filopodia is to capture axons and make early synapses, rather than transform into spines. Finally, we also discuss the potential role of filopodia in the sculpting of the dendritic tree. We also postulate that filopodia have additional important roles in regeneration and repair, in developmental plasticity and in the elaboration of dendritic arbors. These functions may not be limited to a specific developmental period, but probably extend into adulthood. We end by discussing specific experiments that could serve to test these hypotheses.
Topics: Animals; Dendrites; Models, Neurological; Nerve Regeneration; Neuronal Plasticity; Neurons; Pseudopodia; Synapses
PubMed: 11785056
DOI: No ID Found -
Developmental Neuroscience Aug 2010The hippocampus develops rapidly during the late fetal and early postnatal periods. Fetal/neonatal iron deficiency anemia (IDA) alters the genomic expression,...
The hippocampus develops rapidly during the late fetal and early postnatal periods. Fetal/neonatal iron deficiency anemia (IDA) alters the genomic expression, neurometabolism and electrophysiology of the hippocampus during the period of IDA and, strikingly, in adulthood despite neonatal iron treatment. To determine how early IDA affects the structural development of the apical dendrite arbor in hippocampal area CA1 in the offspring, pregnant rat dams were given an iron-deficient (ID) diet between gestational day 2 and postnatal day (P) 7 followed by rescue with an iron-sufficient (IS) diet. Apical dendrite morphology in hippocampus area CA1 was assessed at P15, P30 and P70 by Scholl analysis of Golgi-Cox-stained neurons. Messenger RNA levels of nine cytoplasmic and transmembrane proteins that are critical for dendrite growth were analyzed at P7, P15, P30 and P65 by quantitative real-time polymerase chain reaction. The ID group had reduced transcript levels of proteins that modify actin and tubulin dynamics [e.g. cofilin-1 (Cfl-1), profilin-1 (Pfn-1), and profilin-2 (Pfn-2)] at P7, followed at P15 by a proximal shift in peak branching, thinner third-generation dendritic branches and smaller-diameter spine heads. At P30, iron treatment since P7 resulted in recovery of all transcripts and structural components except for a continued proximal shift in peak branching. Nevertheless, at P65-P70, the formerly ID group showed a 32% reduction in 9 mRNA transcripts, including Cfl-1 and Pfn-1 and Pfn-2, accompanied by 25% fewer branches, that were also proximally shifted. These alterations may be due to early-life programming of genes important for structural plasticity during adulthood and may contribute to the abnormal long-term electrophysiology and recognition memory behavior that follows early iron deficiency.
Topics: Animals; Animals, Newborn; Cytoskeleton; Dendrites; Female; Hippocampus; Humans; Iron Deficiencies; Iron, Dietary; Pregnancy; Prenatal Exposure Delayed Effects; Rats; Rats, Sprague-Dawley
PubMed: 20689287
DOI: 10.1159/000314341 -
Physiology (Bethesda, Md.) Feb 2006Dendritic spines are small protrusions from neuronal dendrites that form the postsynaptic component of most excitatory synapses in the brain. They play critical roles in... (Review)
Review
Dendritic spines are small protrusions from neuronal dendrites that form the postsynaptic component of most excitatory synapses in the brain. They play critical roles in synaptic transmission and plasticity. Recent advances in imaging and molecular technologies reveal that spines are complex, dynamic structures that contain a dense array of cytoskeletal, transmembrane, and scaffolding molecules. Several neurological and psychiatric disorders exhibit dendritic spine abnormalities.
Topics: Animals; Cytoskeleton; Dendrites; Dendritic Spines; Humans; Nervous System Diseases; Neuronal Plasticity; Signal Transduction; Synapses; Synaptic Transmission; rho GTP-Binding Proteins
PubMed: 16443821
DOI: 10.1152/physiol.00042.2005 -
Neuron Dec 2016Most mammalian dendrites have surprisingly few copy numbers of mRNAs relative to the large number of synapses and consequently, at any given moment, the majority of... (Review)
Review
Most mammalian dendrites have surprisingly few copy numbers of mRNAs relative to the large number of synapses and consequently, at any given moment, the majority of synapses do not have a repertoire of mRNAs within their immediate locale capable of initiating translation-dependent plasticity. The dimensions of the translationally serviceable locale around synapses have boundary parameters that can be estimated. When a synapse receives an input beyond that boundary, the requisite mRNAs for local translation and plasticity may not be there. How a complex dendritic arbor optimizes this paucity of mRNAs opens several functional considerations that are related to the dynamic range of dendritic plasticity, sparse coding, and modifications of firing rates. RNA localization in dendrites may instantiate a neuron's history and establishes a bias toward inputs that synapse on RNA-laden synaptic clusters. Low copy numbers create an element of stochasticity to the induction of translation-dependent plasticity that allows the dendrite opportunities to respond to novel and unexpected inputs.
Topics: Dendrites; Humans; Neuronal Plasticity; Protein Biosynthesis; RNA Transport; RNA, Messenger; Synapses
PubMed: 28009273
DOI: 10.1016/j.neuron.2016.11.002 -
PLoS Computational Biology May 2019In order to record the stream of autobiographical information that defines our unique personal history, our brains must form durable memories from single brief exposures...
In order to record the stream of autobiographical information that defines our unique personal history, our brains must form durable memories from single brief exposures to the patterned stimuli that impinge on them continuously throughout life. However, little is known about the computational strategies or neural mechanisms that underlie the brain's ability to perform this type of "online" learning. Based on increasing evidence that dendrites act as both signaling and learning units in the brain, we developed an analytical model that relates online recognition memory capacity to roughly a dozen dendritic, network, pattern, and task-related parameters. We used the model to determine what dendrite size maximizes storage capacity under varying assumptions about pattern density and noise level. We show that over a several-fold range of both of these parameters, and over multiple orders-of-magnitude of memory size, capacity is maximized when dendrites contain a few hundred synapses-roughly the natural number found in memory-related areas of the brain. Thus, in comparison to entire neurons, dendrites increase storage capacity by providing a larger number of better-sized learning units. Our model provides the first normative theory that explains how dendrites increase the brain's capacity for online learning; predicts which combinations of parameter settings we should expect to find in the brain under normal operating conditions; leads to novel interpretations of an array of existing experimental results; and provides a tool for understanding which changes associated with neurological disorders, aging, or stress are most likely to produce memory deficits-knowledge that could eventually help in the design of improved clinical treatments for memory loss.
Topics: Animals; Brain; Computer Simulation; Dendrites; Humans; Learning; Memory; Models, Neurological; Neural Networks, Computer; Neuronal Plasticity; Neurons; Recognition, Psychology; Synapses
PubMed: 31050662
DOI: 10.1371/journal.pcbi.1006892 -
Nature Communications Aug 2018Highly motile dendritic protrusions are hallmarks of developing neurons. These exploratory filopodia sample the environment and initiate contacts with potential synaptic...
Highly motile dendritic protrusions are hallmarks of developing neurons. These exploratory filopodia sample the environment and initiate contacts with potential synaptic partners. To understand the role for dynamic filopodia in dendrite morphogenesis and experience-dependent structural plasticity, we analyzed dendrite dynamics, synapse formation, and dendrite volume expansion in developing ventral lateral neurons (LNvs) of the Drosophila larval visual circuit. Our findings reveal the temporal coordination between heightened dendrite dynamics with synaptogenesis in LNvs and illustrate the strong influence imposed by sensory experience on the prevalence of dendritic filopodia, which regulate the formation of synapses and the expansion of dendritic arbors. Using genetic analyses, we further identified Amphiphysin (Amph), a BAR (Bin/Amphiphysin/Rvs) domain-containing protein as a required component for tuning the dynamic state of LNv dendrites and promoting dendrite maturation. Taken together, our study establishes dynamic filopodia as the key cellular target for experience-dependent regulation of dendrite development.
Topics: Animals; Animals, Genetically Modified; Dendrites; Drosophila; Neurogenesis; Pseudopodia; Synapses; Ventral Thalamic Nuclei
PubMed: 30135566
DOI: 10.1038/s41467-018-05871-5 -
ENeuro 2020Precise information on synapse organization in a dendrite is crucial to understanding the mechanisms underlying voltage integration and the variability in the strength...
Precise information on synapse organization in a dendrite is crucial to understanding the mechanisms underlying voltage integration and the variability in the strength of synaptic inputs across dendrites of different complex morphologies. Here, we used focused ion beam/scanning electron microscope (FIB/SEM) to image the dendritic spines of mice in the hippocampal CA1 region, CA3 region, somatosensory cortex, striatum, and cerebellum (CB). Our results show that the spine geometry and dimensions differ across neuronal cell types. Despite this difference, dendritic spines were organized in an orchestrated manner such that the postsynaptic density (PSD) area per unit length of dendrite scaled positively with the dendritic diameter in CA1 proximal stratum radiatum (PSR), cortex, and CB. The ratio of the PSD area to neck length was kept relatively uniform across dendrites of different diameters in CA1 PSR. Computer simulation suggests that a similar level of synaptic strength across different dendrites in CA1 PSR enables the effective transfer of synaptic inputs from the dendrites toward soma. Excitatory postsynaptic potentials (EPSPs), evoked at single spines by glutamate uncaging and recorded at the soma, show that the neck length is more influential than head width in regulating the EPSP magnitude at the soma. Our study describes thorough morphologic features and the organizational principles of dendritic spines in different brain regions.
Topics: Animals; Computer Simulation; Dendrites; Excitatory Postsynaptic Potentials; Mice; Neurons; Synapses
PubMed: 33109633
DOI: 10.1523/ENEURO.0248-20.2020 -
Proceedings of the National Academy of... Jun 2001The functioning of the neuronal dendrite results from a variety of biological processes including mRNA transport to and protein translation in the dendrite. The... (Review)
Review
The functioning of the neuronal dendrite results from a variety of biological processes including mRNA transport to and protein translation in the dendrite. The complexity of the mRNA population in dendrites suggests that specific biological processes are modulated through the regulation of dendritic biology. There are various classes of mRNAs in dendrites whose translation modulates the ability of the dendrite to receive and integrate presynaptic information. Among these mRNAs are those encoding selective transcription factors that function in the neuronal soma and ionotropic glutamate receptors that function on the neuronal membrane. Conclusive evidence that these mRNAs can be translated is reviewed, and identification of the endogenous sites of translation in living dendrites is presented. These data, as well as those described in the other articles resulting from this colloquium, highlight the complexity of dendritic molecular biology and the exquisitely selective and sensitive modulatory role played by the dendrite in facilitating intracellular and intercellular communication.
Topics: Animals; Cell Membrane; Dendrites; Neurons; Protein Biosynthesis; RNA, Messenger; Receptors, Glutamate; Ribosomes; Second Messenger Systems
PubMed: 11416191
DOI: 10.1073/pnas.121146698 -
ELife Nov 2020Class I ventral posterior dendritic arborisation (c1vpda) proprioceptive sensory neurons respond to contractions in the larval body wall during crawling. Their...
Class I ventral posterior dendritic arborisation (c1vpda) proprioceptive sensory neurons respond to contractions in the larval body wall during crawling. Their dendritic branches run along the direction of contraction, possibly a functional requirement to maximise membrane curvature during crawling contractions. Although the molecular machinery of dendritic patterning in c1vpda has been extensively studied, the process leading to the precise elaboration of their comb-like shapes remains elusive. Here, to link dendrite shape with its proprioceptive role, we performed long-term, non-invasive, in vivo time-lapse imaging of c1vpda embryonic and larval morphogenesis to reveal a sequence of differentiation stages. We combined computer models and dendritic branch dynamics tracking to propose that distinct sequential phases of stochastic growth and retraction achieve efficient dendritic trees both in terms of wire and function. Our study shows how dendrite growth balances structure-function requirements, shedding new light on general principles of self-organisation in functionally specialised dendrites.
Topics: Animals; Animals, Genetically Modified; Dendrites; Drosophila; Drosophila Proteins; Gene Expression Regulation, Developmental; Green Fluorescent Proteins; Morphogenesis; Sensory Receptor Cells
PubMed: 33241995
DOI: 10.7554/eLife.60920 -
Experimental Neurology Nov 2020We investigated the ability of agmatine to potentiate the antidepressant-like and synaptic effects of ketamine in mice. Agmatine (0.1 and 1 mg/kg, p.o.) and ketamine (1...
We investigated the ability of agmatine to potentiate the antidepressant-like and synaptic effects of ketamine in mice. Agmatine (0.1 and 1 mg/kg, p.o.) and ketamine (1 and 10 mg/kg, i.p.) produced an antidepressant-like effect in the tail suspension test. The combination of agmatine (0.01 mg/kg, p.o.) and ketamine (0.1 mg/kg, i.p.), at subthreshold doses, produced an antidepressant-like effect 1 h, 24 h and 7d after treatment. Western blot analysis from prefrontal cortex tissue showed that the combined treatment, after 1 h, increased p70S6K and GluA1, and reduced synapsin 1 phosphorylation. Additionally, after 24 h, Akt, p70S6K, GluA1, and synapsin 1 phosphorylation; and PSD95 immunocontent increased (which persisted for up to 7d). Dendritic architecture analysis of the prefrontal cortex revealed that the combined treatment improved dendritic arbor complexity (after 24 h, up to 7d), and increased spine density (after 1 h, up to 24 h). Morphometric analysis revealed a filopodia-shaped dendrite spine upregulation after 1 h. A predominance of stubby, mushroom, branched and filopodia; and a reduction in thin protrusions were observed after 24 h. Finally, mushroom-shaped dendritic spines predominance increased after 7d. Agmatine potentiated ketamine's antidepressant, and dendritic arbors and spines remodeling effects in a time-dependent manner. Our data indicate Akt/p70S6K signaling as a likely target for these effects.
Topics: Agmatine; Animals; Antidepressive Agents; Dendrites; Dendritic Spines; Drug Synergism; Hindlimb Suspension; Ketamine; Male; Mice; Motor Activity; Oncogene Protein v-akt; Prefrontal Cortex; Ribosomal Protein S6 Kinases; Signal Transduction; Synapses
PubMed: 32659382
DOI: 10.1016/j.expneurol.2020.113398