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Scientific Reports Jan 2015Memory is fixed solidly by repetition. However, the cellular mechanism underlying this repetition-dependent memory consolidation/reconsolidation remains unclear. In our...
Memory is fixed solidly by repetition. However, the cellular mechanism underlying this repetition-dependent memory consolidation/reconsolidation remains unclear. In our previous study using stable slice cultures of the rodent hippocampus, we found long-lasting synaptic enhancement/suppression coupled with synapse formation/elimination after repeated inductions of chemical LTP/LTD, respectively. We proposed these phenomena as useful model systems for analyzing repetition-dependent memory consolidation. Recently, we analyzed the dynamics of dendritic spines during development of the enhancement, and found that the spines increased in number following characteristic stochastic processes. The current study investigates spine dynamics during the development of the suppression. We found that the rate of spine retraction increased immediately leaving that of spine generation unaltered. Spine elimination occurred independent of the pre-existing spine density on the dendritic segment. In terms of elimination, mushroom-type spines were not necessarily more stable than stubby-type and thin-type spines.
Topics: Animals; Dendritic Spines; Fluorescent Dyes; Hippocampus; In Vitro Techniques; Long-Term Potentiation; Methoxyhydroxyphenylglycol; Mice; Mice, Transgenic; Microscopy, Confocal; Synapses; Time Factors
PubMed: 25573377
DOI: 10.1038/srep07707 -
Developmental Neurobiology Jul 2021Dendritic spines are membranous protrusions that receive essentially all excitatory inputs in most mammalian neurons. Spines, with a bulbous head connected to the...
Dendritic spines are membranous protrusions that receive essentially all excitatory inputs in most mammalian neurons. Spines, with a bulbous head connected to the dendrite by a thin neck, have a variety of morphologies that likely impact their functional properties. Nevertheless, the question of whether spines belong to distinct morphological subtypes is still open. Addressing this quantitatively requires clear identification and measurements of spine necks. Recent advances in electron microscopy enable large-scale systematic reconstructions of spines with nanometer precision in 3D. Analyzing ultrastructural reconstructions from mouse neocortical neurons with computer vision algorithms, we demonstrate that the vast majority of spine structures can be rigorously separated into heads and necks, enabling morphological measurements of spine necks. We then used a database of spine morphological parameters to explore the potential existence of different spine classes. Without exception, our analysis revealed unimodal distributions of individual morphological parameters of spine heads and necks, without evidence for subtypes of spines. The postsynaptic density size was strongly correlated with the spine head volume. The spine neck diameter, but not the neck length, was also correlated with the head volume. Spines with larger head volumes often had a spine apparatus and pairs of spines in a post-synaptic cell contacted by the same axon had similar head volumes. Our data reveal a lack of morphological subtypes of spines and indicate that the spine neck length and head volume must be independently regulated. These results have repercussions for our understanding of the function of dendritic spines in neuronal circuits.
Topics: Animals; Axons; Dendrites; Dendritic Spines; Mammals; Mice; Microscopy, Electron; Neurons; Synapses
PubMed: 33977655
DOI: 10.1002/dneu.22829 -
Neuron Sep 2017Since Cajal's first drawings of Golgi stained neurons, generations of researchers have been fascinated by the small protrusions, termed spines, studding many neuronal... (Review)
Review
Since Cajal's first drawings of Golgi stained neurons, generations of researchers have been fascinated by the small protrusions, termed spines, studding many neuronal dendrites. Most excitatory synapses in the mammalian CNS are located on dendritic spines, making spines convenient proxies for excitatory synaptic presence. When in vivo imaging revealed that dendritic spines are dynamic structures, their addition and elimination were interpreted as excitatory synapse gain and loss, respectively. Spine imaging has since become a popular assay for excitatory circuit remodeling. In this review, we re-evaluate the validity of using spine dynamics as a straightforward reflection of circuit rewiring. Recent studies tracking both spines and synaptic markers in vivo reveal that 20% of spines lack PSD-95 and are short lived. Although they account for most spine dynamics, their remodeling is unlikely to impact long-term network structure. We discuss distinct roles that spine dynamics can play in circuit remodeling depending on synaptic content.
Topics: Animals; Dendritic Spines; Nerve Tissue Proteins; Synapses
PubMed: 28957675
DOI: 10.1016/j.neuron.2017.08.008 -
Cells Jul 2021Neurogenesis and functional brain activity require complex associations of inherently programmed secretory elements that are regulated precisely and temporally. Family...
Neurogenesis and functional brain activity require complex associations of inherently programmed secretory elements that are regulated precisely and temporally. Family with sequence similarity 19 A1 (FAM19A1) is a secreted protein primarily expressed in subsets of terminally differentiated neuronal precursor cells and fully mature neurons in specific brain substructures. Several recent studies have demonstrated the importance of FAM19A1 in brain physiology; however, additional information is needed to support its role in neuronal maturation and function. In this study, dendritic spine morphology in -ablated mice and neurite development during in vitro neurogenesis were examined to understand the putative role of FAM19A1 in neural integrity. Adult -deficient mice showed low dendritic spine density and maturity with reduced dendrite complexity compared to wild-type (WT) littermates. To further explore the effect of FAM19A1 on neuronal maturation, the neurite outgrowth pattern in primary neurons was analyzed in vitro with and without FAM19A1. In response to FAM19A1, WT primary neurons showed reduced neurite complexity, whereas -decifient primary neurons exhibited increased neurite arborization, which was reversed by supplementation with recombinant FAM19A1. Together, these findings suggest that FAM19A1 participates in dendritic spine development and neurite arborization.
Topics: Age Factors; Animals; Brain; Cells, Cultured; Chemokines; Dendritic Spines; Female; Gestational Age; Male; Mice, Inbred C57BL; Mice, Knockout; Neurites; Neuronal Outgrowth; Pregnancy; Signal Transduction; Mice
PubMed: 34440636
DOI: 10.3390/cells10081868 -
ELife Apr 2022Dendritic spines are the central postsynaptic machinery that determines synaptic function. The F-actin within dendritic spines regulates their dynamic formation and...
Dendritic spines are the central postsynaptic machinery that determines synaptic function. The F-actin within dendritic spines regulates their dynamic formation and elimination. Rai14 is an F-actin-regulating protein with a membrane-shaping function. Here, we identified the roles of Rai14 for the regulation of dendritic spine dynamics associated with stress-induced depressive-like behaviors. Rai14-deficient neurons exhibit reduced dendritic spine density in the mouse brain, resulting in impaired functional synaptic activity. Rai14 was protected from degradation by complex formation with Tara, and accumulated in the dendritic spine neck, thereby enhancing spine maintenance. Concurrently, Rai14 deficiency in mice altered gene expression profile relevant to depressive conditions and increased depressive-like behaviors. Moreover, Rai14 expression was reduced in the prefrontal cortex of the mouse stress model, which was blocked by antidepressant treatment. Thus, we propose that Rai14-dependent regulation of dendritic spines may underlie the plastic changes of neuronal connections relevant to depressive-like behaviors.
Topics: Actin Cytoskeleton; Actins; Animals; Dendritic Spines; Disease Models, Animal; Mice; Neurons; Tretinoin
PubMed: 35467532
DOI: 10.7554/eLife.77755 -
Journal of Neuroscience Methods Mar 2017Neuronal morphology and function are highly coupled. In particular, dendritic spine morphology is strongly governed by the incoming neuronal activity. The first step...
BACKGROUND
Neuronal morphology and function are highly coupled. In particular, dendritic spine morphology is strongly governed by the incoming neuronal activity. The first step towards understanding the structure-function relationships is to classify spine shapes into the main spine types suggested in the literature. Due to the lack of reliable automated analysis tools, classification is mostly performed manually, which is a time-intensive task and prone to subjectivity.
NEW METHOD
We propose an automated method to classify dendritic spines using shape and appearance features based on challenging two-photon laser scanning microscopy (2PLSM) data. Disjunctive Normal Shape Models (DNSM) is a recently proposed parametric shape representation. We perform segmentation of spine images by applying DNSM and use the resulting representation as shape features. Furthermore, we use Histogram of oriented gradients (HOG) to extract appearance features. In this context, we propose a kernel density estimation (KDE) based framework for dendritic spine classification, which uses these shape and appearance features.
RESULTS
Our shape and appearance features based approach combined with Neural Network (NN) correctly classifies 87.06% of spines on a dataset of 456 spines.
COMPARISON WITH EXISTING METHODS
Our proposed method outperforms standard morphological feature based approaches. Our KDE based framework also enables neuroscientists to analyze the separability of spine shape classes in the likelihood ratio space, which leads to further insights about nature of the spine shape analysis problem.
CONCLUSIONS
Results validate that performance of our proposed approach is comparable to a human expert. It also enable neuroscientists to study shape statistics in the likelihood ratio space.
Topics: Animals; Data Interpretation, Statistical; Dendritic Spines; Hippocampus; Imaging, Three-Dimensional; Machine Learning; Mice; Microscopy, Confocal; Pattern Recognition, Automated; Tissue Culture Techniques
PubMed: 27998713
DOI: 10.1016/j.jneumeth.2016.12.006 -
The EMBO Journal Dec 2014Spines are highly motile protrusions emerging from the dendritic shafts of neurons. The dynamics of these post-synaptic structures are ruled by actin filament turnover....
Spines are highly motile protrusions emerging from the dendritic shafts of neurons. The dynamics of these post-synaptic structures are ruled by actin filament turnover. However, our understanding of the mechanisms of actin polymerization in dendritic spines is quite ambiguous. A recent study by the Giannone laboratory (Chazeau , 2014) is now shedding some light on the peculiar features of actin polymerization in dendritic spines, which are distinct from the known canonical mechanisms.
Topics: Actin-Related Protein 2-3 Complex; Actins; Animals; Dendritic Spines; Models, Biological; Post-Synaptic Density; Synaptic Transmission
PubMed: 25326188
DOI: 10.15252/embj.201490137 -
Experimental Neurology May 2012Spinal cord injury (SCI) often results in the development of neuropathic pain, which can persist for months and years after injury. Although many aberrant changes to... (Review)
Review
Spinal cord injury (SCI) often results in the development of neuropathic pain, which can persist for months and years after injury. Although many aberrant changes to sensory processing contribute to the development of chronic pain, emerging evidence demonstrates that mechanisms similar to those underlying classical learning and memory can contribute to central sensitization, a phenomenon of amplified responsiveness to stimuli in nociceptive dorsal horn neurons. Notably, dendritic spines have emerged as major players in learning and memory, providing a structural substrate for how the nervous system modifies connections to form and store information. Until now, most information regarding dendritic spines has been obtained from studies in the brain. Recent experimental data in the spinal cord, however, demonstrate that Rac1-regulated dendritic spine remodeling occurs on second-order wide dynamic range neurons and accompanies neuropathic pain after SCI. Thus, SCI-induced synaptic potentiation engages a putative spinal memory mechanism. A compelling, novel possibility for pain research is that a synaptic model of long-term memory storage could explain the persistent nature of neuropathic pain. Such a conceptual bridge between pain and memory could guide the development of more effective strategies for treatment of chronic pain after injury to the nervous system.
Topics: Animals; Dendritic Spines; Memory; Neuralgia; Neuronal Plasticity; Neurons; Spinal Cord Injuries; Synapses
PubMed: 21925174
DOI: 10.1016/j.expneurol.2011.08.026 -
Cells Feb 2020The protein kinase JNK1 exhibits high activity in the developing brain, where it regulates dendrite morphology through the phosphorylation of cytoskeletal regulatory...
The protein kinase JNK1 exhibits high activity in the developing brain, where it regulates dendrite morphology through the phosphorylation of cytoskeletal regulatory proteins. JNK1 also phosphorylates dendritic spine proteins, and mice display a long-term depression deficit. Whether JNK1 or other JNKs regulate spine morphology is thus of interest. Here, we characterize dendritic spine morphology in hippocampus of mice lacking using Lucifer yellow labelling. We find that mushroom spines decrease and thin spines increase in apical dendrites of CA3 pyramidal neurons with no spine changes in basal dendrites or in CA1. Consistent with this spine deficit, mice display impaired acquisition learning in the Morris water maze. In hippocampal cultures, we show that cytosolic but not nuclear JNK, regulates spine morphology and expression of phosphomimicry variants of JNK substrates doublecortin (DCX) or myristoylated alanine-rich C kinase substrate-like protein-1 (MARCKSL1), rescue mushroom, thin, and stubby spines differentially. These data suggest that physiologically active JNK controls the equilibrium between mushroom, thin, and stubby spines via phosphorylation of distinct substrates.
Topics: Animals; Dendritic Spines; Doublecortin Protein; Humans; MAP Kinase Kinase 4; MAP Kinase Signaling System; Mice; Morris Water Maze Test; Transfection
PubMed: 32074971
DOI: 10.3390/cells9020440 -
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