Do Thin Spines Learn to Be Mushroom Spines That Remember? Jennifer Bourne and Kristen M Harris
Total Page:16
File Type:pdf, Size:1020Kb
Load more
Recommended publications
-
Cooperative Astrocyte and Dendritic Spine Dynamics at Hippocampal Excitatory Synapses
The Journal of Neuroscience, August 30, 2006 • 26(35):8881–8891 • 8881 Development/Plasticity/Repair Cooperative Astrocyte and Dendritic Spine Dynamics at Hippocampal Excitatory Synapses Michael Haber, Lei Zhou, and Keith K. Murai Centre for Research in Neuroscience, Department of Neurology and Neurosurgery, The Research Institute of the McGill University Health Centre, Montreal General Hospital, Montreal, Quebec, H3G 1A4, Canada Accumulating evidence is redefining the importance of neuron–glial interactions at synapses in the CNS. Astrocytes form “tripartite” complexes with presynaptic and postsynaptic structures and regulate synaptic transmission and plasticity. Despite our understanding of the importance of neuron–glial relationships in physiological contexts, little is known about the structural interplay between astrocytes and synapses. In the past, this has been difficult to explore because studies have been hampered by the lack of a system that preserves complex neuron–glial relationships observed in the brain. Here we present a system that can be used to characterize the intricate relationshipbetweenastrocyticprocessesandsynapticstructuresinsituusingorganotypichippocampalslices,apreparationthatretains the three-dimensional architecture of astrocyte–synapse interactions. Using time-lapse confocal imaging, we demonstrate that astro- cytes can rapidly extend and retract fine processes to engage and disengage from motile postsynaptic dendritic spines. Surprisingly, astrocytic motility is, on average, higher than its dendritic spine -
Modular Transport of Postsynaptic Density-95 Clusters and Association with Stable Spine Precursors During Early Development of Cortical Neurons
The Journal of Neuroscience, December 1, 2001, 21(23):9325–9333 Modular Transport of Postsynaptic Density-95 Clusters and Association with Stable Spine Precursors during Early Development of Cortical Neurons Oliver Prange,1 and Timothy H. Murphy1,2 Kinsmen Laboratory, Departments of 1Psychiatry and 2Physiology, University of British Columbia, Vancouver, British Columbia, Canada V6T 1Z3 The properties of filopodia and spines and their association spine membranes can move. Although processes bearing clus- with the postsynaptic density (PSD) protein PSD-95 were stud- ters were generally stable, in 8 DIV neurons, we observed that ied during early development of cultured cortical neurons using a subset (ϳ10%) of PSD-95/GFP clusters underwent rapid time-lapse confocal microscopy. Neurons were transfected modular translocation between filopodia–spines and dendritic with recombinant PSD-95 constructs fused to green fluores- shafts. We conclude that, during early synaptic maturation, cent protein (GFP) for, on average, either 8 d in vitro (DIV) or 14 prefabricated PSD-95 clusters are trafficked in a developmen- DIV. We find that, during 1 hr of imaging, filopodia and spines tally regulated process that is associated with filopodial stabi- bearing PSD-95/GFP clusters are significantly more stable (i.e., lization and synapse formation. do not turnover) than those lacking clusters. When present within a spine precursor, a PSD-95/GFP cluster appeared to Key words: development; dendritic spine; filopodium; gluta- nucleate a relatively stable structure around which filopodium– mate receptor; NMDA receptor; PSD-95 The postsynaptic density (PSD) protein PSD-95 is a founding associated protein) via GK] can tether PSD-95 and its binding member of the growing superfamily of PDZ (PSD-95–Disks partners to the intracellular tubulin and actin lattice, respectively large–zona occludens1/2) domain-containing proteins (Craven (Scannevin and Huganir, 2000). -
Coordinated Morphogenesis of Neurons and Glia
Available online at www.sciencedirect.com ScienceDirect Coordinated morphogenesis of neurons and glia Elizabeth R Lamkin and Maxwell G Heiman Glia adopt remarkable shapes that are tightly coordinated with The scope of the problem: highly dynamic and the morphologies of their neuronal partners. To achieve these localized morphological changes precise shapes, glia and neurons exhibit coordinated The intimate associations between glia and synapses morphological changes on the time scale of minutes and on exhibit highly dynamic morphological changes on the size scales ranging from nanometers to hundreds of microns. order of minutes [7–11]. Landmark studies using time- Here, we review recent studies that reveal the highly dynamic, lapse confocal imaging of rodent brain slices revealed that localized morphological changes of mammalian neuron–glia post-synaptic dendritic spines and astrocytic processes do contacts. We then explore the power of Drosophila and C. not change shape in perfect register, yet generally grow elegans models to study coordinated changes at defined or shrink together over time [7,9]. Remarkably, this neuron–glia contacts, highlighting the use of innovative genetic coordinated growth is achieved even though glia–spine and imaging tools to uncover the molecular mechanisms interactions undergo rapid structural changes, astrocytic responsible for coordinated morphogenesis of neurons processes tend to exhibit even greater motility than their and glia. dendritic spine counterparts, and the extent of glial coverage of spines varies [7]. Two recent, complementary studies provided evidence for a mechanism that may help to explain the coordinated growth of astrocytic processes and dendritic spines. Address Perez-Alvarez et al. and Bernardinelli et al. -
Gathering at the Nodes
RESEARCH HIGHLIGHTS GLIA Gathering at the nodes Saltatory conduction — the process by which that are found at the nodes of Ranvier, where action potentials propagate along myelinated they interact with Na+ channels. When the nerves — depends on the fact that voltage- authors either disrupted the localization of gated Na+ channels form clusters at the nodes gliomedin by using a soluble fusion protein of Ranvier, between sections of the myelin that contained the extracellular domain of sheath. New findings from Eshed et al. show neurofascin, or used RNA interference to that Schwann cells produce a protein called suppress the expression of gliomedin, the gliomedin, and that this is responsible for characteristic clustering of Na+ channels at the clustering of these channels. the nodes of Ranvier did not occur. The formation of the nodes of Ranvier is Aggregation of the domain of gliomedin specified by the myelinating cells, not the that binds neurofascin and NrCAM on the axons, and an important component of this surface of purified neurons also caused process in the peripheral nervous system the clustering of neurofascin, Na+ channels is the extension of microvilli by Schwann and other nodal proteins. These findings cells. These microvilli contact the axons at support a model in which gliomedin on the nodes, and it is here that the Schwann References and links Schwann cell microvilli binds to neurofascin ORIGINAL RESEARCH PAPER Eshed, Y. et al. Gliomedin cells express the newly discovered protein and NrCAM on axons, causing them to mediates Schwann cell–axon interaction and the molecular gliomedin. cluster at the nodes of Ranvier, and leading assembly of the nodes of Ranvier. -
Functional Consequences of Synapse Remodeling Following Astrocyte-Specific Regulation of Ephrin-B1 in the Adult Hippocampus
5710 • The Journal of Neuroscience, June 20, 2018 • 38(25):5710–5726 Cellular/Molecular Functional Consequences of Synapse Remodeling Following Astrocyte-Specific Regulation of Ephrin-B1 in the Adult Hippocampus Jordan Koeppen,1,2* XAmanda Q. Nguyen,1,3* Angeliki M. Nikolakopoulou,1 XMichael Garcia,1 XSandy Hanna,1 Simone Woodruff,1 Zoe Figueroa,1 XAndre Obenaus,4 and XIryna M. Ethell1,2,3 1Division of Biomedical Sciences, University of California Riverside School of Medicine, Riverside, California 92521, 2Cell, Molecular, and Developmental Biology Graduate program, University of California Riverside, California, 92521, 3Neuroscience Graduate Program, University of California Riverside, Riverside, California 92521, and 4Department of Pediatrics, University of California Irvine, Irvine, California 92350 Astrocyte-derived factors can control synapse formation and functions, making astrocytes an attractive target for regulating neuronal circuits and associated behaviors. Abnormal astrocyte-neuronal interactions are also implicated in neurodevelopmental disorders and neurodegenera- tive diseases associated with impaired learning and memory. However, little is known about astrocyte-mediated mechanisms that regulate learning and memory. Here, we propose astrocytic ephrin-B1 as a regulator of synaptogenesis in adult hippocampus and mouse learning behaviors. We found that astrocyte-specific ablation of ephrin-B1 in male mice triggers an increase in the density of immature dendritic spines and excitatory synaptic sites in the adult CA1 hippocampus. However, the prevalence of immature dendritic spines is associated with decreased evoked postsynaptic firing responses in CA1 pyramidal neurons, suggesting impaired maturation of these newly formed and potentially silent synapses or increased excitatory drive on the inhibitory neurons resulting in the overall decreased postsynaptic firing. -
Down-Regulation of Dendritic Spine and Glutamic Acid Decarboxylase 67 Expressions in the Reelin Haploinsufficient Heterozygous Reeler Mouse
Down-regulation of dendritic spine and glutamic acid decarboxylase 67 expressions in the reelin haploinsufficient heterozygous reeler mouse Wen Sheng Liu*, Christine Pesold*, Miguel A. Rodriguez*, Giovanni Carboni*, James Auta*, Pascal Lacor*, John Larson*, Brian G. Condie†, Alessandro Guidotti*, and Erminio Costa*‡ *Psychiatric Institute, Department of Psychiatry, College of Medicine, University of Illinois, Chicago, IL 60612; and †Institute of Molecular Medicine and Genetics, Departments of Medicine and Cellular Biology and Anatomy, Medical College of Georgia, Augusta, GA 30912 Contributed by Erminio Costa, December 22, 2000 Heterozygous reeler mice (HRM) haploinsufficient for reelin ex- heterozygote reeler mice (HRM) and in heterozygote GAD67 Ϸ press 50% of the brain reelin content of wild-type mice, but are knockout mice (HG67M) and compared them to their respective phenotypically different from both wild-type mice and homozy- wild-type background mice (WTM). In the present study, we gous reeler mice. They exhibit, (i) a down-regulation of glutamic have also quantified the number of neurons immunopositive for acid decarboxylase 67 (GAD67)-positive neurons in some but not reelin in the motor area of the frontoparietal cortex (FPC) of every cortical layer of frontoparietal cortex (FPC), (ii) an increase of HRM, as well as the total number of neurons immunopositive for neuronal packing density and a decrease of cortical thickness NeuN and the number of glial cells stained by Nissl (13) because of neuropil hypoplasia, (iii) a decrease of dendritic spine expressed in each of the six layers of this cortical area. In WTM, expression density on basal and apical dendritic branches of motor HRM, and HG67M, we have also quantified the laminar expres- FPC layer III pyramidal neurons, and (iv) a similar decrease in sion of GAD67-immunopositive neurons and the dendritic spine dendritic spines expressed on the basal dendrite branches of CA1 density expressed by pyramidal neurons of layer III FPC and of pyramidal neurons of the hippocampus. -
Sonic Hedgehog Signaling in Astrocytes Mediates Cell Type
RESEARCH ARTICLE Sonic hedgehog signaling in astrocytes mediates cell type-specific synaptic organization Steven A Hill1†, Andrew S Blaeser1†, Austin A Coley2, Yajun Xie3, Katherine A Shepard1, Corey C Harwell3, Wen-Jun Gao2, A Denise R Garcia1,2* 1Department of Biology, Drexel University, Philadelphia, United States; 2Department of Neurobiology and Anatomy, Drexel University College of Medicine, Philadelphia, United States; 3Department of Neurobiology, Harvard Medical School, Boston, United States Abstract Astrocytes have emerged as integral partners with neurons in regulating synapse formation and function, but the mechanisms that mediate these interactions are not well understood. Here, we show that Sonic hedgehog (Shh) signaling in mature astrocytes is required for establishing structural organization and remodeling of cortical synapses in a cell type-specific manner. In the postnatal cortex, Shh signaling is active in a subpopulation of mature astrocytes localized primarily in deep cortical layers. Selective disruption of Shh signaling in astrocytes produces a dramatic increase in synapse number specifically on layer V apical dendrites that emerges during adolescence and persists into adulthood. Dynamic turnover of dendritic spines is impaired in mutant mice and is accompanied by an increase in neuronal excitability and a reduction of the glial-specific, inward-rectifying K+ channel Kir4.1. These data identify a critical role for Shh signaling in astrocyte-mediated modulation of neuronal activity required for sculpting synapses. *For correspondence: DOI: https://doi.org/10.7554/eLife.45545.001 [email protected] †These authors contributed equally to this work Introduction Competing interests: The The organization of synapses into the appropriate number and distribution occurs through a process authors declare that no of robust synapse addition followed by a period of refinement during which excess synapses are competing interests exist. -
Presynaptic and Postsynaptic Scaffolds
NROXXX10.1177/1073858414523321The NeuroscientistZiv and Fisher-Lavie 523321research-article2014 Review The Neuroscientist 2014, Vol. 20(5) 439 –452 Presynaptic and Postsynaptic Scaffolds: © The Author(s) 2014 Reprints and permissions: sagepub.com/journalsPermissions.nav Dynamics Fast and Slow DOI: 10.1177/1073858414523321 nro.sagepub.com Noam E. Ziv1 and Arava Fisher-Lavie1 Abstract The development of methods to follow the dynamics of synaptic molecules in living neurons has radically altered our view of the synapse, from that of a generally static structure to that of a dynamic molecular assembly at steady state. This view holds not only for relatively labile synaptic components, such as synaptic vesicles, cytoskeletal elements, and neurotransmitter receptors, but also for the numerous synaptic molecules known as scaffolding molecules, a generic name for a diverse class of molecules that organize synaptic function in time and space. Recent studies reveal that these molecules, which confer a degree of stability to synaptic assemblies over time scales of hours and days, are themselves subject to significant dynamics. Furthermore, these dynamics are probably not without effect; wherever studied, these seem to be associated with spontaneous changes in scaffold molecule content, synaptic size, and possibly synaptic function. This review describes the dynamics exhibited by synaptic scaffold molecules, their typical time scales, and the potential implications to our understanding of synaptic function. Keywords synaptic tenacity, synaptic dynamics, synaptic scaffolds, FRAP, photoactivation Chemical synapses are sites of cell-cell contact special- held in register by trans-synaptic cell adhesion molecules ized for the rapid transmission of signals between neu- and extracellular matrix proteins. rons and their targets: muscles, glands, or other neurons. -
Alterations in Synaptic Density and Myelination in Response to Exposure to High-Energy Charged Particles
Received: 28 March 2018 Revised: 6 July 2018 Accepted: 21 August 2018 DOI: 10.1002/cne.24530 RESEARCH ARTICLE Alterations in synaptic density and myelination in response to exposure to high-energy charged particles Dara L. Dickstein1,2 | Ronan Talty2 | Erin Bresnahan2 | Merina Varghese2 | Bayley Perry1 | William G. M. Janssen2 | Allison Sowa2 | Erich Giedzinski3 | Lauren Apodaca3 | Janet Baulch3 | Munjal Acharya3 | Vipan Parihar3 | Charles L. Limoli3 1Uniformed Services University of Health Sciences, Bethesda, Maryland Abstract 2Fishberg Department of Neuroscience, Icahn High-energy charged particles are considered particularly hazardous components of the space School of Medicine at Mount Sinai, New York, radiation environment. Such particles include fully ionized energetic nuclei of helium, silicon, New York and oxygen, among others. Exposure to charged particles causes reactive oxygen species pro- 3 Department of Radiation Oncology, duction, which has been shown to result in neuronal dysfunction and myelin degeneration. Here University of California, Irvine, California we demonstrate that mice exposed to high-energy charged particles exhibited alterations in Correspondence Dara L. Dickstein, Department of Pathology, dendritic spine density in the hippocampus, with a significant decrease of thin spines in mice Uniformed Services University of the Health exposed to helium, oxygen, and silicon, compared to sham-irradiated controls. Electron micros- Sciences, Bethesda, MD 20814. copy confirmed these findings and revealed a significant decrease in overall synapse density and Email: [email protected] in nonperforated synapse density, with helium and silicon exhibiting more detrimental effects and Charles L. Limoli, Department of Radiation than oxygen. Degeneration of myelin was also evident in exposed mice with significant changes Oncology, University of California, Irvine, CA in the percentage of myelinated axons and g-ratios. -
Activity in Grafted Human Ips Cell–Derived Cortical Neurons Integrated in Stroke-Injured Rat Brain Regulates Motor Behavior
Activity in grafted human iPS cell–derived cortical neurons integrated in stroke-injured rat brain regulates motor behavior Sara Palma-Tortosaa,1, Daniel Torneroa,b,1, Marita Grønning Hansena, Emanuela Monnia, Mazin Hajya, Sopiko Kartsivadzea,c, Sibel Aktaya, Oleg Tsupykovd,e, Malin Parmarf, Karl Deisserothg, Galyna Skibod,e, Olle Lindvalla, and Zaal Kokaiaa,2 aLaboratory of Stem Cells and Restorative Neurology, Lund Stem Cell Center, Lund University, SE-22184 Lund, Sweden; bLaboratory of Stem Cells and Regenerative Medicine, Institute of Neurosciences, University of Barcelona, ES-08036 Barcelona, Spain; cDepartment of Neurology, Iv. Javakhishvili Tbilisi State University, 0179 Tbilisi, Georgia; dDepartment of Cytology, Bogomoletz Institute of Physiology, 01024 Kyiv, Ukraine; eLaboratory of Cell and Tissue Cultures, State Institute of Genetic and Regenerative Medicine, 04114 Kyiv, Ukraine; fDevelopmental and Regenerative Neurobiology, Department of Experimental Medical Science, Lund Stem Cell Center, Lund University, SE-22184 Lund, Sweden; and gDepartment of Bioengineering, Stanford University, Stanford, CA 94305 Edited by Anders Björklund, Lund University, Lund, Sweden, and approved March 9, 2020 (received for review January 14, 2020) Stem cell transplantation can improve behavioral recovery after induced pluripotent stem (iPS) cells, into the cerebral cortex ad- stroke in animal models but whether stem cell–derived neurons jacent to an ischemic lesion induced by distal middle cerebral become functionally integrated into stroke-injured brain circuitry artery occlusion (dMCAO) leads to improvement of sensorimotor is poorly understood. Here we show that intracortically grafted deficits (7). Grafted neurons receive synaptic inputs from thala- human induced pluripotent stem (iPS) cell–derived cortical neurons mocortical afferents in the stroke-affected host brain (8) and alter send widespread axonal projections to both hemispheres of rats their activity in response to physiological sensory stimuli. -
Regional Diversity in the Postsynaptic Proteome of the Mouse Brain
bioRxiv preprint doi: https://doi.org/10.1101/368910; this version posted July 13, 2018. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under aCC-BY-NC-ND 4.0 International license. Regional diversity in the postsynaptic proteome of the mouse brain Marcia Roy1*, Oksana Sorokina2*, Colin McLean2, Silvia Tapia-González3, Javier DeFelipe3, J. Douglas Armstrong2 and Seth G. N. Grant1 * equal contribution Author Affiliations: 1. Centre for Clinical Brain Sciences, University of Edinburgh, Edinburgh EH16 4SB, United Kingdom 2. School of Informatics, University of Edinburgh, Edinburgh EH8 9AB, United Kingdom 3. Instituto Cajal (CSIC), Ave. Dr. Arce 37, 28002 Madrid, Spain Correspondence: [email protected] 1 bioRxiv preprint doi: https://doi.org/10.1101/368910; this version posted July 13, 2018. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under aCC-BY-NC-ND 4.0 International license. Abstract: The proteome of the postsynaptic terminal of excitatory synapses comprises over one thousand proteins in vertebrate species and plays a central role in behavior and brain disease. The brain is organized into anatomically distinct regions and whether the synapse proteome differs across these regions is poorly understood. Postsynaptic proteomes were isolated from seven forebrain and hindbrain regions in mice and their composition determined using proteomic mass spectrometry. Seventy-four percent of proteins showed differential expression and each region displayed a unique compositional signature. -
Coupling of Terminal Differentiation Deficit with Neurodegenerative Pathology in Vps35-Deficient Pyramidal Neurons
Cell Death & Differentiation (2020) 27:2099–2116 https://doi.org/10.1038/s41418-019-0487-2 ARTICLE Coupling of terminal differentiation deficit with neurodegenerative pathology in Vps35-deficient pyramidal neurons 1 1,2,3 2,3 1,2 3 1,2 1,2 Fu-Lei Tang ● Lu Zhao ● Yang Zhao ● Dong Sun ● Xiao-Juan Zhu ● Lin Mei ● Wen-Cheng Xiong Received: 20 June 2019 / Revised: 13 December 2019 / Accepted: 17 December 2019 / Published online: 6 January 2020 © The Author(s), under exclusive licence to ADMC Associazione Differenziamento e Morte Cellulare 2020. This article is published with open access Abstract Vps35 (vacuolar protein sorting 35) is a key component of retromer that regulates transmembrane protein trafficking. Dysfunctional Vps35 is a risk factor for neurodegenerative diseases, including Parkinson’s and Alzheimer’s diseases. Vps35 is highly expressed in developing pyramidal neurons, and its physiological role in developing neurons remains to be explored. Here, we provide evidence that Vps35 in embryonic neurons is necessary for axonal and dendritic terminal differentiation. Loss of Vps35 in embryonic neurons results in not only terminal differentiation deficits, but also neurodegenerative pathology, such as cortical brain atrophy and reactive glial responses. The atrophy of neocortex appears to be in association with increases in neuronal death, autophagosome proteins (LC3-II and P62), and neurodegeneration associated proteins (TDP43 and ubiquitin-conjugated proteins). Further studies reveal an increase of retromer cargo protein, sortilin1 (Sort1), in lysosomes of Vps35-KO neurons, and lysosomal dysfunction. Suppression of Sort1 diminishes Vps35- KO-induced dendritic defects. Expression of lysosomal Sort1 recapitulates Vps35-KO-induced phenotypes.