Ultrastructural Study of the Granule Cell Domain of the Cochlear Nucleus in Rats: Mossy Fiber Endings and Their Targets

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Consensus Paper: Cerebellar Development

Cerebellum DOI 10.1007/s12311-015-0724-2 CONSENSUS PAPER Consensus Paper: Cerebellar Development Ketty Leto1,2 & Marife Arancillo3 & Esther B. E. Becker4 & Annalisa Buffo1,2 & Chin Chiang5 & Baojin Ding6 & William B. Dobyns 7,8 & Isabelle Dusart9,10 & Parthiv Haldipur7 & Mary E. Hatten11 & Mikio Hoshino12 & Alexandra L. Joyner13 & Masanobu Kano14 & Daniel L. Kilpatrick6 & Noriyuki Koibuchi15 & Silvia Marino16 & Salvador Martinez17 & Kathleen J. Millen7 & Thomas O. Millner16 & Takaki Miyata18 & Elena Parmigiani1,2 & Karl Schilling19 & Gabriella Sekerková20 & Roy V. Sillitoe3 & Constantino Sotelo21 & Naofumi Uesaka14 & Annika Wefers 22 & Richard J. T. Wingate23 & Richard Hawkes24 # The Author(s) 2015. This article is published with open access at Springerlink.com Abstract The development of the mammalian cerebellum is processes of cerebellar ontogenesis, highlighting the neuro- orchestrated by both cell-autonomous programs and inductive genic strategies used by developing progenitors, the genetic environmental influences. Here, we describe the main programs involved in cell fate specification, the progressive * Ketty Leto 10 Centre National de la Recherche Scientifique, CNRS, UMR8246, [email protected] INSERM U1130, Neuroscience Paris Seine, France, 75005 Paris, France 11 Laboratory of Developmental Neurobiology, The Rockefeller 1 Department of Neuroscience Rita Levi Montalcini, University of University, New York, NY 10065, USA Turin, via Cherasco 15, 10026 Turin, Italy 12 Department of Biochemistry and Cellular Biology, National Institute
Purkinje Cell Migration Disorder By

CEREBELLAR CORTICOGENESIS IN THE LYSOSOMAL ACID PHOSPHATASE (ACP2) MUTANT MICE: PURKINJE CELL MIGRATION DISORDER BY NILOUFAR ASHTARI A Thesis Submitted to the Faculty of Graduate Studies of The University of Manitoba in Partial Fulfilment of the Requirements for the Degree of MASTER OF SCIENCE Department of Human Anatomy and Cell Science University of Manitoba Winnipeg, Manitoba Copyright © 2017 by Niloufar Ashtari 1 Abstract In a mutant mouse called nax as the result of mutation in Lysosomal Acid phosphatase (Acp2), layers of the cerebellar cortex are impaired and monolayer Purkinje cells (Pcs) turn to multi-layered Pcs that ectopically invade the molecular layer. We investigated reelin-Dab1 signaling as an important pathway for Pcs migration and monolayer formation in cerebellum. ERK1/2 is a member of mitogen activated kinases family and suggested to be a downstream of reelin signaling. We hypothesize that the establishment of mono-layered Pcs rely on reelin through ERK1/2 pathway. Acp2 mutant mice were used for this study and molecular expression and distribution were assessed by immunohistochemistry, RT-PCR, western blotting, and cell culture. Results suggest that reelin may modulate the ERK1/2 expression, thus lower expression of reelin and higher phosphorylation of Dab1 leads to over expression of the ERK1/2 that causes the Pcs to over migrate and form multilayer in nax cerebellar cortex. i TABLE OF CONTENTS LISTOFABBREVIATIONS………………………………………………..…... IV LIST OF TABLES……………………………………...…………………...….. Vii LIST OF FIGURES…………………………………………………….………. Viii CHAPTER 1: INTRODUCTION…………………………………….………… 1 1.1 Cerebellum ……………………………………………………........………. 1 1.2 Development of Central Nervous System………………………………….. 2 1.3 Development of the cerebellum………………………………….................. 3 1.4 Specification of cerebellar germinal zones………………………………….
Granule Cell Synapses of Rat Cerebellum: Experimental Observations and Theoretical Predictions

Articles in PresS. J Neurophysiol (October 5, 2005). doi:10.1152/jn.00696.2005 1 LTP regulates burst initiation and frequency at mossy fiber – granule cell synapses of rat cerebellum: experimental observations and theoretical predictions Thierry Nieus1,2, Elisabetta Sola1,4, Jonathan Mapelli1, Elena Saftenku3, Paola Rossi1, Egidio D’Angelo1,2,* 1 Dept. of Cellular-Molecular Physiological and Pharmacological Sciences (University of Pavia) and INFM, Via Forlanini 6, I-27100, Pavia, Italy. 2 Dept. of Functional and Evolutionary Biology (University of Parma), Parco Area delle Scienze 11a, I-34100, Parma, Italy. 3 Dept. of General Physiology of Nervous System, A.A. Bogomoletz Institute of Physiology Bogomoletz St., 4, 01024, Kiev-24, Ukraine 4 present address: Dept. of Biophysics, SISSA, via Beirut 4, I-34014, Trieste, Italy * To whom correspondence should be addressed at [email protected] Key-words. LTP, Synaptic plasticity, Presynaptic mechanisms, Cerebellum, Granule cells Running title. LTP and bursting in the cerebellum Acknowledgments. This work was supported by projects of the European Community (CEREBELLUM QLG3-CT-2001-02256 and SPIKEFORCE IST-2001-35271), of MIUR and INFM of Italy to ED. ABSTRACT Long-term potentiation (LTP) is a synaptic change supposed to provide the cellular basis for learning and memory in brain neuronal circuits. Although specific LTP expression mechanisms could be critical to determine the dynamics of repetitive neurotransmission, this important issue remained largely unexplored. In this paper we have performed whole-cell patch-clamp recordings of mossy fiber – granule cell LTP in acute rat cerebellar slices and investigated its computational implications with a mathematical model. During LTP, stimulation with short impulse trains at 100 Hz revealed earlier initiation of granule cell spike bursts and a smaller non-significant spike frequency increase.
Three-Dimensional Morphology of Cerebellar Protoplasmic Islands

Scanning Microscopy Volume 5 Number 2 Article 16 2-16-1991 Three-Dimensional Morphology of Cerebellar Protoplasmic Islands and Proteoglycan Content of Mossy Fiber Glomerulus: A Scanning and Transmission Electron Microscope Study O. J. Castejón Universidad del Zulia, Venezuela H. V. Castejón Universidad del Zulia, Venezuela Follow this and additional works at: https://digitalcommons.usu.edu/microscopy Part of the Biology Commons Recommended Citation Castejón, O. J. and Castejón, H. V. (1991) "Three-Dimensional Morphology of Cerebellar Protoplasmic Islands and Proteoglycan Content of Mossy Fiber Glomerulus: A Scanning and Transmission Electron Microscope Study," Scanning Microscopy: Vol. 5 : No. 2 , Article 16. Available at: https://digitalcommons.usu.edu/microscopy/vol5/iss2/16 This Article is brought to you for free and open access by the Western Dairy Center at DigitalCommons@USU. It has been accepted for inclusion in Scanning Microscopy by an authorized administrator of DigitalCommons@USU. For more information, please contact [email protected]. Scanning Microscopy , Vol. 5, No . 2, 1991 (Pages 477-494) 0891 -7035/91$3.00+ .00 Scanning Microscopy International , Chicago (AMF O'Hare) , IL 60666 USA THREE-DI MENSIONAL MORPHOLOGYOF CEREBELLAR PROTOPLASMIC ISLANDS AND PROTEOGLYCANCO NTENT OF MOSSY FIBER GLOMERULUS: A SCANNING AND TRANSMISSION ELECTRON MICROSCOPE STUDY 0. J . Cas tejon and H. V. Castejon Institute de Investigac1ones Biologicas. Facultad de Medicina . Universidad de l Zulia. Apart ado 526, Mara ca ibo, Venezu ela (Received for publication May 2, 1990 , and in revised form February 16, 1991) Abstract Introduction The present rev , ew summarizes the outer and The cerebellar protoplasmatic islands and inner surface features of mossy f ib er glomeru li the cerebellar glomeruli were studied at light 1n vertebra te cerebellar granular la yer as seen microscope level by Denissenko ( 18771, Ramon y by conv en t i ona l scanning electron microscopy Cajal ( 1889, 19551, Retzius ( 1892a,b), Lugaro <SEMI and SEM fre eze -f ra cture method .
Astroglial Glutamate Transporters in the Brain: Regulating Neurotransmitter Homeostasis and Synaptic Transmission

Journal of Neuroscience Research 95:2140–2151 (2017) Review Astroglial Glutamate Transporters in the Brain: Regulating Neurotransmitter Homeostasis and Synaptic Transmission Ciaran Murphy-Royal,1,2 Julien Dupuis,2,3 Laurent Groc,2,3 and Stephane H. R. Oliet 1,2 1Neurocentre Magendie, Inserm U1215, Bordeaux, France 2Universite de Bordeaux, Bordeaux, France 3Interdisciplinary Institute for Neuroscience, CNRS UMR 5297, Bordeaux, France Astrocytes, the major glial cell type in the central nervous compartments. As an example, the extracellular glutamate system (CNS), are critical for brain function and have concentration is maintained at low values lying most like- been implicated in various disorders of the central ner- ly below 100 nM (Hamberger and Nystrom,€ 1984; vous system. These cells are involved in a wide range of Cavelier and Attwell, 2005; Herman and Jahr, 2007), cerebral processes including brain metabolism, control of while it is much more concentrated inside cells. As there central blood flow, ionic homeostasis, fine-tuning synap- are no extracellular enzymes degrading glutamate, this tic transmission, and neurotransmitter clearance. Such low extracellular concentration can be fully accounted for varied roles can be efficiently carried out due to the inti- by specific transporters, which are widely expressed mate interactions astrocytes maintain with neurons, the throughout the brain (Furuta et al., 1997). Glutamate vasculature, as well as with other glial cells. Arguably, one transporters working under physiological conditions have of the most important functions of astrocytes in the brain the capacity to establish concentration gradients of 106 is their control of neurotransmitter clearance. This is across the plasma membrane, theoretically resulting in a particularly true for glutamate whose timecourse in the glutamate concentration of 10 nM extracellularly and 10 synaptic cleft needs to be controlled tightly under physio- mM intracellularly (Zerangue and Kavanaugh, 1996a).
Staining of Cerebellar Cortex Granular Layer Interneurons with Natural Dye of Madder Anneh Mohammad Gharravi

Gharravi Cerebellum & Ataxias (2016) 3:12 DOI 10.1186/s40673-016-0050-6 RESEARCH Open Access Staining of cerebellar cortex granular layer interneurons with natural dye of Madder Anneh Mohammad Gharravi Abstract Background: The objective of the present study was an investigation of root Rubia Tinctorum (Madder) as a natural dye to identification of granular layer interneurons of the rat cerebellum. Methods: Seven to ten micrometre sections were collected from the cerebellum and stained only with Madder for 2, 24 and 48 h. Other sections were stained with Madder then with hematoxyllin, cresyl violet, eosin, light green. Microscopic identification of cells was performed based on cell morphology, reaction and binding of with the dye. All data were expressed as mean ± SD in and significance was set at p ≤0.05. Results: Madder with alum as mordant resulted a deep red staining of interneurons. Unipolar brush cells (UBCs) were observed with a cell body diameter intermediate between granule and Golgi cells in the superficial layer of the granular layer. Golgi cells were identified almost as large as Purkinje cells with irregular rounded or polygonal morphology. Lugaro cells were observed as spindle-shaped cells adjacent to Purkinje layer. Conclusion: Results of the present study showed that mader could stain granular layer interneurons in cerebellum cortex of rat. Keywords: Madder, Cerebellum, Unipolar brush cells, Lugaro cell, Golgi neurons Background with all cerebellar cortical neurons and fibers and they Histologically, the cerebellar cortex is divided into three function as inhibitory interneurons. These spindle-shaped layers: the molecular, the Purkinje and the granular cells locate just underneath the Purkinje cell layer are layers.
Svetla P. Pencheva, Emilyan A. Ivanov Summary ULTRASTRUCTURAL

J Biomed Clin Res Volume 6 Number 1, 2013 DOI: 10.1515/jbcr-2015-0095 Original Article ULTRASTRUCTURAL STUDY OF THE SYNAPTIC GLOMERULI IN THE RAT'S COCHLEAR NUCLEUS Svetla P. Pencheva, Summary Emilyan A. Ivanov The granule cell domain of the cochlear nuclear complex Department of Anatomy, Histology, contains interneurons, which are the targets for Citology and Biology nonprimary auditory inputs from the superior olivary complex, inferior colliculus, auditory cortex, cuneate and Medical University – Pleven trigeminal nuclei of the somatosensory system. The Bulgaria cellular targets of the non-primary projections are unknown due to a lack of information regarding postsynaptic profiles in the granule cell areas. In the present paper, we examined the synaptic relationships between a heterogeneous class of large synaptic terminals, called mossy fibers and their targets within subdivisions of the granule cell domain. During the late stage of postnatal development, we observed heterogenous groups of complex synaptic glomeruli. Using electron microscopy, we provide evidence for ultrastructural features of dendrites that receive input from the mossy fibers. The distinct synaptic relations between mossy fibers and dendrites of microneurons further imply fundamentally separate roles in processing of acoustic signals. Key wards: cochlear nucleus, granule cell domain, synaptic glomerulus Introduction The granule cell domain of the cochlear nucleus Corresponding Autor: comprises up to seven different subdivisions [1]. Svetla P. Pencheva These subdivisions are found around the core of the Sector of Anatomy, Histology and ventral cochlear nucleus (VCN) and the dorsal Cytology cochlear nucleus ( DCN), including the superficial Medical University-Pleven layer of the VCN, the lamina dividing DCN from Pleven, 5800 Bulgaria VCN, the subpeduncular dorsal corner of the VCN, е-mail: [email protected] the dorsal strial corner of the DCN, and layer II of the DCN [2, 3].
Morphogenetic Plasticity of Neuronal Elements in Cerebellar Glomeruli During Deafferentation-Induced Synaptic Reorganization J6zsefhhmori, Robert L

(C)Freund Publishing House Ltd., 1997 Morphogenetic Plasticity of Neuronal Elements in Cerebellar Glomeruli during Deafferentation-Induced Synaptic Reorganization J6zsefHhmori, Robert L. Jakab and J6zsefTakb.cs Department ofAnatomy, Laboratory ofNeurobiology, Semmelweis University, Medical School, Budapest, Hungary, H-1094; Section ofNeurobiology, Yale University School ofMedicine, New Haven, CT, USA SUMMARY represented only one-fifth of all synaptic junctions. The quantitative data of the Reorganization of the cerebellar glomerulus, reorganized cerebellar glomerulus demonstrate the main synaptic complex within the granule both a remarkable constancy and a plasticity of cell layer, was investigated using quantitative the excitatory granule cells and inhibitory Golgi morphological techniques. All afferents to the neurons building up this synaptic complex. cerebellar cortex, including mossy-fibers, were Constancy (the preservation of certain specific surgically destroyed by undercutting the structural features) is represented by an cerebellar vermis. Fifteen days after the eventually unchanged number of dendrites and operation, which resulted in the removal of the synaptic junctions within the deafferented main excitatory afferent to the glomerulus, a glomerulus. Such constancy was made possible, significant reorganization of the whole synaptic however, by the morphogenetic plasticity of complex was observed, whereas the structural both nerve-cell types to produce new, dendro- integrity of the glomerulus was remarkably well dendritic and axo-dendritic synapses to preserved. This was indicated by the compensate for the loss of mossy-fiber synapses. observation that the number of granule cell dendrites per glomerulus), as well as the (50 KEY number of dendritic digits (210 per WORDS glomerulus) bearing most of the 230 synaptic eerebellar cortex, deafferentation, synaptic junctions per glomerulus, did not change EM significantly after mossy-fiber degeneration.
FIRST PROOF Cerebellum

Article Number : EONS : 0736 GROSS ANATOMY Cerebellum Cortex The cerebellar cortex is an extensive three-layered sheet with a surface approximately 15 cm laterally THE HUMAN CEREBELLUM (‘‘little brain’’) is a and 180 cm rostrocaudally but densely folded around significant part of the central nervous system both three pairs of nuclei. The cortex is divided into three in size and in neural structure. It occupies approxi- transverse lobes: Anterior and posterior lobes are mately one-tenth of the cranial cavity, sitting astride separated by the primary fissure, and the smaller the brainstem, beneath the occipital cortex, and flocculonodular lobe is separated by the poster- contains more neurons than the whole of the cerebral olateral fissure (Fig. 1). The anterior and posterior cortex. It consists of an extensive cortical sheet, lobes are folded into a number of lobules and further densely folded around three pairs of nuclei. The folded into a series of folia. This transverse organiza- cortex contains only five main neural cell types and is tion is then divided at right angles into broad one of the most regular and uniform structures in the longitudinal regions. The central vermis, named for central nervous system (CNS), with an orthogonal its worm-like appearance, is most obvious in the ‘‘crystalline’’ organization. Major connections are posterior lobe. On either side is the paravermal or made to and from the spinal cord, brainstem, and intermediate cortex, which merges into the lateral sensorimotor areas of the cerebral cortex. hemispheres. The most common causes of damage to the cerebellum are stroke, tumors, or multiple sclerosis.
Cerebellar Cortical Neuron Responses Evoked from the Spinal Border Cell Tract

Cerebellar cortical neuron responses evoked from the spinal border cell tract. Geborek, Pontus; Spanne, Anton; Bengtsson, Fredrik; Jörntell, Henrik Published in: Frontiers in Neural Circuits DOI: 10.3389/fncir.2013.00157 2013 Link to publication Citation for published version (APA): Geborek, P., Spanne, A., Bengtsson, F., & Jörntell, H. (2013). Cerebellar cortical neuron responses evoked from the spinal border cell tract. Frontiers in Neural Circuits, 7, [157]. https://doi.org/10.3389/fncir.2013.00157 Total number of authors: 4 General rights Unless other specific re-use rights are stated the following general rights apply: Copyright and moral rights for the publications made accessible in the public portal are retained by the authors and/or other copyright owners and it is a condition of accessing publications that users recognise and abide by the legal requirements associated with these rights. • Users may download and print one copy of any publication from the public portal for the purpose of private study or research. • You may not further distribute the material or use it for any profit-making activity or commercial gain • You may freely distribute the URL identifying the publication in the public portal Read more about Creative commons licenses: https://creativecommons.org/licenses/ Take down policy If you believe that this document breaches copyright please contact us providing details, and we will remove access to the work immediately and investigate your claim. LUND UNIVERSITY PO Box 117 221 00 Lund +46 46-222 00 00 Download date: 04. Oct. 2021 ORIGINAL RESEARCH ARTICLE published: 08 October 2013 NEURAL CIRCUITS doi: 10.3389/fncir.2013.00157 Cerebellar cortical neuron responses evoked from the spinal border cell tract Pontus Geborek, Anton Spanne, Fredrik Bengtsson and Henrik Jörntell* Neural Basis of Sensorimotor Control, Department of Experimental Medical Science, Lund University, Lund, Sweden Edited by: Spinocerebellar systems are likely to be crucial for cerebellar hallmark functions such Egidio D’Angelo, University of Pavia, as coordination.
SYNAPTIC REGULATION of TWO INTERNEURON MICROCIRCUITS in CEREBELLUM-LIKE STRUCTURES by Hsin-Wei Lu a DISSERTA

PRE- AND POST- SYNAPTIC REGULATION OF TWO INTERNEURON MICROCIRCUITS IN CEREBELLUM-LIKE STRUCTURES By Hsin-Wei Lu A DISSERTATION Presented to the NeurosCience Graduate Program and the Oregon Health & ScienCe University School of MediCine in partial fulfillment of the requirements for the degree of DoCtor of Philosophy June 2016 TABLE OF CONTENTS ACKNOWLEDGEMENTS…………………………………………………………………………………………………iii ABSTRACT…………………………………………………………………………………………………………………… iv LIST OF FIGURES ………………………………………………………………………………………………………… vi LIST OF TABLES…………………………………………………………………………………………………………... vii INTRODUCTION…………………………………………………………………………………………………………… 1 CHAPTER 1. SPONTANEOUS SPIKIG DEFINES CONVERGENT RATIOS IN AN INHIBITORY CIRCUIT……………………………………………………………………………………………………………………… 14 AbstraCt …………………………………………………………………………………………………………… 15 Significance Statement …………………………………………………………………………………….. 16 IntroduCtion …………………………………………………………………………………………………….. 16 Methods …………………………………………………………………………………………………………... 18 Results …………………………………………………………………………………………………………….. 24 Rapid short-term depression at cartwheel cell synapse …………………………................. 24 Single-pool vesicle deletion model is unable to explain synaptic depression……….....25 Two-pool vesicle depletion model accounts for synaptic depression …………………... 26 Ca2+-dependent recovery dose not mediate transmission during depression ............. 30 Low-Pr pool dominates release during spontaneous activity……………………………… 31 Small convergence ratio in the cartwheel-fusiform circuit ………………………………… 32 Size of effective convergence
Forward Signaling by Unipolar Brush Cells in the Mouse Cerebellum

Cerebellum DOI 10.1007/s12311-015-0693-5 ORIGINAL PAPER Forward Signaling by Unipolar Brush Cells in the Mouse Cerebellum Stijn van Dorp1 & Chris I. De Zeeuw 1,2 # The Author(s) 2015. This article is published with open access at Springerlink.com Abstract Unipolar brush cells (UBCs) are glutamatergic in- Introduction terneurons prominently present in the granular layer of the vestibulocerebellum. UBCs engage in extensive synaptic con- Forward processing, in particular the absence of recurrent tact with a single presynaptic mossy fiber and signal to down- excitation, is a defining feature of cerebellar architecture stream granule cells through an elaborate network of mossy and computation. In the granular layer of the fiber-like axons. Ultrastructural examinations and electro- vestibulocerebellum, unipolar brush cells (UBCs) provide physiological recordings in organotypic slice cultures have a powerful forward excitatory action onto granule cells indicated that UBCs target not only granule cells but also other through a cortex-intrinsic network of mossy fiber-like UBCs, thus forming chains of two or perhaps more intercon- axons [1, 2]. UBCs are characterized by an elaborate nected UBCs. In this report, we show recordings of spontane- brush-like dendrite (Fig. 1a) that forms an unusually exten- ous and evoked (di)synaptic events in granule cells and UBCs sive synaptic contact with a single presynaptic mossy fiber in fresh cerebellar slices from juvenile mice (5–7 weeks). The rosette [3]. This highly specialized configuration has been patterns of arrival of synaptic events were consistent with the proposed to facilitate prolonged entrapment of glutamate presence of a presynaptic UBC, and recordings from UBCs in the synaptic cleft, underlying complex temporal trans- displayed spontaneous protracted synaptic events characteris- formations of incoming mossy fiber signals [4, 5].