Variable Timing of Synaptic Transmission in Cerebellar Unipolar Brush Cells
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Ultrastructural Study of the Granule Cell Domain of the Cochlear Nucleus in Rats: Mossy Fiber Endings and Their Targets
THE JOURNAL OF COMPARATIVE NEUROLOGY 369~345-360 ( 1996) Ultrastructural Study of the Granule Cell Domain of the Cochlear Nucleus in Rats: Mossy Fiber Endings and Their Targets DIANA L. WEEDMAN, TAN PONGSTAPORN, AND DAVID K. RYUGO Center for Hearing Sciences, Departments of Otolaryngoloby-Head and Neck Surgery and Neuroscience, Johns Hopkins University School of Medicine, Baltimore, Maryland 2 1205 ABSTRACT The principal projection neurons of the cochlear nucleus receive the bulk of their input from the auditory nerve. These projection neurons reside in the core of the nucleus and are surrounded by an external shell, which is called the granule cell domain. Interneurons of the cochlear granule cell domain are the target for nonprimary auditory inputs, including projections from the superior olivary complex, inferior colliculus, and auditory cortex. The granule cell domain also receives projections from the cuneate and trigeminal nuclei, which are first-order nuclei of the somatosensory system. The cellular targets of the nonprimary projections are mostly 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 known as the lamina and superficial layer. By using light and electron microscopic methods in these subdivisions, we provide evidence for three different neuron classes that receive input from the mossy fibers: granule cells, unipolar brush cells, and a previously undescribed class called chestnut cells. The distinct synaptic relations between mossy fibers and members of each neuron class further imply fundamentally separate roles for processing acoustic signals. -
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…………………………………. -
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. -
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]. -
The Developmental Genetics of the Cerebellum and the Genetic Bases of Known Cerebellar Disorders
THE DEVELOPMENTAL GENETICS OF THE CEREBELLUM AND THE GENETIC BASES OF KNOWN CEREBELLAR DISORDERS A Review of Developmental Genetics of the Cerebellum and the Genetic Bases of known Cerebellar Disorders Olakada Favour Adamba 17/MHS01/254 Department of Medicine and Health Sciences College of Medicine and Health Sciences Afe Babalola University ANA 303: Neuroanatomy July, 2020 The Developmental Genetics of Cerebellum and the Genetic Bases of known Cerebellar Disorders: A Literature Review Olakada Favour Adamba1 Abstract The internal structure of the cerebellum is an intriguing paradox; its cytoarchitecture is relatively simple compared to the connections between its neurons, which are wired into a complex array of gene expression domains and functional circuits. The genetic research of cerebellar development has provided a great deal of information about the molecular events directing the formation of the cerebellum. The developmental mechanisms that coordinate the establishment of cerebellar structure and circuitry provide a powerful model for understanding how a functional brain develops and its significance in cerebellar disorders and diseases. The cellular makeup of the cerebellum is derived from two primary germinal matrices (the ventricular zone and a specialized germinal matrix called the rhombic lip). Each matrix/zone expresses a specific set of genes that establish the cell lineages within the cerebellar anlage. Then, cohorts of differentiated projection neurons and interneuron progenitors migrate into the developing cerebellum. thereafter, a number of remarkable patterning events occur. Altogether, structural and molecular organisations are thought to support the proper connectivity between incoming afferent projections and their target cells. Key words: Cerebellum, circuitry, genetic, development, disorders. I. Introduction The cerebellum (‘little brain’) resides at the anterior end of the hindbrain and is classically defined by its role in sensory-motor processing (Buckner, 2013). -
Early Onset of Ataxia in Moonwalker Mice Is Accompanied by Complete Ablation of Type II Unipolar Brush Cells and Purkinje Cell Dysfunction
The Journal of Neuroscience, December 11, 2013 • 33(50):19689–19694 • 19689 Brief Communications Early Onset of Ataxia in Moonwalker Mice Is Accompanied by Complete Ablation of Type II Unipolar Brush Cells and Purkinje Cell Dysfunction Gabriella Sekerkova´,1,2* Jin-Ah Kim,1* Maximiliano J. Nigro,1 Esther B. E. Becker,3 Jana Hartmann,4 Lutz Birnbaumer,5 Enrico Mugnaini,1,2 and Marco Martina1 Departments of 1Physiology and 2Cell and Molecular Biology, Northwestern University Feinberg School of Medicine, Chicago, Illinois 60611, 3Department of Physiology, Anatomy, and Genetics, MRC Functional Genomics Unit, Oxford OX1 3PT, United Kingdom, 4Institute of Neuroscience, Technical University Munich, 80802 Munich, Germany, and 5Laboratory of Neurobiology, National Institute of Environmental Health Sciences, National Institutes of Health, Department of Health and Human Services, Durham, North Carolina 27709 Transient receptor potential “canonical” cation channels (TRPC) are involved in many cellular activities, including neuronal synaptic transmission. These channels couple lipid metabolism, calcium homeostasis, and electrophysiological properties as they are calcium permeable and activated through the phospholipase C pathway and by diacylglycerol. The TRPC3 subunit is abundantly expressed in Purkinje cells (PCs), where it mediates slow metabotropic glutamate receptor-mediated synaptic responses. Recently, it has been shown that heterozygous moonwalker mice, which are a model of cerebellar ataxia, carry a dominant gain-of-function mutation (T635A) in the TRPC3 gene. This mutation leads to PC loss and dysmorphism, which have been suggested to cause the ataxia. However, the ataxic phenotype is present from a very early stage (before weaning), whereas PC loss does not appear until several months of age. -
Sensing How to Balance
INSIGHT CEREBELLUM Sensing how to balance How does the inner ear communicate with the cerebellar cortex to maintain balance and posture? FABRICE ANGO AND RAPHAE¨ L DOS REIS Both the primary and secondary afferents Related research article Balmer TS, Trus- form synapses with neurons called granule cells sell LO. 2019. Selective targeting of unipo- in the cerebellum: granule cells are the most lar brush cell subtypes by cerebellar mossy numerous excitatory neurons in the brain fibers. eLife 8:e44964. DOI: 10.7554/eLife. (Chadderton et al., 2004). A single mossy fiber 44964 can activate hundreds of granule cells which, in turn, form synapses with the dendrites of Pur- kinje cells. These cells are the sole output neu- rons from the cerebellar cortex and they have a crucial role in motor learning. eeping your head upright may seem like However, this is not the full story because the a trivial task, but the neural circuitry vestibular region of the cerebellum also contains K required to perform this task is rather a high proportion of excitatory neurons called complex and not fully understood. This circuitry unipolar brush cells (UBCs). These cells, which starts with the vestibular system: a sensory sys- receive input from just a single mossy fiber, form tem in the inner ear that relies on hair cells to synapses with the granule cells (Mugnaini et al., 2011). UBCs essentially create an intermediate detect movements, and to provide our sense of step in the circuitry, where signals sent between balance and spatial awareness. The vestibular mossy fibers and granule cells can be modified. -
Spontaneous Activity Signatures of Morphologically Identified Interneurons in the Vestibulocerebellum
712 • The Journal of Neuroscience, January 12, 2011 • 31(2):712–724 Behavioral/Systems/Cognitive Spontaneous Activity Signatures of Morphologically Identified Interneurons in the Vestibulocerebellum Tom J. H. Ruigrok,1 Robert A. Hensbroek,2 and John I. Simpson2 1Department of Neuroscience, Erasmus Medical Center Rotterdam, 3000 CA Rotterdam, The Netherlands, and 2Department of Physiology and Neuroscience, New York University School of Medicine, New York, New York 10016 Cerebellar cortical interneurons such as Golgi cells, basket cells, stellate cells, unipolar brush cells, and granule cells play an essential role in the operations of the cerebellum. However, detailed functional studies of the activity of these cells in both anesthetized and behaving animals have been hampered by problems in recognizing their physiological signatures. We have extracellularly recorded the spontane- ous activity of vestibulocerebellar interneurons in ketamine/xylazine-anesthetized rats and subsequently labeled them with Neurobiotin using the juxtacellular technique. After recovery and morphological identification of these cells, they were related to statistical measures of their spontaneous activity. Golgi cells display a somewhat irregular firing pattern with relatively low average frequencies. Unipolar brush cells are characterized by more regular firing at higher rates. Basket and stellate cells are alike in their firing characteristics, which mainly stand out by their irregularity; some of them are set apart by their very slow average rate. The spontaneous activity of interneurons examined in the ketamine/xylazine rabbit fit within this general pattern. In the rabbit, granule cells were identified by the spontaneous occurrence of extremely high-frequency bursts of action potentials, which were also recognized in the rat. -
A Transcriptomic Atlas of the Mouse Cerebellum Reveals Regional Specializations and Novel Cell Types
bioRxiv preprint doi: https://doi.org/10.1101/2020.03.04.976407; this version posted March 5, 2020. 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. A transcriptomic atlas of the mouse cerebellum reveals regional specializations and novel cell types Velina Kozareva 1* , Caroline Martin1 * , Tomas Osorno2 , Stephanie Rudolph 2, Chong Guo 2, Charles Vanderburg1 , Naeem Nadaf 1, Aviv Regev1 , Wade Regehr2 , Evan Macosko1 ,3# 1 B road Institute of Harvard and MIT, Stanley Center for Psychiatric Research, 450 Main St. Cambridge, MA, USA. 2 Department of Neurobiology, Harvard Medical School, Boston, MA 02115, USA. 3 M assachusetts General Hospital, Department of Psychiatry, 55 Fruit St. Boston, MA, USA. # Correspondence: e [email protected] The cerebellum is a well-studied brain structure with diverse roles in motor learning, coordination, cognition, and autonomic regulation. Nonetheless, a complete inventory of cerebellar cell types is presently lacking. We used high-throughput transcriptional profiling to molecularly define cell types across individual lobules of the adult mouse cerebellum. Purkinje and granule neurons showed considerable regional specialization, with the greatest diversity occurring in the posterior lobules. For multiple types of cerebellar interneurons, the molecular variation within each type was more continuous, rather than discrete. For the unipolar brush cells (UBCs)— an interneuron population previously subdivided into two discrete populations— the continuous variation in gene expression was associated with a graded continuum of electrophysiological properties. -
Cerebellar Development and Neurogenesis in Zebrafish
Cerebellar Development and Neurogenesis in Zebrafish Jan Kaslin1* and Michael Brand2* 1) Australian Regenerative Medicine Institute, Monash University, Innovation Walk 15, Clayton, Victoria, 3800, Melbourne, Australia 2) Biotechnology Center and Center for Regenerative Therapies Dresden, Dresden University of Technology, Tatzberg 47, 01307, Germany *Corresponding authors: [email protected], [email protected] Keywords: zebrafish, teleost, fish, adult neurogenesis, mutant, screening, eurydendroid cell, genetic model, cerebellar development, morphogenesis, mid-hindbrain-boundary, isthmic organizer, in vivo imaging 1. Introduction Cerebellar organization and function have been studied in numerous species of fish. Fish models such as goldfish and weakly electric fish have led to important findings about the cerebellar architecture, cerebellar circuit physiology and brain evolution. owever,H most of the studied fish models are not well suited for developmental and genetic studies of the cerebellum. The rapid transparent ex utero development in zebrafish allows direct access and precise visualization of all the major events in cerebellar development. The superficial position of the cerebellarprimordium and cerebellum further facilitatesin vivo imaging of cerebellar structures and developmental events at single cell resolution. Furthermore, zebrafish is amenable to high-throughput screening techniques and forward genetics because of its fecundity and easy keeping. Forward genetics screens in zebrafish have resulted in several isolated cerebellar mutants and substantially contributed to the understanding of the genetic networks involved in hindbrain development(Bae et al. 2009;Brand et al. 1996). Recent developments in genetic tools, including the use of site specific recombinases, efficient transgenesis, inducible gene expression systems, and the targeted genome lesioning technologies TALEN and Cas9/CRISPR has opened up new avenues to manipulate and edit the genome of zebrafish (Hans et al. -
THUETT-DISSERTATION.Pdf
COMPARATIVE NEUROTOXICITY OF METHYLMERCURY AND MERCURIC CHLORIDE IN VIVO AND IN VITRO A Dissertation by KERRY ALMEDA THUETT Submitted to the Office of Graduate Studies of Texas A&M University in partial fulfillment of the requirements for the degree of DOCTOR OF PHILOSOPHY August 2009 Major Subject: Toxicology COMPARATIVE NEUROTOXICITY OF METHYLMERCURY AND MERCURIC CHLORIDE IN VIVO AND IN VITRO A Dissertation by KERRY ALMEDA THUETT Submitted to the Office of Graduate Studies of Texas A&M University in partial fulfillment of the requirements for the degree of DOCTOR OF PHILOSOPHY Approved by: Co-Chairs of Committee, Louise C. Abbott Evelyn Tiffany-Castiglioni Committee Members, Wei-Jung A. Chen Timothy D. Phillips Chair of Toxicology Faculty, Robert C. Burghardt August 2009 Major Subject: Toxicology iii ABSTRACT Comparative Neurotoxicity of Methylmercury and Mercuric Chloride In Vivo and In Vitro. (August 2009) Kerry Almeda Thuett, B.S.; M.S., Texas Tech University Co-Chairs of Advisory Committee: Dr. Louise C. Abbott Dr. Evelyn Tiffany-Castiglioni It is impossible to remove methylmercury (MeHg) from biological systems because MeHg is found throughout our environment in many fresh and salt water fish. The consumption of fish is important to human nutrition and health. The mechanism of MeHg neurotoxicity must be understood to minimize adverse exposure consequences. The dissertation objective was to: 1) compare mechanisms of MeHg neurotoxicity between animals exposed as adults and those exposed during gestation, and 2) develop an in vitro test model of in vivo MeHg exposure. Total mercury (Hg) levels in tissue / cells were determined by combustion / trapping / atomic absorption. Cell death was determined by Fluoro-Jade histochemical staining and activated caspase 3 immunohistochemistry for in vivo studies, and Trypan blue exclusion, lactate dehydrogenase activity, and cytotoxicity assays for in vitro studies.