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      The compartmental restriction of cerebellar interneurons

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          Abstract

          The Purkinje cells (PC's) of the cerebellar cortex are subdivided into multiple different molecular phenotypes that form an elaborate array of parasagittal stripes. This array serves as a scaffold around which afferent topography is organized. The ways in which cerebellar interneurons may be restricted by this scaffolding are less well-understood. This review begins with a brief survey of cerebellar topography. Next, it reviews the development of stripes in the cerebellum with a particular emphasis on the embryological origins of cerebellar interneurons. These data serve as a foundation to discuss the hypothesis that cerebellar compartment boundaries also restrict cerebellar interneurons, both excitatory [granule cells, unipolar brush cells (UBCs)] and inhibitory (e.g., Golgi cells, basket cells). Finally, it is proposed that the same PC scaffold that restricts afferent terminal fields to stripes may also act to organize cerebellar interneurons.

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          Most cited references154

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          The many faces of insulin-like peptide signalling in the brain.

          Central and peripheral insulin-like peptides (ILPs), which include insulin, insulin-like growth factor 1 (IGF1) and IGF2, exert many effects in the brain. Through their actions on brain growth and differentiation, ILPs contribute to building circuitries that subserve metabolic and behavioural adaptation to internal and external cues of energy availability. In the adult brain each ILP has distinct effects, but together their actions ultimately regulate energy homeostasis - they affect nutrient sensing and regulate neuronal plasticity to modulate adaptive behaviours involved in food seeking, including high-level cognitive operations such as spatial memory. In essence, the multifaceted activity of ILPs in the brain may be viewed as a system organization involved in the control of energy allocation.
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            Control of neuronal precursor proliferation in the cerebellum by Sonic Hedgehog.

            Cerebellar granule cells are the most abundant type of neuron in the brain, but the molecular mechanisms that control their generation are incompletely understood. We show that Sonic hedgehog (Shh), which is made by Purkinje cells, regulates the division of granule cell precursors (GCPs). Treatment of GCPs with Shh prevents differentiation and induces a potent, long-lasting proliferative response. This response can be inhibited by basic fibroblast growth factor or by activation of protein kinase A. Blocking Shh function in vivo dramatically reduces GCP proliferation. These findings provide insight into the mechanisms of normal growth and tumorigenesis in the cerebellum.
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              Sonic hedgehog regulates the growth and patterning of the cerebellum.

              The molecular bases of brain development and CNS malignancies remain poorly understood. Here we show that Sonic hedgehog (Shh) signaling controls the development of the cerebellum at multiple levels. SHH is produced by Purkinje neurons, it is required for the proliferation of granule neuron precursors and it induces the differentiation of Bergmann glia. Blocking SHH function in vivo results in deficient granule neuron and Bergmann glia differentiation as well as in abnormal Purkinje neuron development. Thus, our findings provide a molecular model for the growth and patterning of the cerebellum by SHH through the coordination of the development of cortical cerebellar cell types. In addition, they provide a cellular context for medulloblastomas, childhood cancers of the cerebellum.
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                Author and article information

                Journal
                Front Neural Circuits
                Front Neural Circuits
                Front. Neural Circuits
                Frontiers in Neural Circuits
                Frontiers Media S.A.
                1662-5110
                22 January 2013
                2012
                : 6
                : 123
                Affiliations
                [1] 1Division of Neuroscience, San Raffaele Scientific Institute Milan, Italy
                [2] 2Department of Cell Biology and Anatomy, Genes and Development Research Group, Faculty of Medicine, Hotchkiss Brain Institute, The University of Calgary Calgary, AB, Canada
                Author notes

                Edited by: Egidio D‘Angelo, University of Pavia, Italy

                Reviewed by: Leonard Maler, University of Ottawa, Canada; Samuel S. Wang, Princeton University, USA

                *Correspondence: Richard Hawkes, Department of Cell Biology and Anatomy, Genes and Development Research Group, Faculty of Medicine, Hotchkiss Brain Institute, University of Calgary, 3330 Hospital Drive N.W., Calgary, AB T2N 4N1, Canada. e-mail: rhawkes@ 123456ucalgary.ca
                Article
                10.3389/fncir.2012.00123
                3551280
                23346049
                ed55d7c1-26e9-4b3f-996d-192decc05222
                Copyright © 2013 Consalez and Hawkes.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in other forums, provided the original authors and source are credited and subject to any copyright notices concerning any third-party graphics etc.

                History
                : 21 September 2012
                : 26 December 2012
                Page count
                Figures: 6, Tables: 0, Equations: 0, References: 195, Pages: 14, Words: 12873
                Categories
                Neuroscience
                Review Article

                Neurosciences
                purkinje cell,stripe,zone,golgi cell,basket cell,stellate cell,unipolar brush cell,granule cell
                Neurosciences
                purkinje cell, stripe, zone, golgi cell, basket cell, stellate cell, unipolar brush cell, granule cell

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