bims-climfi Biomed News
on Cerebellar cortical circuitry
Issue of 2021–02–07
two papers selected by
Jun Maruta, Mount Sinai Health System
  1. Origins, Development, and Compartmentation of the Granule Cells of the Cerebellum.
  2. Glial amplification of synaptic signals.
  1. Front Neural Circuits. 2020 ;14 611841
    Origins, Development, and Compartmentation of the Granule Cells of the Cerebellum.
    G Giacomo Consalez, Daniel Goldowitz, Filippo Casoni, Richard Hawkes.
      Granule cells (GCs) are the most numerous cell type in the cerebellum and indeed, in the brain: at least 99% of all cerebellar neurons are granule cells. In this review article, we first consider the formation of the upper rhombic lip, from which all granule cell precursors arise, and the way by which the upper rhombic lip generates the external granular layer, a secondary germinal epithelium that serves to amplify the upper rhombic lip precursors. Next, we review the mechanisms by which postmitotic granule cells are generated in the external granular layer and migrate radially to settle in the granular layer. In addition, we review the evidence that far from being a homogeneous population, granule cells come in multiple phenotypes with distinct topographical distributions and consider ways in which the heterogeneity of granule cells might arise during development.
    Keywords:  Bergmann glial fibers; cerebellum; compartmentation; external granular layer; granule cell; radial migration; upper rhombic lip
    DOI:  https://doi.org/10.3389/fncir.2020.611841
  2. J Physiol. 2021 Feb 02.
    Glial amplification of synaptic signals.
    Kaoru Beppu, Naoko Kubo, Ko Matsui.
       KEY POINTS: Recent studies have repeatedly demonstrated the cross talk of heterogeneous signals between neuronal and glial circuits. Here, we investigated the mechanism and the influence of physiological interactions between neurons and glia in the cerebellum. We found that the cerebellar astrocytes, Bergmann glial cells, react to exogenously applied glutamate, glutamate transporter substrate (D-Aspartate), and synaptically released glutamate. In response, the Bergmann glial cells release glutamate through volume-regulated anion channels. It is generally assumed that all of postsynaptic current is mediated by presynaptically released glutamate. But we showed that a part of postsynaptic current is mediated by glutamate released from Bergmann glial cells. Optogenetic manipulation of Bergmann glial state with archaerhodpsin-T or channelrhodopsin-2 reduced or augmented the amount of glial glutamate release, respectively. Our data indicates that glutamate-induced glutamate release in Bergmann glia serve as an effective amplifier of excitatory information processing in the brain.
    ABSTRACT: Transmitter released from presynaptic neurons has been considered to be the sole generator of postsynaptic excitatory signals. However, astrocytes of the glial cell population have also been shown to release transmitter that can react on postsynaptic receptors. Therefore, we investigated whether astrocytes take part in generation of at least a part of the synaptic current. In this study, mice cerebellar acute slices were prepared and whole cell patch clamp recordings were performed. We found that the Bergmann glial cells (BGs), a type of astrocyte in the cerebellum, reacts to a glutamate transporter substrate, D-Aspartate (D-Asp) and an anion conductance is generated and glutamate is released from the BGs. The glutamate release was attenuated or augmented by modulating the state of BGs with activation of light-sensitive proteins, archaerhodopsin-T (ArchT) or channelrhodopsin-2 (ChR2) expressed on BGs, respectively. Glutamate release appears to be mediated by anion channels that can be blocked by volume-regulated anion channel (VRAC) specific blocker. Synaptic response to a train of parallel fiber (PF) stimulation was recorded from Purkinje cells (PCs). The latter part of the response was also attenuated or augmented by glial modulation with ArchT or ChR2, respectively. Thus, BGs effectively function as an excitatory signal amplifier and a part of the 'synaptic' current is actually mediated by glutamate released from BGs. These data show that the state of BGs have a potential for having direct and fundamental consequences on the functioning of information processing in the brain. This article is protected by copyright. All rights reserved.
    Keywords:  astrocyte; gliotransmission; glutamate; optogenetics; synaptic transmission
    DOI:  https://doi.org/10.1113/JP280857
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