GAD67-mediated GABA Synthesis and Signaling Impinges on Directing Basket Cell Axonal Projections Toward Purkinje Cells in the Cerebellum

2021 ◽  
Author(s):  
Hideki Miwa ◽  
Ken Kobayashi ◽  
Shinobu Hirai ◽  
Mitsuhiko Yamada ◽  
Masahiko Watanabe ◽  
...  
Keyword(s):  
Purkinje Cells ◽  
Basket Cell ◽  
Axonal Projections ◽  
Gaba Synthesis

Roles of GABA Signaling in Directing Basket Cell Axonal Projections Toward Purkinje Cells in the Cerebellum

2020 ◽  
Author(s):  
Hideki Miwa ◽  
Ken Kobayashi ◽  
Shinobu Hirai ◽  
Mitsuhiko Yamada ◽  
Masahiko Watanabe ◽  
...  
Keyword(s):  
Purkinje Cells ◽  
Motor Coordination ◽  
Basket Cell ◽  
K Channel ◽  
Mouse Strains ◽  
Gamma Aminobutyric Acid ◽  
Knock Out ◽  
Inhibitory Neurotransmitter ◽  
Basket Cells ◽  
Gaba Signaling

Abstract Gamma-aminobutyric acid (GABA) is a major inhibitory neurotransmitter in the central nervous system, synthesized by two isoforms of glutamate decarboxylase (GAD): GAD65 and GAD67. GABA may act as a trophic factor during brain development, but its contribution to the development and maturation of cerebellar neural circuits is not known. To understand the roles of GABA in cerebellar development and associated functions in motor coordination and balance, we examined GAD65 conventional knock out (KO) mice and mice in which GAD67 was eliminated in parvalbumin-expressing neurons ( PV-Cre ; GAD67 flox/flox mice). We found aberrant subcellular localization of the Shaker-type K channel Kv1.1 in basket cell collaterals of PV-Cre ; GAD67 flox/flox mice and abnormal projections from basket cells to Purkinje cells in both mouse strains. Furthermore, PV-Cre ; GAD67 flox/flox mice exhibited abnormal motor coordination in the rotarod test. These results indicate that GABA signaling in the cerebellum during development is critical for establishing appropriate connections between basket cells and Purkinje cells and is associated with motor coordination in mice.

Developmental switching of perisomatic innervation from climbing fibers to basket cell fibers in developing cerebellar purkinje cells

2011 ◽  
Vol 71 ◽  
pp. e215
Author(s):  
Ryoichi Ichikawa ◽  
Miwako Yamasaki ◽  
Taisuke Miyazaki ◽  
Haruyuki Tatsumi ◽  
Masahiko Watanabe
Keyword(s):  
Purkinje Cells ◽  
Climbing Fibers ◽  
Basket Cell ◽  
Cerebellar Purkinje Cells

scholarly journals Purkinje cell neurotransmission patterns cerebellar basket cells into zonal modules that are defined by distinct pinceau sizes

2020 ◽  
Author(s):  
Joy Zhou ◽  
Amanda M. Brown ◽  
Elizabeth P. Lackey ◽  
Marife Arancillo ◽  
Tao Lin ◽  
...  
Keyword(s):  
Purkinje Cell ◽  
Purkinje Cells ◽  
Initial Segment ◽  
Molecular Diversity ◽  
Basket Cell ◽  
Basket Cells ◽  
Conditional Allele ◽  
Functional Zones ◽  
Cell Somata ◽  
Ramón Y Cajal

AbstractRamón y Cajal proclaimed the neuron doctrine based on circuit features he exemplified using cerebellar basket cell projections. Basket cells form dense inhibitory plexuses that wrap Purkinje cell somata and terminate as pinceaux at the initial segment of axons. Here, we demonstrate that HCN1, Kv1.1, PSD95 and GAD67 unexpectedly mark patterns of basket cell pinceaux that map onto Purkinje cell functional zones. Using cell-specific genetic tracing with an Ascl1CreERT2 mouse conditional allele, we reveal that basket cell zones comprise different sizes of pinceaux. We tested whether Purkinje cells instruct the assembly of inhibitory projections into zones, as they do for excitatory afferents. Genetically silencing Purkinje cell neurotransmission blocks the formation of sharp Purkinje cell zones and disrupts excitatory axon patterning. The distribution of pinceaux into size-specific zones is eliminated without Purkinje cell output. Our data uncover the cellular and molecular diversity of a foundational synapse that revolutionized neuroscience.

scholarly journals Purkinje cell neurotransmission patterns cerebellar basket cells into zonal modules defined by distinct pinceau sizes

eLife ◽  
2020 ◽  
Vol 9 ◽  
Author(s):  
Joy Zhou ◽  
Amanda M Brown ◽  
Elizabeth P Lackey ◽  
Marife Arancillo ◽  
Tao Lin ◽  
...  
Keyword(s):  
Purkinje Cell ◽  
Purkinje Cells ◽  
Initial Segment ◽  
Molecular Diversity ◽  
Basket Cell ◽  
Basket Cells ◽  
Conditional Allele ◽  
Functional Zones ◽  
Cell Somata ◽  
Ramón Y Cajal

Ramón y Cajal proclaimed the neuron doctrine based on circuit features he exemplified using cerebellar basket cell projections. Basket cells form dense inhibitory plexuses that wrap Purkinje cell somata and terminate as pinceaux at the initial segment of axons. Here, we demonstrate that HCN1, Kv1.1, PSD95 and GAD67 unexpectedly mark patterns of basket cell pinceaux that map onto Purkinje cell functional zones. Using cell-specific genetic tracing with an Ascl1CreERT2 mouse conditional allele, we reveal that basket cell zones comprise different sizes of pinceaux. We tested whether Purkinje cells instruct the assembly of inhibitory projections into zones, as they do for excitatory afferents. Genetically silencing Purkinje cell neurotransmission blocks the formation of sharp Purkinje cell zones and disrupts excitatory axon patterning. The distribution of pinceaux into size-specific zones is eliminated without Purkinje cell GABAergic output. Our data uncover the cellular and molecular diversity of a foundational synapse that revolutionized neuroscience.

scholarly journals Developmental Switching of Perisomatic Innervation from Climbing Fibers to Basket Cell Fibers in Cerebellar Purkinje Cells

2011 ◽  
Vol 31 (47) ◽  
pp. 16916-16927 ◽  
Author(s):  
R. Ichikawa ◽  
M. Yamasaki ◽  
T. Miyazaki ◽  
K. Konno ◽  
K. Hashimoto ◽  
...  
Keyword(s):  
Purkinje Cells ◽  
Climbing Fibers ◽  
Basket Cell ◽  
Cerebellar Purkinje Cells

Ultrastorcture of Cerebellar Purkinje Cells in Rats Subjected To Partial Global Cerebral Ischemia

1985 ◽  
Vol 43 ◽  
pp. 674-675
Author(s):  
R.V.W. Dimlich ◽  
M.H. Biros
Keyword(s):  
Cerebral Ischemia ◽  
Purkinje Cells ◽  
Cell Types ◽  
Microscopic Level ◽  
Global Cerebral Ischemia ◽  
Light Microscopic Level ◽  
Cerebellar Damage ◽  
Cerebellar Injury ◽  
Cerebellar Purkinje Cells ◽  
Cell Changes

In severe cerebral ischemia, Purkinje cells of the cerebellum are one of the cell types most vulnerable to anoxic damage. In the partial (forebrain) global ischemic (PGI) model of the rat, Paljärvi noted at the light microscopic level that cerebellar damage is inconsistant and when present, milder than in the telencephalon, diencephalon and rostral brain stem. Cerebellar injury was observed in 3 of 4 PGI rats following 5 minutes of reperfusion but in none of the rats after 90 min of reperfusion. To evaluate a time between these two extremes (5 and 90 min), the present investigation used the PGI model to study the effects of ischemia on the ultrastructure of cerebellar Purkinje cells in rats that were sacrificed after 30 min of reperfusion. This time also was chosen because lactic acid that is thought to contribute to ischemic cell changes in PGI is at a maximum after 30 min of reperfusion.

Ultrasturcture of cerebellar cells and neuropil in rats subjected to partial global cerebral ischemia

1986 ◽  
Vol 44 ◽  
pp. 126-127
Author(s):  
R.V.W. Dimlich ◽  
M.H. Biros
Keyword(s):  
Purkinje Cells ◽  
Glial Cells ◽  
Granule Cells ◽  
Molecular Layer ◽  
Cell Types ◽  
Primary Objective ◽  
Global Cerebral Ischemia ◽  
Forebrain Ischemia ◽  
Substantial Evidence ◽  
Cerebellar Cells

Although a previous study in this laboratory determined that Purkinje cells of the rat cerebellum did not appear to be damaged following 30 min of forebrain ischemia followed by 30 min of reperfusion, it was suggested that an increase in rough endoplasmic reticulum (RER) and/or polysomes had occurred in these cells. The primary objective of the present study was to morphometrically determine whether or not this increase had occurred. In addition, since there is substantial evidence that glial cells may be affected by ischemia earlier than other cell types, glial cells also were examined. To ascertain possible effects on other cerebellar components, granule cells and neuropil near Purkinje cells as well as neuropil in the molecular layer also were evaluated in this investigation.

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