scholarly journals Modulatory Effects of Monoamines and Perineuronal Nets on Output of Cerebellar Purkinje Cells

2021 ◽  
Vol 15 ◽  
Author(s):  
Moritoshi Hirono ◽  
Fuyuki Karube ◽  
Yuchio Yanagawa
Keyword(s):  
Purkinje Cells ◽  
Motor Coordination ◽  
Gaba Release ◽  
Cerebellar Nuclei ◽  
Brain Regions ◽  
Perineuronal Nets ◽  
Gabaergic Transmission ◽  
Neural Connections ◽  
Brain Functions ◽  
Cerebellar Purkinje Cells

Classically, the cerebellum has been thought to play a significant role in motor coordination. However, a growing body of evidence for novel neural connections between the cerebellum and various brain regions indicates that the cerebellum also contributes to other brain functions implicated in reward, language, and social behavior. Cerebellar Purkinje cells (PCs) make inhibitory GABAergic synapses with their target neurons: other PCs and Lugaro/globular cells via PC axon collaterals, and neurons in the deep cerebellar nuclei (DCN) via PC primary axons. PC-Lugaro/globular cell connections form a cerebellar cortical microcircuit, which is driven by serotonin and noradrenaline. PCs’ primary outputs control not only firing but also synaptic plasticity of DCN neurons following the integration of excitatory and inhibitory inputs in the cerebellar cortex. Thus, strong PC-mediated inhibition is involved in cerebellar functions as a key regulator of cerebellar neural networks. In this review, we focus on physiological characteristics of GABAergic transmission from PCs. First, we introduce monoaminergic modulation of GABAergic transmission at synapses of PC-Lugaro/globular cell as well as PC-large glutamatergic DCN neuron, and a Lugaro/globular cell-incorporated microcircuit. Second, we review the physiological roles of perineuronal nets (PNNs), which are organized components of the extracellular matrix and enwrap the cell bodies and proximal processes, in GABA release from PCs to large glutamatergic DCN neurons and in cerebellar motor learning. Recent evidence suggests that alterations in PNN density in the DCN can regulate cerebellar functions.

scholarly journals Disrupted Calcium Signaling in Animal Models of Human Spinocerebellar Ataxia (SCA)

2019 ◽  
Vol 21 (1) ◽  
pp. 216 ◽  
Author(s):  
Francesca Prestori ◽  
Francesco Moccia ◽  
Egidio D’Angelo
Keyword(s):  
Animal Models ◽  
Purkinje Cell ◽  
Calcium Signaling ◽  
Purkinje Cells ◽  
Motor Coordination ◽  
Cerebellar Atrophy ◽  
Cerebellar Nuclei ◽  
Spinocerebellar Ataxias ◽  
Cell Degeneration ◽  
Cerebellar Purkinje Cells

Spinocerebellar ataxias (SCAs) constitute a heterogeneous group of more than 40 autosomal-dominant genetic and neurodegenerative diseases characterized by loss of balance and motor coordination due to dysfunction of the cerebellum and its efferent connections. Despite a well-described clinical and pathological phenotype, the molecular and cellular events that underlie neurodegeneration are still poorly undaerstood. Emerging research suggests that mutations in SCA genes cause disruptions in multiple cellular pathways but the characteristic SCA pathogenesis does not begin until calcium signaling pathways are disrupted in cerebellar Purkinje cells. Ca2+ signaling in Purkinje cells is important for normal cellular function as these neurons express a variety of Ca2+ channels, Ca2+-dependent kinases and phosphatases, and Ca2+-binding proteins to tightly maintain Ca2+ homeostasis and regulate physiological Ca2+-dependent processes. Abnormal Ca2+ levels can activate toxic cascades leading to characteristic death of Purkinje cells, cerebellar atrophy, and ataxia that occur in many SCAs. The output of the cerebellar cortex is conveyed to the deep cerebellar nuclei (DCN) by Purkinje cells via inhibitory signals; thus, Purkinje cell dysfunction or degeneration would partially or completely impair the cerebellar output in SCAs. In the absence of the inhibitory signal emanating from Purkinje cells, DCN will become more excitable, thereby affecting the motor areas receiving DCN input and resulting in uncoordinated movements. An outstanding advantage in studying the pathogenesis of SCAs is represented by the availability of a large number of animal models which mimic the phenotype observed in humans. By mainly focusing on mouse models displaying mutations or deletions in genes which encode for Ca2+ signaling-related proteins, in this review we will discuss the several pathogenic mechanisms related to deranged Ca2+ homeostasis that leads to significant Purkinje cell degeneration and dysfunction.

scholarly journals Sex in the brain: hormones and sex differences

2016 ◽  
Vol 18 (4) ◽  
pp. 373-383 ◽  
Keyword(s):  
Sex Differences ◽  
Sex Hormones ◽  
Genetic Factors ◽  
Motor Coordination ◽  
Brain Regions ◽  
New Era ◽  
Brain Functions ◽  
Opioid Sensitivity ◽  
Males And Females ◽  
The Brain

Contrary to popular belief, sex hormones act throughout the entire brain of both males and females via both genomic and nongenomic receptors. Many neural and behavioral functions are affected by estrogens, including mood, cognitive function, blood pressure regulation, motor coordination, pain, and opioid sensitivity. Subtle sex differences exist for many of these functions that are developmentally programmed by hormones and by not yet precisely defined genetic factors, including the mitochondrial genome. These sex differences, and responses to sex hormones in brain regions and upon functions not previously regarded as subject to such differences, indicate that we are entering a new era in our ability to understand and appreciate the diversity of gender-related behaviors and brain functions.

scholarly journals Impaired motor coordination and persistent multiple climbing fiber innervation of cerebellar Purkinje cells in mice lacking G q

1997 ◽  
Vol 94 (25) ◽  
pp. 14089-14094 ◽  
Author(s):  
S. Offermanns ◽  
K. Hashimoto ◽  
M. Watanabe ◽  
W. Sun ◽  
H. Kurihara ◽  
...  
Keyword(s):  
Purkinje Cells ◽  
Motor Coordination ◽  
Climbing Fiber ◽  
Cerebellar Purkinje Cells

scholarly journals Optogenetic Control of Motor Coordination by Gi/o Protein-coupled Vertebrate Rhodopsin in Cerebellar Purkinje Cells

2011 ◽  
Vol 286 (29) ◽  
pp. 25848-25858 ◽  
Author(s):  
Davina V. Gutierrez ◽  
Melanie D. Mark ◽  
Olivia Masseck ◽  
Takashi Maejima ◽  
Denise Kuckelsberg ◽  
...  
Keyword(s):  
Purkinje Cells ◽  
Motor Coordination ◽  
Cerebellar Purkinje Cells ◽  
Optogenetic Control

scholarly journals Calbindin in Cerebellar Purkinje Cells Is a Critical Determinant of the Precision of Motor Coordination

2003 ◽  
Vol 23 (8) ◽  
pp. 3469-3477 ◽  
Author(s):  
Jaroslaw J. Barski ◽  
Jana Hartmann ◽  
Christine R. Rose ◽  
Freek Hoebeek ◽  
Karin Mörl ◽  
...  
Keyword(s):  
Purkinje Cells ◽  
Motor Coordination ◽  
Critical Determinant ◽  
Cerebellar Purkinje Cells

scholarly journals Genetic recovery of ErbB4 in adulthood partially restores brain functions in null mice

2018 ◽  
Vol 115 (51) ◽  
pp. 13105-13110 ◽  
Author(s):  
Hongsheng Wang ◽  
Fang Liu ◽  
Wenbing Chen ◽  
Xiangdong Sun ◽  
Wanpeng Cui ◽  
...  
Keyword(s):  
Neural Development ◽  
Critical Role ◽  
Gaba Release ◽  
Brain Disorders ◽  
Gabaergic Transmission ◽  
Brain Functions ◽  
Adult Mice ◽  
Mutant Strains ◽  
And Behavior

Neurotrophic factor NRG1 and its receptor ErbB4 play a role in GABAergic circuit assembly during development. ErbB4 null mice possess fewer interneurons, have decreased GABA release, and show impaired behavior in various paradigms. In addition, NRG1 and ErbB4 have also been implicated in regulating GABAergic transmission and plasticity in matured brains. However, current ErbB4 mutant strains are unable to determine whether phenotypes in adult mutant mice result from abnormal neural development. This important question, a glaring gap in understanding NRG1–ErbB4 function, was addressed by using two strains of mice with temporal control of ErbB4 deletion and expression, respectively. We found that ErbB4 deletion in adult mice impaired behavior and GABA release but had no effect on neuron numbers and morphology. On the other hand, some deficits due to the ErbB4 null mutation during development were alleviated by restoring ErbB4 expression at the adult stage. Together, our results indicate a critical role of NRG1–ErbB4 signaling in GABAergic transmission and behavior in adulthood and suggest that restoring NRG1–ErbB4 signaling at the postdevelopmental stage might benefit relevant brain disorders.

scholarly journals Numb deficiency in cerebellar Purkinje cells impairs synaptic expression of metabotropic glutamate receptor and motor coordination

2015 ◽  
Vol 112 (50) ◽  
pp. 15474-15479 ◽  
Author(s):  
Liang Zhou ◽  
Dong Yang ◽  
De-Juan Wang ◽  
Ya-Jun Xie ◽  
Jia-Huan Zhou ◽  
...  
Keyword(s):  
Cell Fate ◽  
Purkinje Cells ◽  
Glutamate Receptor ◽  
Motor Coordination ◽  
Metabotropic Glutamate Receptor ◽  
Constitutive Expression ◽  
Metabotropic Glutamate ◽  
Associated Proteins ◽  
Cerebellar Purkinje Cells

Protein Numb, first identified as a cell-fate determinant in Drosophila, has been shown to promote the development of neurites in mammals and to be cotransported with endocytic receptors in clathrin-coated vesicles in vitro. Nevertheless, its function in mature neurons has not yet been elucidated. Here we show that cerebellar Purkinje cells (PCs) express high levels of Numb during adulthood and that conditional deletion of Numb in PCs is sufficient to impair motor coordination despite maintenance of a normal cerebellar cyto-architecture. Numb proved to be critical for internalization and recycling of metabotropic glutamate 1 receptor (mGlu1) in PCs. A significant decrease of mGlu1 and an inhibition of long-term depression at the parallel fiber–PC synapse were observed in conditional Numb knockout mice. Indeed, the trafficking of mGlu1 induced by agonists was inhibited significantly in these mutants, but the expression of ionotropic glutamate receptor subunits and of mGlu1-associated proteins was not affected by the loss of Numb. Moreover, transient and persistent forms of mGlu1 plasticity were robustly induced in mutant PCs, suggesting that they do not require mGlu1 trafficking. Together, our data demonstrate that Numb is a regulator for constitutive expression and dynamic transport of mGlu1.

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