Bidirectional Parallel Fiber Plasticity in the Cerebellum under Climbing Fiber Control

Coesmans, Michiel; Weber, John T.; Zeeuw, Chris I. De; Hansel, Christian

doi:10.1016/j.neuron.2004.10.031

Cited by 398 publications

(513 citation statements)

References 69 publications

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“…In contrast to observations at the cerebellar level by Coesmans et al (16), a high calcium threshold for LTP and a low calcium threshold for LTD induction have been demonstrated at the hippocampal level (37,38). A LTP induction protocol applied to hippocampal pyramidal cells would thus lead to a LTD if calcium entry were reduced.…”

Section: Discussionmentioning

confidence: 62%

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Purkinje cell dysfunction and alteration of long-term synaptic plasticity in fetal alcohol syndrome

Servais

Hourez²,

Bearzatto³

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

100

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In cerebellum and other brain regions, neuronal cell death because of ethanol consumption by the mother is thought to be the leading cause of neurological deficits in the offspring. However, little is known about how surviving cells function. We studied cerebellar Purkinje cells in vivo and in vitro to determine whether function of these cells was altered after prenatal ethanol exposure. We observed that Purkinje cells that were prenatally exposed to ethanol presented decreased voltage-gated calcium currents because of a decreased expression of the ␥-isoform of protein kinase C. Longterm depression at the parallel fiber-Purkinje cell synapse in the cerebellum was converted into long-term potentiation. This likely explains the dramatic increase in Purkinje cell firing and the rapid oscillations of local field potential observed in alert fetal alcohol syndrome mice. Our data strongly suggest that reversal of longterm synaptic plasticity and increased firing rates of Purkinje cells in vivo are major contributors to the ataxia and motor learning deficits observed in fetal alcohol syndrome. Our results show that calcium-related neuronal dysfunction is central to the pathogenesis of the neurological manifestations of fetal alcohol syndrome and suggest new methods for treatment of this disorder.calcium ͉ cerebellum ͉ protein kinase ͉ long-term depression ͉ motor learning F etal alcohol syndrome (FAS) is the leading cause of intellectual disability in the Western world with a prevalence of 1 to 1.5 cases per 1,000 live births (1) and a lifetime cost of care of approximately $1.4 million per case. This cost is mainly because of ethanol toxicity in the developing central nervous system, causing intellectual disability, deficits in learning, and fine-motor dysfunction (2).The cerebellum is one of the main targets of in utero ethanol toxicity (3). Within the cerebellum, Purkinje cells (PCs) are highly sensitive to ethanol. PCs constitute the sole output of the cerebellar cortex and thus have a central functional role in integration. All animal models of FAS display a reduction in the number of PCs by Ϸ20% (4), and various authors have proposed that neuronal loss is the only cause of cerebellar deficits in FAS. One study conducted on adult anesthetized rats with FAS led to the conclusion that PCs that survive ethanol administration function normally (5). Thomas et al. (6) found a correlation between total PCs number and motor performance. These experimental data led to the assumption that surviving PCs function normally and that motor coordination impairment in FAS results only from a quantitative defect of PCs. This is crucially important from a therapeutic point of view because very few options exist to replace dead neurons. Many studies have therefore focused on different ways to decrease PC loss in FAS (7,8). However, different models of ataxia that result from PC death per se (pcd mice, SV4 mice, T147 transgenic mice) have demonstrated that considerable neuropathology can occur without the manifestation of a neurologic...

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Section: Discussionmentioning

confidence: 62%

“…Intracytoplasmic Ca 2ϩ concentration controls the direction of long term synaptic plasticity at the parallel fiber-PC synapse (16). Indeed, concomitant stimulation of parallel and climbing fibers leads to a parallel fiber-PC LTD under standard conditions and LTP when calcium buffering lowers intracytoplasmic Ca 2ϩ concentration.…”

Section: Discussionmentioning

confidence: 99%

Purkinje cell dysfunction and alteration of long-term synaptic plasticity in fetal alcohol syndrome

Servais

Hourez²,

Bearzatto³

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

100

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“…On the other hand, TG6 was expressed throughout the deep cerebellar nuclei which receive input from Purkinje cells and send output information to other brain regions. In addition, numerous TG6-positive neurons were contained in the pontine nucleus and vestibular nucleus, which send many mossy fiber axons to the cerebellum (Coesmans et al, 2004). The inferior olivary nucleus, which sends climbing fibers to the cerebellum (Devor, 2000), also contained TG6-positve neurons.…”

Section: Discussionmentioning

confidence: 99%

Distribution of Transglutaminase 6 in the Central Nervous System of Adult Mice

Liu

Tang

Lan

et al. 2013

The Anatomical Record

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Our previous study identified a new form of spinocerebellar ataxia (SCA), in which mutations in the gene coding for transglutaminase 6 (TG6) were suggested to be causative. However, the data concerning cellular distribution of TG6 in the brain is still fragmentary. Therefore, we now report a comprehensive immunohistochemical examination of the expression profile of TG6 in adult mouse brain. TG6 was abundantly expressed in the septal region, basal ganglia, hypothalamus and brainstem. Notably, numerous TG6-positive neurons were found in the key brain regions involved in regulating locomotion activity, including the globus pallidus, subthalamic nucleus, substantia nigra, cerebellum, some precerebellar nuclei, and spinal motor neurons. Double immunostaining showed that the vast majority of TG6-positive neurons in the reticular nigra were GABAergic and those in the compact nigra were not dopaminergic. In addition, double staining for TG6 with either anti-NeuN or glial fibrillary acidic protein (GFAP) antibodies demonstrated exclusive NeuN-TG6 co-localization. This study presents a comprehensive overview of TG6 expression in the mouse brain, and provides insight for investigating the role of TG6 in the development of SCA. Anat Rec, 296:1576Rec, 296: -1587Rec, 296: , 2013. V C 2013 Wiley Periodicals, Inc.Key words: spinocerebellar ataxia; transglutaminase 6; immunohistochemistry; brain; distribution Abbreviations used: CNS 5 central nervous system; GABA 5 gammaaminobutyric acid; GAD67 5 glutamate acid decarboxylase 67; GFAP 5 glial fibrillary acidic protein; GFP 5 green fluorescent protein; NeuN 5 neuron specific nuclear protein; SCA 5 spinocerebellar ataxia; TGM 5 transglutaminase; TH 5 tyrosine hydroxylase.

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“…In this case, high postsynaptic Ca 2C levels are required that presumably result from the activation of P/Q calcium channels after the strong depolarization ensuing climbing fiber activity and from release from intracellular Ca 2C stores. 78 Therefore, as briefly presented here and illustrated in the articles listed in Table 1, T-type channels participate to numerous synaptic plasticity mechanisms, both homo and heterosynaptic, involving different partners and both pre-and post-synaptic modifications (the main pathways underlying T-channel dependent plasticity at both excitatory and inhibitory synapses are schematically presented in Fig. 5).…”

Section: T-type Channels: Partner Of Diverse Long-term Synaptic Plastmentioning

confidence: 96%

T-type calcium channels in synaptic plasticity

Leresche

Lambert

2016

Channels

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The role of T-type calcium currents is rarely considered in the extensive literature covering the mechanisms of long-term synaptic plasticity. This situation reflects the lack of suitable T-type channel antagonists that till recently has hampered investigations of the functional roles of these channels. However, with the development of new pharmacological and genetic tools, a clear involvement of T-type channels in synaptic plasticity is starting to emerge. Here, we review a number of studies showing that T-type channels participate to numerous homo-and heterosynaptic plasticity mechanisms that involve different molecular partners and both pre-and postsynaptic modifications. The existence of T-channel dependent and independent plasticity at the same synapse strongly suggests a subcellular localization of these channels and their partners that allows specific interactions. Moreover, we illustrate the functional importance of T-channel dependent synaptic plasticity in neocortex and thalamus.

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Bidirectional Parallel Fiber Plasticity in the Cerebellum under Climbing Fiber Control

Cited by 398 publications

References 69 publications

Purkinje cell dysfunction and alteration of long-term synaptic plasticity in fetal alcohol syndrome

Purkinje cell dysfunction and alteration of long-term synaptic plasticity in fetal alcohol syndrome

Distribution of Transglutaminase 6 in the Central Nervous System of Adult Mice

T-type calcium channels in synaptic plasticity

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