The expression of cerebellar LTD in culture is not associated with changes in AMPA-receptor kinetics, agonist affinity, or unitary conductance

Linden, David J.

doi:10.1073/pnas.241384598

Cited by 57 publications

(36 citation statements)

References 28 publications

(33 reference statements)

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“…Genetic elimination of either ␣CaMKII (26) or ␤CaMKII (59) results in deficits in locomotor performance and/or learning and, analogous to the situation seen for pep-19-null mice, PF-PC LTD is converted into LTP. Because Pep-19 is highly enriched in PC and not present in granular neurons, it is clear that this change in the direction of synaptic plasticity is due to postsynaptic mechanisms that most likely involve insertion or internalization of AMPA (␣-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid) receptor subunits (11,38,40,46,61). It has been proposed that the direction of synaptic plasticity at PF-PC synapses is governed by the balance between postsynaptic protein kinases and phosphatases, where kinases are responsible for LTD and phosphatases are responsible for LTP mechanisms (4,12,32,49).…”

Section: Discussionmentioning

confidence: 99%

Impaired Locomotor Learning and Altered Cerebellar Synaptic Plasticity in pep-19/pcp4-Null Mice

Peng

Blundon

Rong

et al. 2011

Molecular and Cellular Biology

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Section: Discussionmentioning

confidence: 99%

Impaired Locomotor Learning and Altered Cerebellar Synaptic Plasticity in pep-19/pcp4-Null Mice

Peng

Blundon

Rong

et al. 2011

Molecular and Cellular Biology

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“…In PCs, LTD is expressed postsynaptically as an attenuation of the current mediated by AMPAR channels, caused by a decrease in the number of synaptic AMPARs (Linden, 2001). Therefore, the synaptic depression was simulated as a reduction in the number of synaptic AMPARs, implemented according to the mechanisms of AM-PAR trafficking (Fig.…”

Section: Camentioning

confidence: 99%

“…Cerebellar LTD is a robust and persistent decrease in the synaptic transmission between parallel fibers (PFs) and Purkinje cells (PCs), expressed as a reduction in the number of synaptic AMPA receptors (AMPARs) (Matsuda et al, 2000;Linden, 2001;Steinberg et al, 2004). It is induced experimentally by protocols that promote transitory rises in the postsynaptic intracellular calcium ions concentration ([Ca 2ϩ ]) (Konnerth et al, 1992).…”

Section: Introductionmentioning

confidence: 99%

A Stochastic Signaling Network Mediates the Probabilistic Induction of Cerebellar Long-Term Depression

Antunes

Schutter²

2012

Journal of Neuroscience

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Many cellular processes involve a small number of molecules and undergo stochastic fluctuations in their levels of activity. Cerebellar long-term depression (LTD) is a form of synaptic plasticity expressed as a reduction in the number of synaptic AMPA receptors (AMPARs) in Purkinje cells. We developed a stochastic model of the LTD signaling network, including a PKC-ERK-cPLA 2 positive feedback loop and mechanisms of AMPAR trafficking, and tuned the model to replicate calcium uncaging experiments. The signaling network activity in single synapses switches between two discrete stable states (LTD and non-LTD) in a probabilistic manner. The stochasticity of the signaling network causes threshold dithering and allows at the macroscopic level for many different and stable mean magnitudes of depression. The probability of LTD occurrence in a single spine is only modulated by the concentration and duration of the signal used to trigger it, and inputs with the same magnitude can give rise to two different responses; there is no threshold for the input signal. The stochasticity is intrinsic to the signaling network and not mostly dependent on noise in the calcium input signal, as has been suggested previously. The activities of the ultrasensitive ERK and of cPLA 2 undergo strong stochastic fluctuations. Conversely, PKC, which acts as a noise filter, is more constantly activated. Systematic variation of the biochemical population size demonstrates that threshold dithering and the absence of spontaneous LTD depend critically on the number of molecules in a spine, indicating constraints on spine size in Purkinje cells.

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“…Dynamic regulation of the receptor number is primarily responsible for expression of long-term synaptic plasticity (Linden, 2001;Lei et al, 2003). It is also suggested that differences in the number of postsynaptic receptors contribute to the spatial scaling of excitatory inputs depending on the location of synapses in hippocampal pyramidal cells (Smith et al, 2003).…”

Section: Introductionmentioning

confidence: 99%

Number and Density of AMPA Receptors in Single Synapses in Immature Cerebellum

Tanaka¹,

Matsuzaki²,

Tarusawa³

et al. 2005

J. Neurosci.

156

153

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show abstract

The expression of cerebellar LTD in culture is not associated with changes in AMPA-receptor kinetics, agonist affinity, or unitary conductance

Cited by 57 publications

References 28 publications

Impaired Locomotor Learning and Altered Cerebellar Synaptic Plasticity in pep-19/pcp4-Null Mice

Impaired Locomotor Learning and Altered Cerebellar Synaptic Plasticity in pep-19/pcp4-Null Mice

A Stochastic Signaling Network Mediates the Probabilistic Induction of Cerebellar Long-Term Depression

Number and Density of AMPA Receptors in Single Synapses in Immature Cerebellum

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