An NMDA Receptor/Nitric Oxide Cascade in Presynaptic Parallel Fiber–Purkinje Neuron Long-Term Potentiation

Qiu, De-Lai; Knöpfel, Thomas

doi:10.1523/jneurosci.4831-06.2007

Cited by 60 publications

(82 citation statements)

References 31 publications

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“…PreLTD can be efficiently induced with 4 Hz PF stimulation and is prevented by an endocannabinoid CB1 receptor antagonist. Along with our recent results on preLTP [33], a scheme emerges where the induction of presynaptic PF-PN plasticity is mediated by humoral factors (endocannabinoids and NO) that may be released from molecular layer interneurons.…”

Section: Introductionsupporting

confidence: 52%

“…Paired-pulse ratio (PPR) at PF-PN synapses is a sensitive indicator of presynaptic calcium dynamics and its alteration by exogenous Ca 2+ buffers [3] but did not differ between wild-type (WT) and GCaMP2 mice (PPR at 50 ms interpulse interval, WT=2.11±0.07, n=14; GCaMP2=2.01±0.09, n=7, p= 0.4) [33]. We, therefore, concluded that calcium dynamics are not adversely affected by the presence of GCaMP2 in our mice.…”

Section: Hz Stimulation Induced a Cb1 Receptor-dependent Ltd At Pf-pnmentioning

confidence: 96%

“…We found that preLTP is protein kinase A (PKA)-dependent and requires the activation of an NMDA/ nitric oxide (NO) pathway [33]. In the course of this previous study, we noted that after the prevention of LTP by the PKA inhibitor H-89, 4 Hz stimulation caused a persistent depression of PF Ca 2+ transients (preLTD).…”

Section: Hz Stimulation Induced a Cb1 Receptor-dependent Ltd At Pf-pnmentioning

confidence: 99%

“…Because the observations made in Qiu and Knöpfel [33] were based on recordings made in mice that express the calcium sensor GCaMP2 in their parallel fibers, it could be argued that the presence of the calcium sensor may have altered PF calcium dynamics and plasticity. Paired-pulse ratio (PPR) at PF-PN synapses is a sensitive indicator of presynaptic calcium dynamics and its alteration by exogenous Ca 2+ buffers [3] but did not differ between wild-type (WT) and GCaMP2 mice (PPR at 50 ms interpulse interval, WT=2.11±0.07, n=14; GCaMP2=2.01±0.09, n=7, p= 0.4) [33].…”

Section: Hz Stimulation Induced a Cb1 Receptor-dependent Ltd At Pf-pnmentioning

confidence: 99%

“…Presynaptic expression of PF-PN LTP (preLTP) had already been demonstrated some years before [38]. We recently provided evidence for an NMDA-NO pathway in preLTP that suggested a heterosynaptic mechanism with activation of interneurons [33]. However, the complementing LTD at the presynaptic site (preLTD) has, to date, remained elusive.…”

Section: Introductionmentioning

confidence: 99%

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Presynaptically expressed long-term depression at cerebellar parallel fiber synapses

Qiu

Knöpfel

2008

Pflugers Arch - Eur J Physiol

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Plasticity at synapses between parallel fiber (PF) and Purkinje neurons (PN) is widely accepted as a cellular model for certain forms of cerebellar learning. Although PF-PN synapses are known to express bidirectional longterm plasticity at the postsynaptic site, long-term plasticity at the presynaptic site is currently limited to potentiation of the synapses. In this paper, we report on presynaptically expressed PF long-term depression (preLTD) that is observed when presynaptically expressed PF long-term potentiation (preLTP) is pharmacologically prevented. PF preLTD is most efficiently induced by 4 Hz PF stimulation and requires activation of cannabinoid CB1 receptors. Our results indicate that, during preLTD induction, endocannabinoids are released in an NMDA receptor-dependent, but not mGlu1 receptor-dependent, fashion. We conclude that bidirectional plasticity mechanisms exist for both presynaptic and postsynaptic components of cerebellar learning.

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Section: Introductionsupporting

confidence: 52%

Section: Hz Stimulation Induced a Cb1 Receptor-dependent Ltd At Pf-pnmentioning

confidence: 96%

Section: Hz Stimulation Induced a Cb1 Receptor-dependent Ltd At Pf-pnmentioning

confidence: 99%

Section: Hz Stimulation Induced a Cb1 Receptor-dependent Ltd At Pf-pnmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Presynaptically expressed long-term depression at cerebellar parallel fiber synapses

Qiu

Knöpfel

2008

Pflugers Arch - Eur J Physiol

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Plasticity in the Cerebellar Cortex

Broussard¹

2013

The Cerebellum

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Deletion of the cannabinoid CB₁ receptor impacts on the ultrastructure of the cerebellar parallel fiber‐Purkinje cell synapses

Buceta

Elezgarai

Rico‐Barrio

et al. 2019

J of Comparative Neurology

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The cannabinoid CB 1 receptor localizes to the glutamatergic parallel fiber (PF) terminals of the cerebellar granule cells and participates in synaptic plasticity, motor control and learning that are impaired in CB 1 receptor knockout (CB 1 -KO) mice. However, whether ultrastructural changes at the PF-Purkinje cell (PC) synapses occur in CB 1 -KO remains unknown. We studied this in the vermis of the spinocerebellar lobule V and the vestibulocerebellar lobule X of CB 1 -KO and wild-type (CB 1 -WT) mice by electron microscopy. Lobule V, but not lobule X, of CB 1 -KO had significantly less and longer synapses than in CB 1 -WT. PF terminals were significantly larger in both lobules of CB 1 -KO with no changes in PC dendritic spines. The PF terminals in lobule V of CB 1 -KO contained less synaptic vesicles and lower vesicle density; by contrast, vesicle density in lobule X of CB 1 -KO remained unchangeable relative to CB 1 -WT. There were as many vesicles in lobule V of CB 1 -KO as in CB 1 -WT, but their distribution decreased drastically at 300 nm of the active zone. In lobule X of CB 1 -KO, less vesicles were found within 150 nm from the presynaptic membrane; however, no vesicles were at 450-600 nm of the active zone. A significant higher amount of synaptic vesicles close to the active zone in lobule V and X of CB 1 -KO was observed. In conclusion, the absence of CB 1 receptors strikingly and distinctively impacts on the ultrastructural architecture of the PF-PC synapses located in cerebellar lobules that differ in vulnerability to damage and motor functions.

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An NMDA Receptor/Nitric Oxide Cascade in Presynaptic Parallel Fiber–Purkinje Neuron Long-Term Potentiation

Abstract: Plasticity of synaptic transmission between parallel fiber (PF) and Purkinje neurons (PNs

Cited by 60 publications

References 31 publications

Presynaptically expressed long-term depression at cerebellar parallel fiber synapses

Presynaptically expressed long-term depression at cerebellar parallel fiber synapses

Plasticity in the Cerebellar Cortex

Deletion of the cannabinoid CB₁ receptor impacts on the ultrastructure of the cerebellar parallel fiber‐Purkinje cell synapses

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An NMDA Receptor/Nitric Oxide Cascade in Presynaptic Parallel Fiber–Purkinje Neuron Long-Term Potentiation

Abstract: Plasticity of synaptic transmission between parallel fiber (PF) and Purkinje neurons (PNs

Cited by 60 publications

References 31 publications

Presynaptically expressed long-term depression at cerebellar parallel fiber synapses

Presynaptically expressed long-term depression at cerebellar parallel fiber synapses

Plasticity in the Cerebellar Cortex

Deletion of the cannabinoid CB1 receptor impacts on the ultrastructure of the cerebellar parallel fiber‐Purkinje cell synapses

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Product

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Deletion of the cannabinoid CB₁ receptor impacts on the ultrastructure of the cerebellar parallel fiber‐Purkinje cell synapses