A stable proportion of Purkinje cell inputs from parallel fibers are silent during cerebellar maturation

The cerebellum is classically associated with fine motor control, motor learning, and timing of actions. However, while its anatomy is well described and many synaptic plasticity have been identified, the computation performed by the cerebellar cortex is still debated. We, here, review recent advances on how the description of the functional synaptic connectivity between granule cells and Purkinje cells support the hypothesis that the cerebellum stores internal models of the body coordinates. We propose that internal models are specific of the task and of the locomotor context of each individual.

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“…1A, C). Silent synapses were also recently observed during development and in adult rodents [24,63].…”

Section: Spatially Organized Gc-pc Connectivity Maps As An Implementa...mentioning

confidence: 75%

What Can We Learn from Synaptic Connectivity Maps about Cerebellar Internal Models?

Spaeth

Isope

2022

Cerebellum

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“…This conclusion was reached because only 7% of stimulated granule cells generated electric responses in the soma of Purkinje cells, as opposed to the expected ~54% based on the anatomical count of spines and synapses ( Napper and Harvey, 1988a ; Napper and Harvey, 1988b ). A recent study in slices also found that more than 70% of parallel fiber synapses did not produce detectable fast postsynaptic responses ( Ho et al, 2021 ). This proportion was the same in young and adolescent mice, suggesting that it is a stable feature of the cerebellum even during development ( Ho et al, 2021 ).…”

Section: Discussionmentioning

confidence: 97%

“…A recent study in slices also found that more than 70% of parallel fiber synapses did not produce detectable fast postsynaptic responses ( Ho et al, 2021 ). This proportion was the same in young and adolescent mice, suggesting that it is a stable feature of the cerebellum even during development ( Ho et al, 2021 ). In short, there is evidence that perhaps only around 10–20% of parallel fiber synapses may be eloquent, that is, capable of eliciting currents in the soma of Purkinje cells.…”

Section: Discussionmentioning

confidence: 97%

Ultrastructural effects of sleep and wake on the parallel fiber synapses of the cerebellum

Loschky

Spano

Marshall

et al. 2022

eLife

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Multiple evidence in rodents shows that the strength of excitatory synapses in the cerebral cortex and hippocampus is greater after wake than after sleep. The widespread synaptic weakening afforded by sleep is believed to keep the cost of synaptic activity under control, promote memory consolidation, and prevent synaptic saturation, thus preserving the brain’s ability to learn day after day. The cerebellum is highly plastic and the Purkinje cells, the sole output neurons of the cerebellar cortex, are endowed with a staggering number of excitatory parallel fiber synapses. However, whether these synapses are affected by sleep and wake is unknown. Here, we used serial block face scanning electron microscopy to obtain the full 3D reconstruction of more than 7000 spines and their parallel fiber synapses in the mouse posterior vermis. This analysis was done in mice whose cortical and hippocampal synapses were previously measured, revealing that average synaptic size was lower after sleep compared to wake with no major changes in synapse number. Here, instead, we find that while the average size of parallel fiber synapses does not change, the number of branched synapses is reduced in half after sleep compared to after wake, corresponding to ~16% of all spines after wake and ~8% after sleep. Branched synapses are harbored by two or more spines sharing the same neck and, as also shown here, are almost always contacted by different parallel fibers. These findings suggest that during wake, coincidences of firing over parallel fibers may translate into the formation of synapses converging on the same branched spine, which may be especially effective in driving Purkinje cells to fire. By contrast, sleep may promote the off-line pruning of branched synapses that were formed due to spurious coincidences.

show abstract

“…This conclusion was reached because only 7% of stimulated granule cells generated electric responses in the soma of Purkinje cells, as opposed to the expected ∼ 54% based on the anatomical count of spines and synapses (Napper and Harvey, 1988b, a). A recent study in slices also found that more than 70% of parallel fiber synapses did not produce detectable fast postsynaptic responses (Ho et al, 2021). This proportion was the same in young and adolescent mice, suggesting that it is a stable feature of the cerebellum even during development (Ho et al, 2021).…”

Section: Discussionmentioning

confidence: 97%

“…A recent study in slices also found that more than 70% of parallel fiber synapses did not produce detectable fast postsynaptic responses (Ho et al, 2021). This proportion was the same in young and adolescent mice, suggesting that it is a stable feature of the cerebellum even during development (Ho et al, 2021). In short, there is evidence that perhaps only around 10 to 20% of parallel fiber synapses may be eloquent, that is, capable of eliciting currents in the soma of Purkinje cells.…”

Section: Branched Synapses As Eloquent Synapses?mentioning

confidence: 99%

Ultrastructural effects of sleep and wake on the parallel fiber synapses of the cerebellum

Loschky¹,

Spano²,

Marshall³

et al. 2022

Preprint

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Multiple evidence in rodents shows that the strength of excitatory synapses in the cerebral cortex and hippocampus is greater after wake than after sleep. The widespread synaptic weakening afforded by sleep is believed to keep the cost of synaptic activity under control, promote memory consolidation, and prevent synaptic saturation, thus preserving the brain’s ability to learn day after day. The cerebellum is highly plastic and the Purkinje cells, the sole output neurons of the cerebellar cortex, are endowed with a staggering number of excitatory parallel fiber synapses. However, whether these synapses are affected by sleep and wake is unknown. Here we used serial block face scanning electron microscopy to obtain the full 3D reconstruction of more than 7,000 spines and their parallel fiber synapses in the mouse posterior vermis. We find that most Purkinje cell spines carry a synapse, but some do not. The latter, which we call “naked” spines, are ~5% of all spines after wake but grow to ~10% of all spines after sleep. Further analysis shows that the changes in the number of naked synapses with wake and sleep can be accounted for by a change in the number of “branched” synapses, which are housed in two or more spines sharing the same neck. Thus, during sleep branched spines may lose one or more synapses or convert to single spines, while the opposite changes occur after wake. Because branched synapses almost always contact different parallel fibers, these results also suggest that during wake, coincidences of firing over parallel fibers may translate into the formation of synapses converging on the same branched spine, which may be especially effective at driving the soma of Purkinje cells. Sleep, on the other hand, may promote the pruning of branched synapses that were formed due to spurious coincidences.

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A stable proportion of Purkinje cell inputs from parallel fibers are silent during cerebellar maturation

Cited by 5 publications

References 75 publications

What Can We Learn from Synaptic Connectivity Maps about Cerebellar Internal Models?

What Can We Learn from Synaptic Connectivity Maps about Cerebellar Internal Models?

Ultrastructural effects of sleep and wake on the parallel fiber synapses of the cerebellum

Ultrastructural effects of sleep and wake on the parallel fiber synapses of the cerebellum

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