Synapsin Controls Both Reserve and Releasable Synaptic Vesicle Pools during Neuronal Activity and Short-Term Plasticity inAplysia

Synaptic vesicle (SV) release, recycling, and plastic changes of release probability co-occur side by side within nerve terminals and rely on local Ca2+ signals with different temporal and spatial profiles. The mechanisms that guarantee separate regulation of these vital presynaptic functions during action potential (AP)–triggered presynaptic Ca2+ entry remain unclear. Combining Drosophila genetics with electrophysiology and imaging reveals the localization of two different voltage-gated calcium channels at the presynaptic terminals of glutamatergic neuromuscular synapses (the Drosophila Cav2 homolog, Dmca1A or cacophony, and the Cav1 homolog, Dmca1D) but with spatial and functional separation. Cav2 within active zones is required for AP-triggered neurotransmitter release. By contrast, Cav1 localizes predominantly around active zones and contributes substantially to AP-evoked Ca2+ influx but has a small impact on release. Instead, L-type calcium currents through Cav1 fine-tune short-term plasticity and facilitate SV recycling. Separate control of SV exo- and endocytosis by AP-triggered presynaptic Ca2+ influx through different channels demands efficient measures to protect the neurotransmitter release machinery against Cav1-mediated Ca2+ influx. We show that the plasma membrane Ca2+ ATPase (PMCA) resides in between active zones and isolates Cav2-triggered release from Cav1-mediated dynamic regulation of recycling and short-term plasticity, two processes which Cav2 may also contribute to. As L-type Cav1 channels also localize next to PQ-type Cav2 channels within axon terminals of some central mammalian synapses, we propose that Cav2, Cav1, and PMCA act as a conserved functional triad that enables separate control of SV release and recycling rates in presynaptic terminals.

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Cognitive impairment in Gdi1-deficient mice is associated with altered synaptic vesicle pools and short-term synaptic plasticity, and can be corrected by appropriate learning training

Human Molecular Genetics ◽

10.1093/hmg/ddn321 ◽

2008 ◽

Vol 18 (1) ◽

pp. 105-117 ◽

Cited By ~ 38

Author(s):

Veronica Bianchi ◽

Pasqualina Farisello ◽

Pietro Baldelli ◽

Virginia Meskenaite ◽

Marco Milanese ◽

...

Keyword(s):

Cognitive Impairment ◽

Synaptic Plasticity ◽

Synaptic Vesicle ◽

Short Term ◽

Vesicle Pools ◽

Deficient Mice

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Dynamic Control of Synaptic Vesicle Replenishment and Short-Term Plasticity by Ca2+-Calmodulin-Munc13-1 Signaling

Neuron ◽

10.1016/j.neuron.2013.05.011 ◽

2013 ◽

Vol 79 (1) ◽

pp. 82-96 ◽

Cited By ~ 80

Author(s):

Noa Lipstein ◽

Takeshi Sakaba ◽

Benjamin H. Cooper ◽

Kun-Han Lin ◽

Nicola Strenzke ◽

...

Keyword(s):

Synaptic Vesicle ◽

Dynamic Control ◽

Short Term ◽

Short Term Plasticity

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Circuit mechanisms for the maintenance and manipulation of information in working memory

10.1101/305714 ◽

2018 ◽

Cited By ~ 7

Author(s):

Nicolas Y. Masse ◽

Guangyu R. Yang ◽

H. Francis Song ◽

Xiao-Jing Wang ◽

David J. Freedman

Keyword(s):

Working Memory ◽

Neuronal Activity ◽

Short Term Memory ◽

Current Debate ◽

Memory Representation ◽

Short Term ◽

Short Term Plasticity ◽

Hidden States ◽

Dependent Tasks ◽

External Stimuli

SummaryRecently it has been proposed that information in short-term memory may not always be stored in persistent neuronal activity, but can be maintained in “activity-silent” hidden states such as synaptic efficacies endowed with short-term plasticity (STP). However, working memory involves manipulation as well as maintenance of information in the absence of external stimuli. In this work, we investigated working memory representation using recurrent neural network (RNN) models trained to perform several working memory dependent tasks. We found that STP can support the short-term maintenance of information provided that the memory delay period is sufficiently short. However, in tasks that require actively manipulating information, persistent neuronal activity naturally emerges from learning, and the amount of persistent neuronal activity scales with the degree of manipulation required. These results shed insight into the current debate on working memory encoding, and suggest that persistent neural activity can vary markedly between tasks used in different experiments.

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Translating Neuronal Activity at the Synapse: The Role of the Protein Kinase C Cascade in Short-Term Plasticity

Biophysical Journal ◽

10.1016/j.bpj.2017.11.1096 ◽

2018 ◽

Vol 114 (3) ◽

pp. 196a

Author(s):

Diasynou Fioravante

Keyword(s):

Protein Kinase C ◽

Protein Kinase ◽

Neuronal Activity ◽

Short Term ◽

Short Term Plasticity ◽

Kinase C

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Overexpression of synapsin Ia in the rat calyx of Held accelerates short-term plasticity and decreases synaptic vesicle volume and active zone area

Frontiers in Cellular Neuroscience ◽

10.3389/fncel.2013.00270 ◽

2013 ◽

Vol 7 ◽

Cited By ~ 3

Author(s):

Mariya Vasileva ◽

Robert Renden ◽

Heinz Horstmann ◽

Daniel Gitler ◽

Thomas Kuner

Keyword(s):

Synaptic Vesicle ◽

Active Zone ◽

Short Term ◽

Calyx Of Held ◽

Short Term Plasticity

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Downstream Effect of Ramping Neuronal Activity through Synapses with Short-Term Plasticity

Neural Computation ◽

10.1162/neco_a_00818 ◽

2016 ◽

Vol 28 (4) ◽

pp. 652-666 ◽

Cited By ~ 1

Author(s):

Wei Wei ◽

Xiao-Jing Wang

Keyword(s):

Neuronal Activity ◽

Time Constant ◽

Task Difficulty ◽

Perceptual Decision Making ◽

Short Term ◽

Short Term Plasticity ◽

A Value ◽

Analytical Result ◽

Decision Circuit ◽

The Impact

Ramping neuronal activity refers to spiking activity with a rate that increases quasi-linearly over time. It has been observed in multiple cortical areas and is correlated with evidence accumulation processes or timing. In this work, we investigated the downstream effect of ramping neuronal activity through synapses that display short-term facilitation (STF) or depression (STD). We obtained an analytical result for a synapse driven by deterministic linear ramping input that exhibits pure STF or STD and numerically investigated the general case when a synapse displays both STF and STD. We show that the analytical deterministic solution gives an accurate description of the averaging synaptic activation of many inputs converging onto a postsynaptic neuron, even when fluctuations in the ramping input are strong. Activation of a synapse with STF shows an initial cubical increase with time, followed by a linear ramping similar to a synapse without STF. Activation of a synapse with STD grows in time to a maximum before falling and reaching a plateau, and this steady state is independent of the slope of the ramping input. For a synapse displaying both STF and STD, an increase in the depression time constant from a value much smaller than the facilitation time constant [Formula: see text] to a value much larger than [Formula: see text] leads to a transition from facilitation dominance to depression dominance. Therefore, our work provides insights into the impact of ramping neuronal activity on downstream neurons through synapses that display short-term plasticity. In a perceptual decision-making process, ramping activity has been observed in the parietal and prefrontal cortices, with a slope that decreases with task difficulty. Our work predicts that neurons downstream from such a decision circuit could instead display a firing plateau independent of the task difficulty, provided that the synaptic connection is endowed with short-term depression.

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