scholarly journals Post-tetanic increase in the fast-releasing synaptic vesicle pool at the expense of the slowly releasing pool

2010 ◽  
Vol 136 (3) ◽  
pp. 259-272 ◽  
Author(s):  
Jae Sung Lee ◽  
Won-Kyung Ho ◽  
Suk-Ho Lee
Keyword(s):  
Synaptic Vesicles ◽  
Late Phase ◽  
High Frequency Stimulation ◽  
First Line ◽  
Pipette Solution ◽  
Readily Releasable Pool ◽  
Whole Cell Patch Clamp ◽  
Frequency Stimulation ◽  
Post Tetanic Potentiation ◽  
Vesicle Pool

Post-tetanic potentiation (PTP) at the calyx of Held synapse is caused by increases not only in release probability (Pr) but also in the readily releasable pool size estimated from a cumulative plot of excitatory post-synaptic current amplitudes (RRPcum), which contribute to the augmentation phase and the late phase of PTP, respectively. The vesicle pool dynamics underlying the latter has not been investigated, because PTP is abolished by presynaptic whole-cell patch clamp. We found that supplement of recombinant calmodulin to the presynaptic pipette solution rescued the increase in the RRPcum after high-frequency stimulation (100 Hz for 4-s duration, HFS), but not the increase in Pr. Release-competent synaptic vesicles (SVs) are heterogeneous in their releasing kinetics. To investigate post-tetanic changes of fast and slowly releasing SV pool (FRP and SRP) sizes, we estimated quantal release rates before and 40 s after HFS using the deconvolution method. After HFS, the FRP size increased by 19.1% and the SRP size decreased by 25.4%, whereas the sum of FRP and SRP sizes did not increase. Similar changes in the RRP were induced by a single long depolarizing pulse (100 ms). The post-tetanic complementary changes of FRP and SRP sizes were abolished by inhibitors of myosin II or myosin light chain kinase. The post-tetanic increase in the FRP size coupled to a decrease in the SRP size provides the first line of evidence for the idea that a slowly releasing SV can be converted to a fast releasing one.

scholarly journals Frequency-dependent mobilization of heterogeneous pools of synaptic vesicles shapes presynaptic plasticity

eLife ◽  
2017 ◽  
Vol 6 ◽  
Author(s):  
Frédéric Doussau ◽  
Hartmut Schmidt ◽  
Kevin Dorgans ◽  
Antoine M Valera ◽  
Bernard Poulain ◽  
...  
Keyword(s):  
Synaptic Vesicles ◽  
Granule Cells ◽  
Low Frequency ◽  
Synaptic Activity ◽  
High Frequency Stimulation ◽  
Frequency Dependent ◽  
Short Term Plasticity ◽  
Readily Releasable Pool ◽  
Frequency Stimulation ◽  
Sensorimotor Information

The segregation of the readily releasable pool of synaptic vesicles (RRP) in sub-pools that are differentially poised for exocytosis shapes short-term plasticity. However, the frequency-dependent mobilization of these sub-pools is poorly understood. Using slice recordings and modeling of synaptic activity at cerebellar granule cell to Purkinje cell synapses of mice, we describe two sub-pools in the RRP that can be differentially recruited upon ultrafast changes in the stimulation frequency. We show that at low-frequency stimulations, a first sub-pool is gradually silenced, leading to full blockage of synaptic transmission. Conversely, a second pool of synaptic vesicles that cannot be released by a single stimulus is recruited within milliseconds by high-frequency stimulation and support an ultrafast recovery of neurotransmitter release after low-frequency depression. This frequency-dependent mobilization or silencing of sub-pools in the RRP in terminals of granule cells may play a role in the filtering of sensorimotor information in the cerebellum.

scholarly journals A frequency-dependent mobilization of heterogeneous pools of synaptic vesicles shapes presynaptic plasticity

2017 ◽  
Author(s):  
Frédéric Doussau ◽  
Hartmut Schmidt ◽  
Kevin Dorgans ◽  
Antoine M. Valera ◽  
Bernard Poulain ◽  
...  
Keyword(s):  
Granule Cell ◽  
Synaptic Vesicles ◽  
Low Frequency ◽  
Synaptic Activity ◽  
High Frequency Stimulation ◽  
Frequency Dependent ◽  
Readily Releasable Pool ◽  
Low Frequency Stimulation ◽  
Frequency Stimulation

ABSTRACTThe segregation of the readily releasable pool of synaptic vesicles (RRP) in sub-pool which are differentially poised for exocytosis shapes short-term plasticity at depressing synapses. Here, we used in vitro recording and modeling of synaptic activity at the facilitating mice cerebellar granule cell to Purkinje cell synapse to demonstrate the existence of two sub-pools of vesicles in the RRP that can be differentially recruited upon fast changes in the stimulation frequency. We show that upon low-frequency stimulation, a population of fully-releasable vesicles is silenced, leading to full blockage of synaptic transmission. A second population of vesicles, reluctant to release by simple stimuli, is recruited in a millisecond time scale by high-frequency stimulation to support an ultrafast recovery of neurotransmitter release after low-frequency depression. The frequency-dependent mobilization or silencing of sub-pools of vesicles in granule cell terminals should play a major role in the filtering of sensorimotor information in the cerebellum.

The Same Synaptic Vesicles Originate Synchronous and Asynchronous Transmitter Release

Acta Naturae ◽  
2015 ◽  
Vol 7 (3) ◽  
pp. 81-88 ◽  
Author(s):  
P. N. Grigoryev ◽  
A. L. Zefirov
Keyword(s):  
Synaptic Vesicle ◽  
High Frequency ◽  
Transmitter Release ◽  
Synaptic Vesicles ◽  
High Frequency Stimulation ◽  
Vesicle Pools ◽  
Bivalent Cations ◽  
Frequency Stimulation ◽  
Nerve Muscle ◽  
Vesicle Pool

Transmitter release and synaptic vesicle exo- and endocytosis during high-frequency stimulation (20 pulses/s) in the extracellular presence of different bivalent cations (Ca2+, Sr2+ or Ba2+) were studied in frog cutaneous pectoris nerve-muscle preparations. It was shown in electrophysiological experiments that almost only synchronous transmitter release was registered in a Ca2+-containing solution; a high intensity of both synchronous and asynchronous transmitter release was registered in a Sr2+-containing solution, and asynchronous transmitter release almost only was observed in a Ba2+-containing solution. It was shown in experiments with a FM 1-43 fluorescent dye that the synaptic vesicles that undergo exocytosis-endocytosis during synchronous transmitter release (Ca-solutions) are able to participate in asynchronous exocytosis in Ba-solutions. The vesicles that had participated in the asynchronous transmitter release (Ba-solutions) could subsequently participate in a synchronous release (Ca-solutions). It was shown in experiments with isolated staining of recycling and reserve synaptic vesicle pools that both types of evoked transmitter release originate from the same synaptic vesicle pool.

scholarly journals Determinants of synaptic strength vary across an axon arbor

2012 ◽  
Vol 107 (9) ◽  
pp. 2430-2441 ◽  
Author(s):  
Xiaoyu Peng ◽  
Thomas D. Parsons ◽  
Rita J. Balice-Gordon
Keyword(s):  
Synaptic Vesicles ◽  
Hippocampal Neurons ◽  
Synaptic Strength ◽  
Pool Size ◽  
Spatial Modulation ◽  
Readily Releasable Pool ◽  
Single Axon ◽  
Individual Vesicle ◽  
Highly Correlated ◽  
Vesicle Pool

We used synaptophysin-pHluorin expressed in hippocampal neurons to address how functional properties of terminals, namely, evoked release, total vesicle pool size, and release fraction, vary spatially across individual axon arbors. Consistent with previous reports, over short arbor distances (∼100 μm), evoked release was spatially heterogeneous when terminals contacted different postsynaptic dendrites or neurons. Regardless of the postsynaptic configuration, the evoked release and total vesicle pool size spatially covaried, suggesting that the fraction of synaptic vesicles available for release (release fraction) was similar over short distances. Evoked release and total vesicle pool size were highly correlated with the amount of NMDA receptors and PSD-95 in postsynaptic specialization. However, when individual axons were followed over longer distances (several hundred micrometers), a significant increase in evoked release was observed distally that was associated with an increased release fraction in distal terminals. The increase in distal release fraction can be accounted for by changes in individual vesicle release probability as well as readily releasable pool size. Our results suggest that for a single axon arbor, presynaptic strength indicated by evoked release over short distances is correlated with heterogeneity in total vesicle pool size, whereas over longer distances presynaptic strength is correlated with the spatial modulation of release fraction. Thus the mechanisms that determine synaptic strength differ depending on spatial scale.

Differential Effects of SNAP-25 Deletion on Ca2+-Dependent and Ca2+-Independent Neurotransmission

2007 ◽  
Vol 98 (2) ◽  
pp. 794-806 ◽  
Author(s):  
Peter Bronk ◽  
Ferenc Deák ◽  
Michael C. Wilson ◽  
Xinran Liu ◽  
Thomas C. Südhof ◽  
...  
Keyword(s):  
Neurotransmitter Release ◽  
High Frequency Stimulation ◽  
Neuronal Cultures ◽  
Inhibitory Neurotransmitter ◽  
Calcium Dependent ◽  
Receptor Complexes ◽  
Readily Releasable Pool ◽  
Protein Receptor ◽  
Frequency Stimulation ◽  
Hypertonic Stimulation

At the synapse, SNAP-25, along with syntaxin/HPC-1 and synaptobrevin/VAMP, forms SNARE N-ethylmaleimide-sensitive factor [soluble (NSF) attachment protein receptor] complexes that are thought to catalyze membrane fusion. Results from neuronal cultures of synaptobrevin-2 knockout (KO) mice showed that loss of synaptobrevin has a more severe effect on calcium-evoked release than on spontaneous release or on release evoked by hypertonicity. In this study, we recorded neurotransmitter release from neuronal cultures of SNAP-25 KO mice to determine whether they share this property. In neurons lacking SNAP-25, as those deficient in synaptobrevin-2, we found that ∼10–12% of calcium-independent excitatory and inhibitory neurotransmitter release persisted. However, in contrast to synaptobrevin-2 knockouts, this remaining readily releasable pool in SNAP-25-deficient synapses was virtually insensitive to calcium-dependent–evoked stimulation. Although field stimulation reliably evoked neurotransmitter release in synaptobrevin-2 KO neurons, responses were rare in neurons lacking SNAP-25, and unlike synaptobrevin-2–deficient synapses, SNAP-25–deficient synapses did not exhibit facilitation of release during high-frequency stimulation. This severe loss of evoked exocytosis was matched by a reduction, but not a complete loss, of endocytosis during evoked stimulation. Moreover, synaptic vesicle turnover probed by FM-dye uptake and release during hypertonic stimulation was relatively unaffected by the absence of SNAP-25. This last difference indicates that in contrast to synaptobrevin, SNAP-25 does not directly function in endocytosis. Together, these results suggest that SNAP-25 has a more significant role in calcium-secretion coupling than synaptobrevin-2.

scholarly journals Deep brain stimulation: increasing efficiency by alternative waveforms

2016 ◽  
Vol 2 (1) ◽  
pp. 145-148 ◽  
Author(s):  
Katerina Argiti ◽  
Kevin Joseph ◽  
Soheil Mottaghi ◽  
Thomas J. Feuerstein ◽  
Ulrich G. Hofmann
Keyword(s):  
Deep Brain Stimulation ◽  
Brain Stimulation ◽  
Brain Slices ◽  
Pyramidal Cells ◽  
High Frequency Stimulation ◽  
Whole Cell Patch Clamp ◽  
Frequency Stimulation ◽  
Patch Clamp Electrophysiology ◽  
Deep Brain

AbstractDeep brain stimulation (DBS) is based on the effect of high frequency stimulation (HFS) in neuronal tissue. As a therapy option for patients suffering from e.g. Parkinson’s disease, DBS has been used for decades. Despite the widespread use, the effect of HFS on neurons is not fully investigated. Improving the stimulation efficiency und specificity could increase the efficiency of the INS (internal neuronal stimulator) as well as potentially reduce unwanted side effects. The effect of HFS on the GABAergic system was quantified using whole cell patch clamp electrophysiology during HFS stimulation in cortical human brain slices in vitro. Rectangular, sine, sawtooth and triangular waveforms were applied extracellularly. Since HFS has been hypothesized to increase the activity of the axons of GABAergic interneurons, a decrease in activity can be observed in the pyramidal cells that the interneurons project to. By isolating the incoming non- GABAergic events, we can filter out only the GABAA currents which can be verified using a GABAA antagonist. The results show that all the waveforms effectively increase the GABAA currents. The triangle waveform causes the highest significant increase in the activity which further increases over time after the stimulation was turned off.

scholarly journals Transsynaptic modulation of presynaptic short-term plasticity in hippocampal mossy fiber synapses

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
David Vandael ◽  
Yuji Okamoto ◽  
Peter Jonas
Keyword(s):  
Pyramidal Neurons ◽  
Mossy Fiber ◽  
Brain Slices ◽  
High Frequency Stimulation ◽  
Short Term Plasticity ◽  
Glutamate Signaling ◽  
Frequency Stimulation ◽  
Post Tetanic Potentiation ◽  
Mossy Fiber Synapse ◽  
Ca3 Neurons

AbstractThe hippocampal mossy fiber synapse is a key synapse of the trisynaptic circuit. Post-tetanic potentiation (PTP) is the most powerful form of plasticity at this synaptic connection. It is widely believed that mossy fiber PTP is an entirely presynaptic phenomenon, implying that PTP induction is input-specific, and requires neither activity of multiple inputs nor stimulation of postsynaptic neurons. To directly test cooperativity and associativity, we made paired recordings between single mossy fiber terminals and postsynaptic CA3 pyramidal neurons in rat brain slices. By stimulating non-overlapping mossy fiber inputs converging onto single CA3 neurons, we confirm that PTP is input-specific and non-cooperative. Unexpectedly, mossy fiber PTP exhibits anti-associative induction properties. EPSCs show only minimal PTP after combined pre- and postsynaptic high-frequency stimulation with intact postsynaptic Ca2+ signaling, but marked PTP in the absence of postsynaptic spiking and after suppression of postsynaptic Ca2+ signaling (10 mM EGTA). PTP is largely recovered by inhibitors of voltage-gated R- and L-type Ca2+ channels, group II mGluRs, and vacuolar-type H+-ATPase, suggesting the involvement of retrograde vesicular glutamate signaling. Transsynaptic regulation of PTP extends the repertoire of synaptic computations, implementing a brake on mossy fiber detonation and a “smart teacher” function of hippocampal mossy fiber synapses.

scholarly journals Superpriming of synaptic vesicles as a common basis for intersynapse variability and modulation of synaptic strength

2016 ◽  
Vol 113 (31) ◽  
pp. E4548-E4557 ◽  
Author(s):  
Holger Taschenberger ◽  
Andrew Woehler ◽  
Erwin Neher
Keyword(s):  
Synaptic Vesicles ◽  
Low Frequency ◽  
Synaptic Strength ◽  
High Frequency Stimulation ◽  
Short Term ◽  
Release Probability ◽  
Common Basis ◽  
Frequency Stimulation ◽  
Increased Strength ◽  
The Impact

Glutamatergic synapses show large variations in strength and short-term plasticity (STP). We show here that synapses displaying an increased strength either after posttetanic potentiation (PTP) or through activation of the phospholipase-C–diacylglycerol pathway share characteristic properties with intrinsically strong synapses, such as (i) pronounced short-term depression (STD) during high-frequency stimulation; (ii) a conversion of that STD into a sequence of facilitation followed by STD after a few conditioning stimuli at low frequency; (iii) an equalizing effect of such conditioning stimulation, which reduces differences among synapses and abolishes potentiation; and (iv) a requirement of long periods of rest for reconstitution of the original STP pattern. These phenomena are quantitatively described by assuming that a small fraction of “superprimed” synaptic vesicles are in a state of elevated release probability (p ∼ 0.5). This fraction is variable in size among synapses (typically about 30%), but increases after application of phorbol ester or during PTP. The majority of vesicles, released during repetitive stimulation, have low release probability (p ∼ 0.1), are relatively uniform in number across synapses, and are rapidly recruited. In contrast, superprimed vesicles need several seconds to be regenerated. They mediate enhanced synaptic strength at the onset of burst-like activity, the impact of which is subject to modulation by slow modulatory transmitter systems.

Changes in the Readily Releasable Pool of Transmitter and in Efficacy of Release Induced by High-Frequency Firing at Aplysia Sensorimotor Synapses in Culture

2004 ◽  
Vol 91 (4) ◽  
pp. 1500-1509 ◽  
Author(s):  
Yali Zhao ◽  
Marc Klein
Keyword(s):  
Motor Neuron ◽  
High Frequency ◽  
Transmitter Release ◽  
Action Potentials ◽  
High Frequency Stimulation ◽  
Hypertonic Solution ◽  
Posttetanic Potentiation ◽  
Releasable Pool ◽  
Readily Releasable Pool ◽  
Frequency Stimulation

Synaptic transmission at the sensory neuron-motor neuron synapses of Aplysia, like transmission at many synapses of both vertebrates and invertebrates, is increased after a short burst of high-frequency stimulation (HFS), a phenomenon known as posttetanic potentiation (PTP). PTP is generally attributable to an increase in transmitter release from presynaptic neurons. We investigated whether changes in the readily releasable pool of transmitter (RRP) contribute to the potentiation that follows HFS. We compared the changes in excitatory postsynaptic potentials (EPSPs) evoked with action potentials to changes in the RRP as estimated from the asynchronous transmitter release elicited by a hypertonic solution. The changes in the EPSP were correlated with changes in the RRP, but the changes matched quantitatively only at connections whose initial synaptic strength was greater than the median for all experiments. At weaker connections, the increase in the RRP was insufficient to account for PTP. Weaker connections initially released a smaller fraction of the RRP with each EPSP than stronger ones, and this fraction increased at weaker connections after HFS. Moreover, the initial transmitter release in response to the hypertonic solution was accelerated after HFS, indicating that the increase in the efficacy of release was not restricted to excitation-secretion coupling. Modulation of the RRP and of the efficacy of release thus both contribute to the enhancement of transmitter release by HFS.

scholarly journals Cholinergic mechanisms of high-frequency stimulation in entopeduncular nucleus

2016 ◽  
Vol 115 (1) ◽  
pp. 60-67 ◽  
Author(s):  
Feng Luo ◽  
Zelma H. T. Kiss
Keyword(s):  
High Frequency ◽  
Receptor Activation ◽  
Inhibitory Synapses ◽  
High Frequency Stimulation ◽  
Entopeduncular Nucleus ◽  
Cellular Mechanisms ◽  
Cholinergic Mechanism ◽  
Whole Cell Patch Clamp ◽  
Frequency Stimulation ◽  
Underlying Mechanisms

Chronic, high-frequency (>100 Hz) electrical stimulation, known as deep brain stimulation (DBS), of the internal segment of the globus pallidus (GPi) is a highly effective therapy for Parkinson's disease (PD) and dystonia. Despite some understanding of how it works acutely in PD models, there remain questions about its mechanisms of action. Several hypotheses have been proposed, such as depolarization blockade, activation of inhibitory synapses, depletion of neurotransmitters, and/or disruption/alteration of network oscillations. In this study we investigated the cellular mechanisms of high-frequency stimulation (HFS) in entopeduncular nucleus (EP; rat equivalent of GPi) neurons using whole cell patch-clamp recordings. We found that HFS applied inside the EP nucleus induced a prolonged afterdepolarization that was dependent on stimulation frequency, pulse duration, and current amplitude. The high frequencies (>100 Hz) and pulse widths (>0.15 ms) used clinically for dystonia DBS could reliably induce these afterdepolarizations, which persisted under blockade of ionotropic glutamate (kynurenic acid, 2 mM), GABAA (picrotoxin, 50 μM), GABAB (CGP 55845, 1 μM), and acetylcholine nicotinic receptors (DHβE, 2 μM). However, this effect was blocked by atropine (2 μM; nonselective muscarinic antagonist) or tetrodotoxin (0.5 μM). Finally, the muscarinic-dependent afterdepolarizations were sensitive to Ca2+-sensitive nonspecific cationic (CAN) channel blockade. Hence, these data suggest that muscarinic receptor activation during HFS can lead to feedforward excitation through the opening of CAN channels. This study for the first time describes a cholinergic mechanism of HFS in EP neurons and provides new insight into the underlying mechanisms of DBS.

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