A Simple Depletion Model of the Readily Releasable Pool of Synaptic Vesicles Cannot Account for Paired-Pulse Depression

2007 ◽  
Vol 97 (1) ◽  
pp. 948-950 ◽  
Author(s):  
Jane M. Sullivan
Keyword(s):  
Synaptic Vesicles ◽  
Hippocampal Neurons ◽  
Synaptic Activity ◽  
Excitatory Synapses ◽  
Short Term ◽  
Paired Pulse ◽  
Short Term Plasticity ◽  
Releasable Pool ◽  
Readily Releasable Pool ◽  
Paired Pulse Depression

Paired-pulse depression (PPD) is a form of short-term plasticity that plays a central role in processing of synaptic activity and is manifest as a decrease in the size of the response to the second of two closely timed stimuli. Despite mounting evidence to the contrary, PPD is still commonly thought to reflect depletion of the pool of synaptic vesicles available for release in response to the second stimulus. Here it is shown that PPD cannot be accounted for by depletion at excitatory synapses made by hippocampal neurons because PPD is unaffected by changes in the fraction of the readily releasable pool (RRP) released by the first of a pair of pulses.

scholarly journals Doc2-mediated superpriming supports synaptic augmentation

2018 ◽  
Vol 115 (24) ◽  
pp. E5605-E5613 ◽  
Author(s):  
Renhao Xue ◽  
David A. Ruhl ◽  
Joseph S. Briguglio ◽  
Alexander G. Figueroa ◽  
Robert A. Pearce ◽  
...  
Keyword(s):  
Plasma Membrane ◽  
Synaptic Plasticity ◽  
Learning And Memory ◽  
Synaptic Vesicles ◽  
Hippocampal Neurons ◽  
Underlying Mechanism ◽  
Short Term ◽  
Short Term Plasticity ◽  
Releasable Pool ◽  
Readily Releasable Pool

Various forms of synaptic plasticity underlie aspects of learning and memory. Synaptic augmentation is a form of short-term plasticity characterized by synaptic enhancement that persists for seconds following specific patterns of stimulation. The mechanisms underlying this form of plasticity are unclear but are thought to involve residual presynaptic Ca2+. Here, we report that augmentation was reduced in cultured mouse hippocampal neurons lacking the Ca2+ sensor, Doc2; other forms of short-term enhancement were unaffected. Doc2 binds Ca2+ and munc13 and translocates to the plasma membrane to drive augmentation. The underlying mechanism was not associated with changes in readily releasable pool size or Ca2+ dynamics, but rather resulted from superpriming a subset of synaptic vesicles. Hence, Doc2 forms part of the Ca2+-sensing apparatus for synaptic augmentation via a mechanism that is molecularly distinct from other forms of short-term plasticity.

Net Interaction Between Different Forms of Short-Term Synaptic Plasticity and Slow-IPSPs in the Hippocampus and Auditory Cortex

1998 ◽  
Vol 80 (4) ◽  
pp. 1765-1774 ◽  
Author(s):  
Dean V. Buonomano ◽  
Michael M. Merzenich
Keyword(s):  
Synaptic Plasticity ◽  
Auditory Cortex ◽  
Hippocampal Neurons ◽  
Time Dependent ◽  
Peak Amplitude ◽  
Short Term ◽  
Paired Pulse ◽  
Postsynaptic Potentials ◽  
Short Term Plasticity ◽  
Cgp 55845

Buonomano, Dean V. and Michael M. Merzenich. Net interaction between different forms of short-term synaptic plasticity and slow-IPSPs in the hippocampus and auditory cortex. J. Neurophysiol. 80: 1765–1774, 1998. Paired-pulse plasticity is typically used to study the mechanisms underlying synaptic transmission and modulation. An important question relates to whether, under physiological conditions in which various opposing synaptic properties are acting in parallel, the net effect is facilitatory or depressive, that is, whether cells further or closer to threshold. For example, does the net sum of paired-pulse facilitation (PPF) of excitatory postsynaptic potentials (EPSPs), paired-pulse depression (PPD) of inhibitory postsynaptic potentials (IPSPs), and the hyperpolarizing slow IPSP result in depression or facilitation? Here we examine how different time-dependent properties act in parallel and examine the contribution of γ-aminobutyric acid-B (GABAB) receptors that mediate two opposing processes, the slow IPSP and PPD of the fast IPSP. Using intracellular recordings from rat CA3 hippocampal neurons and L-II/III auditory cortex neurons, we examined the postsynaptic responses to paired-pulse stimulation (with intervals between 50 and 400 ms) of the Schaffer collaterals and white matter, respectively. Changes in the amplitude, time-to-peak (TTP), and slope of each EPSP were analyzed before and after application of the GABAB antagonist CGP-55845. In both CA3 and L-II/III neurons the peak amplitude of the second EPSP was generally depressed (further from threshold) compared with the first at the longer intervals; however, these EPSPs were generally broader and exhibited a longer TTP that could result in facilitation by enhancing temporal summation. At the short intervals CA3 neurons exhibited facilitation of the peak EPSP amplitude in the absence and presence of CGP-55845. In contrast, on average L-II/III cells did not exhibit facilitation at any interval, in the absence or presence of CGP-55845. CGP-55845 generally “erased” short-term plasticity, equalizing the peak amplitude and TTP of the first and second EPSPs at longer intervals in the hippocampus and auditory cortex. These results show that it is necessary to consider all time-dependent properties to determine whether facilitation or depression will dominate under intact pharmacological conditions. Furthermore our results suggest that GABAB-dependent properties may be the major contributor to short-term plasticity on the time scale of a few hundred milliseconds and are consistent with the hypothesis that the balance of different time-dependent processes can modulate the state of networks in a complex manner and could contribute to the generation of temporally sensitive neural responses.

Augmentation Controls the Fast Rebound From Depression at Excitatory Hippocampal Synapses

2008 ◽  
Vol 99 (4) ◽  
pp. 1770-1786 ◽  
Author(s):  
Elizabeth Garcia-Perez ◽  
John F. Wesseling
Keyword(s):  
Neurotransmitter Release ◽  
Single Pulse ◽  
Maximal Level ◽  
Short Term ◽  
Paired Pulse ◽  
Short Term Plasticity ◽  
Readily Releasable Pool ◽  
Hippocampal Synapses ◽  
Low Probability ◽  
Chemical Synapses

Short-term plasticity occurs at most central chemical synapses and includes both positive and negative components, but the principles governing interaction between components are largely unknown. The residual Ca2+ that persists in presynaptic terminals for several seconds after repetitive use is known to enhance neurotransmitter release under artificial, low probability of release conditions where depression is absent; this is termed augmentation. However, the full impact of augmentation under standard conditions at synapses where depression dominates is not known because of possibly complicated convolution with a variety of potential depression mechanisms. This report shows that residual Ca2+ continues to have a large enhancing impact on release at excitatory hippocampal synapses recovering from depression, including when only recently recruited vesicles are available for release. No evidence was found for gradual vesicle priming or for fast refilling of a highly releasable subdivision of the readily releasable pool (RRP). And decay of enhancement matched the clearance of residual Ca2+, thus matching the behavior of augmentation when studied in isolation. Because of incomplete RRP replenishment, synaptic strength was not typically increased above baseline when residual Ca2+ levels were highest. Instead residual Ca2+ caused single pulse release probability to rebound quickly from depression and then depress quickly during subsequent bursts of activity. Together, these observations can help resolve discrepancies in recent timing estimates of recovery from depression. Additionally, in contrast to results obtained under reduced release conditions, augmentation could be driven to a maximal level, occluding paired-pulse facilitation and other mechanisms that increase release efficiency.

Interactions Between Asynchronous Release and Short-Term Plasticity in the Nucleus Accumbens Slice

2006 ◽  
Vol 95 (3) ◽  
pp. 2020-2023 ◽  
Author(s):  
Gregory O. Hjelmstad
Keyword(s):  
Nucleus Accumbens ◽  
Synaptic Transmission ◽  
Short Term ◽  
Short Term Plasticity ◽  
Releasable Pool ◽  
Readily Releasable Pool ◽  
Glutamate Synapses ◽  
Asynchronous Release

Glutamate synapses in the nucleus accumbens (NAc) display asynchronous release in response to trains of stimulation. However, it is unclear what role this asynchronous release plays in synaptic transmission in this nucleus. This process was studied, specifically looking at the interaction between short-term depression and asynchronous release. These results indicate that synchronous and asynchronous release do not compete for a depleted readily releasable pool of vesicles.

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 EFFECTS OF ARTIFICIAL HYPOINSULINEMIA ON SYNAPTIC ACTIVITY AND PLASTICITY OF GLUTAMATERGIC NEUROTRANSMISSION IN CULTURE OF HIPPOCAMPAL NEURONS

2021 ◽  
Vol 67 (4) ◽  
pp. 3-11
Author(s):  
M.S. Shypshyna ◽  
◽  
K.I. Kuznetsov ◽  
S.A. Fedulova ◽  
M.S. Veselovsky ◽  
...  
Keyword(s):  
Hippocampal Neurons ◽  
Glutamate Release ◽  
Synaptic Activity ◽  
Short Term ◽  
Short Term Plasticity ◽  
Whole Cell Patch Clamp ◽  
Pulse Ratio ◽  
Coefficients Of Variation ◽  
Cultured Hippocampal Neurons

We investigated the effect of chronic hypoinsulinemia on the level of synaptic activity and short-term plasticity in cultured hippocampal neurons. Hypoinsulinemia was induced by culturing mature (16-20 days in vitro) rat’s hippocampal neurons without insulin for 1, 2, and 4 days. The control insulin concentration was 100 nM. Spontaneous and evoked glutamatergic excitatory postsynaptic currents (sEPSC and eEPSC, respectively) in these neurons were analyzed using the whole-cell patch-clamp method and the method of local electrical stimulation of individual axon. Hypoinsulinemia during the 1st, 2nd and 4th days led to significantly reduction of the mean sEPSC’s frequency to 49.9 ± 15.8% (n = 6), 8.5 ± 7.7% (n = 6) and 16.6 ± 5.2% (n = 8) respectively, relative to control. Also, there was a decrease of the average sEPSC’s amplitudes to 52.6 ± 5.5% (n = 6), 36.6 ± 5.8% (n = 6) and 43.9 ± 8.4% (n = 8), respectively, relative to control. Quantal analysis of the sEPSC’s amplitudes showed a decrease of multivesicular glutamate release at the synapses under such conditions. Hypoinsulinemia caused a shift in the direction of short-term plasticity in glutamatergic hippocampal synapses from potentiation to depression. The paired-pulse ratio decreased from 1.83 ± 0.25 in the control to 0.59 ± 0.07, 0.77 ± 0.07, and 0.80 ± 0.06 after the 1st, 2nd, and 4th days under cultivation without insulin. Accordingly, the ratio of the coefficients of variation of eEPSC’s amplitudes (CV2/ CV1) increased from 0.82 ± 0.07 to 1.30 ± 0.28, 1.52 ± 0.27, and 1.61 ± 0.24. The presented results indicate a significant reduction of synaptic activity and decrease in the probability of multivesicular release of glutamate at the synapses of cultured hippocampal neurons under hypoinsulinemia.

scholarly journals Synaptotagmin-1 and -7 Are Redundantly Essential for Maintaining the Capacity of the Readily-Releasable Pool of Synaptic Vesicles

PLoS Biology ◽  
2015 ◽  
Vol 13 (10) ◽  
pp. e1002267 ◽  
Author(s):  
Taulant Bacaj ◽  
Dick Wu ◽  
Jacqueline Burré ◽  
Robert C. Malenka ◽  
Xinran Liu ◽  
...  
Keyword(s):  
Synaptic Vesicles ◽  
Releasable Pool ◽  
Readily Releasable Pool ◽  
Synaptotagmin 1

Muscarinic presynaptic modulation in GABAergic pallidal synapses of the rat

2015 ◽  
Vol 113 (3) ◽  
pp. 796-807 ◽  
Author(s):  
Ricardo Hernández-Martínez ◽  
José J. Aceves ◽  
Pavel E. Rueda-Orozco ◽  
Teresa Hernández-Flores ◽  
Omar Hernández-González ◽  
...  
Keyword(s):  
Receptor Agonist ◽  
Projection Neurons ◽  
Quantal Content ◽  
Short Term ◽  
Paired Pulse ◽  
Short Term Plasticity ◽  
Striatal Projection Neurons ◽  
Muscarinic Cholinergic ◽  
Muscarinic Modulation

The external globus pallidus (GPe) is central for basal ganglia processing. It expresses muscarinic cholinergic receptors and receives cholinergic afferents from the pedunculopontine nuclei (PPN) and other regions. The role of these receptors and afferents is unknown. Muscarinic M1-type receptors are expressed by synapses from striatal projection neurons (SPNs). Because axons from SPNs project to the GPe, one hypothesis is that striatopallidal GABAergic terminals may be modulated by M1 receptors. Alternatively, some M1 receptors may be postsynaptic in some pallidal neurons. Evidence of muscarinic modulation in any of these elements would suggest that cholinergic afferents from the PPN, or other sources, could modulate the function of the GPe. In this study, we show this evidence using striatopallidal slice preparations: after field stimulation in the striatum, the cholinergic muscarinic receptor agonist muscarine significantly reduced the amplitude of inhibitory postsynaptic currents (IPSCs) from synapses that exhibited short-term synaptic facilitation. This inhibition was associated with significant increases in paired-pulse facilitation, and quantal content was proportional to IPSC amplitude. These actions were blocked by atropine, pirenzepine, and mamba toxin-7, suggesting that receptors involved were M1. In addition, we found that some pallidal neurons have functional postsynaptic M1 receptors. Moreover, some evoked IPSCs exhibited short-term depression and a different kind of modulation: they were indirectly modulated by muscarine via the activation of presynaptic cannabinoid CB1 receptors. Thus pallidal synapses presenting distinct forms of short-term plasticity were modulated differently.

scholarly journals A Quantitative Description of Short-Term Plasticity at Excitatory Synapses in Layer 2/3 of Rat Primary Visual Cortex

1997 ◽  
Vol 17 (20) ◽  
pp. 7926-7940 ◽  
Author(s):  
Juan A. Varela ◽  
Kamal Sen ◽  
Jay Gibson ◽  
Joshua Fost ◽  
L. F. Abbott ◽  
...  
Keyword(s):  
Visual Cortex ◽  
Primary Visual Cortex ◽  
Quantitative Description ◽  
Excitatory Synapses ◽  
Short Term ◽  
Short Term Plasticity ◽  
Layer 2
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