Development of the quantal properties of evoked and spontaneous synaptic currents at a brain synapse

Wall, Mark J.; Usowicz, Maria M.

doi:10.1038/3677

Cited by 76 publications

(95 citation statements)

References 46 publications

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“…Second, it allowed us to use quantal analysis techniques. To be successful, quantal analysis requires low levels of quantal variance, and this is aided by the fact that quantal variance decreases with age (Wall and Usowicz, 1998). We also confirmed that the peaks we identified in our amplitude histograms did indeed correspond to monoquantal responses (supplemental Figs.…”

Section: Discussionsupporting

confidence: 69%

The Role of Nitric Oxide and GluR1 in Presynaptic and Postsynaptic Components of Neocortical Potentiation

2006

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In this study, we investigated the mechanisms underlying synaptic plasticity at the layer IV to II/III pathway in barrel cortex of mice aged 6 -13 weeks. This pathway is one of the likely candidates for expression of experience-dependent plasticity in the barrel cortex and may serve as a model for other IV to II/III synapses in the neocortex. We found that postsynaptic autocamtide-2-inhibitory peptide is sufficient to block long-term potentiation (LTP) (IC 50 of 500 nM), implicating postsynaptic calcium/calmodulin-dependent kinase II in LTP induction. AMPA receptor subunit 1 (GluR1) knock-out mice also showed LTP in this pathway, but potentiation was predominantly presynaptic in origin as determined by paired-pulse analysis, coefficient of variation analysis, and quantal analysis, whereas wild types showed a mixed presynaptic and postsynaptic locus. Quantal analysis at this synapse was validated by measuring uniquantal events in the presence of strontium. The predominantly presynaptic LTP in the GluR1 knock-outs was blocked by postsynaptic antagonism of nitric oxide synthase (NOS), either with intracellular N--nitro-L-arginine methyl ester or N-nitro-L-arginine, providing the first evidence for a retrograde transmitter role for NO at this synapse. Antagonism of NOS in wild types significantly reduced but did not eliminate LTP (group average reduction of 50%). The residual LTP formed a variable proportion of the total LTP in each cell and was found to be postsynaptic in origin. We found no evidence for silent synapses in this pathway at this age. Finally, application of NO via a donor induced potentiation in layer II/III cells and caused an increase in frequency but not amplitude of miniature EPSPs, again implicating NO in presynaptic plasticity.

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Section: Discussionsupporting

confidence: 69%

The Role of Nitric Oxide and GluR1 in Presynaptic and Postsynaptic Components of Neocortical Potentiation

2006

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“…However, variations in quantal size represent a second major contributing factor (21). For instance, variability in EPSC size in hippocampal neurons is to a large degree due to variations in the glutamate concentration reached in the synaptic cleft (35), although quantal variance appears to undergo developmental down-regulation at some CNS synapses (36). Even though several factors, such as the site of release, may play a role in such effects, the present study shows that vesicular content at glutamatergic synapses is variable and therefore a potential control point in presynaptic plasticity.…”

Section: Discussionmentioning

confidence: 76%

An essential role for vesicular glutamate transporter 1 (VGLUT1) in postnatal development and control of quantal size

Wojcik

Rhee

Herzog

et al. 2004

Proc. Natl. Acad. Sci. U.S.A.

443

447

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Quantal neurotransmitter release at excitatory synapses depends on glutamate import into synaptic vesicles by vesicular glutamate transporters (VGLUTs). Of the three known transporters, VGLUT1 and VGLUT2 are expressed prominently in the adult brain, but during the first two weeks of postnatal development, VGLUT2 expression predominates. Targeted deletion of VGLUT1 in mice causes lethality in the third postnatal week. Glutamatergic neurotransmission is drastically reduced in neurons from VGLUT1-deficient mice, with a specific reduction in quantal size. The remaining activity correlates with the expression of VGLUT2. This reduction in glutamatergic neurotransmission can be rescued and enhanced with overexpression of VGLUT1. These results show that the expression level of VGLUTs determines the amount of glutamate that is loaded into vesicles and released and thereby regulates the efficacy of neurotransmission.

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“…At vertebrate neuromuscular junctions, the quantum may be equated with spontaneous signals obtained in the absence of presynaptic action potentials, called miniature currents (or potentials) and believed to be due to release of one neurotransmitter vesicle. For central synapses, this issue remains an open question, as large miniature currents are suggested to arise from the concerted release of several presynaptic vesicles and to be the sum of several quanta [2][3][4][5] . Such multivesicular miniature events could reflect tetrodotoxinresistant action potentials in presynaptic terminals 6 .…”

mentioning

confidence: 99%

Presynaptic calcium stores underlie large-amplitude miniature IPSCs and spontaneous calcium transients

et al. 2000

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articlesThe building block of synaptic transmission is the quantum, the minimal increment of postsynaptic signals 1 . At vertebrate neuromuscular junctions, the quantum may be equated with spontaneous signals obtained in the absence of presynaptic action potentials, called miniature currents (or potentials) and believed to be due to release of one neurotransmitter vesicle. For central synapses, this issue remains an open question, as large miniature currents are suggested to arise from the concerted release of several presynaptic vesicles and to be the sum of several quanta 2-5 . Such multivesicular miniature events could reflect tetrodotoxinresistant action potentials in presynaptic terminals 6 . Another explanation comes from evidence for functional intracellular Ca 2+ stores in presynaptic terminals. First, inositoltrisphosphate (InsP 3 ) receptors are immunolocalized in presynaptic terminals of the deep cerebellar nuclei and retina 7,8 . Second, at the frog neuromuscular junction, agents that affect ryanodine-sensitive Ca 2+ stores also regulate presynaptic intracellular Ca 2+ (Ca 2+ i ) rises and acetylcholine release during high-frequency stimulation 9,10 . Third, action-potential-evoked release of acetylcholine at synapses in Aplysia buccal ganglia is inhibited by ryanodine and augmented by presynaptic injection of cyclic ADP ribose 11 . Fourth, caffeine and/or ryanodine modify presynaptic Ca 2+ i signals in autonomic ganglia 12,13 and in photoreceptors 14 . Finally, in hippocampal pyramidal cells, caffeine or thapsigargin can increase the frequency of miniature IPSCs 15 . Hence, spontaneous Ca 2+ release from presynaptic Ca 2+ stores may provide the synchronization mechanism that leads to multivesicular miniatures. However, except for one study that gave negative results in cultured retinal amacrine cells 16 , this possibility has not been tested systematically.To assess the contribution of intracellular Ca 2+ stores to neurotransmitter release, we monitored the amplitude distribution of miniature synaptic currents while manipulating potential presynaptic Ca 2+ stores. Using cerebellar interneuron-Purkinje cell synapses, in which large miniature synaptic currents are prominent, we found that the largest mIPSCs result from multivesicular release and depend on Ca 2+ mobilization from ryanodine-sensitive presynaptic stores. Further, two-photon confocal microscopy showed ryanodine-sensitive intracellular Ca 2+ i transients highly localized to presumed release sites, which may underlie large miniature currents. RESULTSMiniature IPSCs recorded in cerebellar Purkinje cells, at -60 mV under symmetrical Cl -concentrations and in the presence of tetrodotoxin (TTX) and ionotropic glutamate receptor blockers, showed mean amplitudes of 125 ± 9 pA (n = 28 cells), larger than for most neurons (Fig. 1a). Amplitude histograms had a distinct peak for values less than 200 pA, followed by a long tail with amplitudes up to 1500 pA (Fig. 1b). Spurious summation of independent events did not contribute to the generation of lar...

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Development of the quantal properties of evoked and spontaneous synaptic currents at a brain synapse

Cited by 76 publications

References 46 publications

The Role of Nitric Oxide and GluR1 in Presynaptic and Postsynaptic Components of Neocortical Potentiation

The Role of Nitric Oxide and GluR1 in Presynaptic and Postsynaptic Components of Neocortical Potentiation

An essential role for vesicular glutamate transporter 1 (VGLUT1) in postnatal development and control of quantal size

Presynaptic calcium stores underlie large-amplitude miniature IPSCs and spontaneous calcium transients

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