Applicability of the coefficient of variation method for analyzing synaptic plasticity

Faber, Donald S.; Korn, Henri

doi:10.1016/s0006-3495(91)82162-2

Cited by 344 publications

(287 citation statements)

References 16 publications

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“…The coefficient of variation (CV) of EPSP amplitudes ranged from 9% to 86% and was negatively correlated to the number of bouton touches (Fig. 3D), which is in agreement with predictions derived from models of quantal synaptic transmission (34), indicating that bouton touches are indeed correlated with the existence of functional synapses.…”

Section: Resultssupporting

confidence: 87%

The neocortical microcircuit as a tabula rasa

Kalisman

Silberberg

Markram

2005

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

183

139

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The neocortex has a high capacity for plasticity. To understand the full scope of this capacity, it is essential to know how neurons choose particular partners to form synaptic connections. By using multineuron whole-cell recordings and confocal microscopy we found that axons of layer V neocortical pyramidal neurons do not preferentially project toward the dendrites of particular neighboring pyramidal neurons; instead, axons promiscuously touch all neighboring dendrites without any bias. Functional synaptic coupling of a small fraction of these neurons is, however, correlated with the existence of synaptic boutons at existing touch sites. These data provide the first direct experimental evidence for a tabula rasa-like structural matrix between neocortical pyramidal neurons and suggests that pre-and postsynaptic interactions shape the conversion between touches and synapses to form specific functional microcircuits. These data also indicate that the local neocortical microcircuit has the potential to be differently rewired without the need for remodeling axonal or dendritic arbors.connectivity ͉ neocortex ͉ spines A hallmark of the neocortex is its sensitivity to environmental conditions that can drive profound structural and functional changes (1-4). At the microcircuit level, these changes include the creation, elimination, and modification of synaptic connections between neurons (5-10). To understand the mechanisms and full potential of cortical plasticity, it is essential to answer a fundamental question: How does a neuron choose to connect to only a small fraction of its neighboring neurons in a cortical volume packed with intertwined dendrites? This question has been debated extensively for more than a decade (11)(12)(13)(14)(15). At the heart of the debate is the question of whether recurrent synapses between pyramidal neurons, which are the vast majority of neocortical synapses (14, 16), are placed randomly to form an arbitrary functional microcircuit or deterministically to form a highly specific functional microcircuit.Theoretical work suggests that it is essentially impossible for an axon of a pyramidal neuron to avoid touching any other pyramidal neuron within the local microcircuit (up to Ϸ150 m from the soma) (see Fig. 1C) (14,17,18). However, experimental studies with paired recordings clearly indicate that pyramidal neurons are synaptically connected to only a small fraction of their neighboring neurons (19)(20)(21)(22)(23)(24). Even more puzzling is that when a functional connection is established, multiple synaptic contacts are observed (22,23,25,26). Furthermore, there are only enough synaptic boutons on a local pyramidal axon (Ϸ1,000-1,500) to form multiple synaptic contacts with a small fraction of the 1,000-2,000 neighboring pyramidal neurons (14,27). A form of target neuron selection must therefore take place at some level. To resolve this question, we undertook a combined multineuron recording and confocal study to compare structural and functional properties of connections between neocort...

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Section: Resultssupporting

confidence: 87%

The neocortical microcircuit as a tabula rasa

Kalisman

Silberberg

Markram

2005

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

183

139

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“…The stationary periods were 5-10 min before TBS and 15-35 min after TBS, when the peak amplitude of EPSPs was stable. The value of CV Ϫ2 was corrected for the variance of the background noise, using the relation 2 ϭ 2 (measured) Ϫ 2 (noise) (Faber and Korn 1991). To measure the background noise we used 2 ms of traces before stimulus.…”

Section: Methodsmentioning

confidence: 99%

“…To further address the presynaptic and postsynaptic issue, we next made the CV analysis (Faber and Korn, 1991;Sjöström et al, 2003). On the basis of a binomial model of synaptic transmission, functional changes in presynaptic sites are expected to be accompanied by a change in the CV of synaptic responses: the values of CV Ϫ2 that are plotted against the change in efficacy could be on the diagonal line, if the release probability is very low.…”

Section: Expression Of Ltp Of Excitatory Synapses On Fs-gaba Neurons mentioning

confidence: 99%

Metabotropic Glutamate Receptor Type 5-Dependent Long-Term Potentiation of Excitatory Synapses on Fast-Spiking GABAergic Neurons in Mouse Visual Cortex

Sarihi¹,

Jiang²,

Komaki‬³

et al. 2008

J. Neurosci.

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“…assays that are sensitive to changes in presynaptic probability of neurotransmitter release [Pr (25,26)]. PPR, the ratio of the amplitude of the second EPSC to the first EPSC evoked by two stimuli applied in rapid succession (Fig.…”

Section: Znt3-dependent Synaptic Zinc Inhibits Ampar Epscs In Dorsalmentioning

confidence: 99%

AMPA receptor inhibition by synaptically released zinc

Kalappa

Anderson

Goldberg

et al. 2015

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

111

149

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The vast amount of fast excitatory neurotransmission in the mammalian central nervous system is mediated by AMPA-subtype glutamate receptors (AMPARs). As a result, AMPAR-mediated synaptic transmission is implicated in nearly all aspects of brain development, function, and plasticity. Despite the central role of AMPARs in neurobiology, the fine-tuning of synaptic AMPA responses by endogenous modulators remains poorly understood. Here we provide evidence that endogenous zinc, released by single presynaptic action potentials, inhibits synaptic AMPA currents in the dorsal cochlear nucleus (DCN) and hippocampus. Exposure to loud sound reduces presynaptic zinc levels in the DCN and abolishes zinc inhibition, implicating zinc in experience-dependent AMPAR synaptic plasticity. Our results establish zinc as an activity-dependent, endogenous modulator of AMPARs that tunes fast excitatory neurotransmission and plasticity in glutamatergic synapses.AMPA receptors | zinc | ZnT3 | synaptic plasticity | auditory T he development, function, and experience-dependent plasticity of the mammalian brain depend on the refined neuronal interactions that occur in synapses. In the majority of excitatory synapses, the release of the neurotransmitter glutamate from presynaptic neurons opens transmembrane ion channels in postsynaptic neurons, the ionotropic glutamate receptors, thereby generating the flow of excitatory signaling in the brain. As a result, these receptors play a fundamental role in normal function and development of the brain, and they are also involved in many brain disorders (1).The ionotropic glutamate receptor family consists of AMPA, kainate, and NMDA receptors (NMDARs). Although kainate receptor-mediated excitatory postsynaptic responses occur in a few central synapses (2), AMPA receptors (AMPARs) and NMDARs are localized in the postsynaptic density of the vast majority of glutamatergic synapses in the brain, mediating most of excitatory neurotransmission (1). NMDAR function is regulated by a wide spectrum of endogenous allosteric neuromodulators that fine-tune synaptic responses (3-5); however, much less is known about endogenous AMPAR neuromodulators [(1, 5), but see refs. 6 and 7]. Recent structural studies revealed that the amino terminal domain (ATD) and ligand-binding domain (LBD) are tightly packed in NMDARs but not AMPARs (8-10). These structural differences explain some of the functional differences in allosteric modulation between AMPARs and NMDARs, such as why the ATD of NMDARs, unlike that of AMPARs, modulates function and contains numerous binding sites for allosteric regulators. Nonetheless, given the importance of fine-tuning both synaptic AMPAR and NMDAR responses for brain function, it is puzzling that there is not much evidence for endogenous, extracellular AMPAR modulation. The discovery and establishment of endogenous AMPAR modulators is crucial both for understanding ionotropic glutamate receptor signaling and for developing therapeutic agents for the treatment of AMPAR-related disorders, such as d...

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Applicability of the coefficient of variation method for analyzing synaptic plasticity

Cited by 344 publications

References 16 publications

The neocortical microcircuit as a tabula rasa

The neocortical microcircuit as a tabula rasa

Metabotropic Glutamate Receptor Type 5-Dependent Long-Term Potentiation of Excitatory Synapses on Fast-Spiking GABAergic Neurons in Mouse Visual Cortex

AMPA receptor inhibition by synaptically released zinc

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