Analog modulation of spike‐evoked transmission in <scp>CA</scp>3 circuits is determined by axonal <scp>K</scp>v1.1 channels in a time‐dependent manner

Bialowas, Andrzej; Rama, Sylvain; Zbili, Mickaël; Marra, Vincenzo; Fronzaroli-Molinières, Laure; Ankri, Norbert; Carlier, Edmond; Debanne, Dominique

doi:10.1111/ejn.12787

Cited by 30 publications

(78 citation statements)

References 44 publications

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“…For example, the kinetics of the analogdigital enhancement are slow and fit well with the inactivation kinetics of I D ( [4,24,42]). In fact, no ADF is observed with brief analog depolarization (~100-200 ms) and ADF appears only after several seconds of presynaptic depolarization.…”

Section: Adf Resulting From Inactivation Of Presynaptic Kv1 Channelsmentioning

confidence: 72%

“…Hybrid analog-digital enhancement of synaptic transmission at spiking synapses initially described in invertebrates [29,37,39,40] has been more recently reported in many mammalian synapses of the CNS including cortical [24,42,48], cerebellar [9,12], and hippocampal excitatory synapses ( [1,18,34]; Bialowas et al, 2014). In these examples, synaptic transmission evoked by single APs is enhanced as the result of analog-mediated depolarization (10-30 mV) of the presynaptic element for a few tens to hundreds of milliseconds (Fig.…”

Section: Analog-digital Signaling: Analog Signaling At Spiking Synapsesmentioning

confidence: 93%

“…In hippocampal dentate granule cell axons (mossy fibers), the combination of analog depolarization spreading from the soma in the form of an excitatory presynaptic potential (EPreSP) and digital signaling in the form of an AP, enhances glutamatergic transmission at the mossy fiber-CA3 cell synapse [1]. For local connections such as these that occur over relatively short distances between L5 pyramidal neurons in the neocortex, hippocampal CA3 pyramidal neurons or GABAergic interneurons in the cerebellum, the analog-mediated component of the facilitation of synaptic transmission is on average 1-2% per mV of somatic depolarization ( [12,24,42]; Bialowas et al, 2014).…”

Section: Analog-digital Signaling: Analog Signaling At Spiking Synapsesmentioning

confidence: 99%

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Modulation of spike-evoked synaptic transmission: The role of presynaptic calcium and potassium channels

Rama

Zbili

Debanne

2015

Biochimica et Biophysica Acta (BBA) - Molecular Cell Research

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Action potentials are usually considered as the smallest unit of neuronal information conveyed by presynaptic neurons to their postsynaptic target. Thus, neuronal signaling in brain circuits is all-or-none or digital. However, recent studies indicate that subthreshold analog variation in presynaptic membrane potential modulates spike-evoked transmission. The informational content of each presynaptic action potential is therefore greater than initially expected. This property constitutes a form of fast activity-dependent modulation of functional coupling. Therefore, it could have important consequences on information processing in neural networks in parallel with more classical forms of presynaptic short-term facilitation based on repetitive stimulation, modulation of presynaptic calcium or modifications of the release machinery. We discuss here how analog voltage shift in the presynaptic neuron may regulate spike-evoked release of neurotransmitter through the modulation of voltage-gated calcium and potassium channels in the axon and presynaptic terminal. This article is part of a Special Issue entitled: 13th European Symposium on Calcium.

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Section: Adf Resulting From Inactivation Of Presynaptic Kv1 Channelsmentioning

confidence: 72%

Section: Analog-digital Signaling: Analog Signaling At Spiking Synapsesmentioning

confidence: 93%

Section: Analog-digital Signaling: Analog Signaling At Spiking Synapsesmentioning

confidence: 99%

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Modulation of spike-evoked synaptic transmission: The role of presynaptic calcium and potassium channels

Rama

Zbili

Debanne

2015

Biochimica et Biophysica Acta (BBA) - Molecular Cell Research

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“…Pharmacological blockade of Kv1 channels leads to an increase of the spike duration and Ca 2+ entry in CA3 presynaptic terminals (26). We therefore asked whether a loss of axonal Kv1 channels resulting from LGI1 deficiency might lead to increased glutamate release, by comparing the effects of DTX-K on both spontaneous and spike-evoked excitatory postsynaptic currents (EPSCs) from WT vs. Lgi1-null CA3 neurons.…”

Section: Boillot Et Al Recently Reported Thatmentioning

confidence: 99%

LGI1 tunes intrinsic excitability by regulating the density of axonal Kv1 channels

Seagar

Russier

Caillard

et al. 2017

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

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105

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Autosomal dominant epilepsy with auditory features results from mutations in leucine-rich glioma-inactivated 1 (LGI1), a soluble glycoprotein secreted by neurons. Animal models of LGI1 depletion display spontaneous seizures, however, the function of LGI1 and the mechanisms by which deficiency leads to epilepsy are unknown. We investigated the effects of pure recombinant LGI1 and genetic depletion on intrinsic excitability, in the absence of synaptic input, in hippocampal CA3 neurons, a classical focus for epileptogenesis. Our data indicate that LGI1 is expressed at the axonal initial segment and regulates action potential firing by setting the density of the axonal Kv1.1 channels that underlie dendrotoxin-sensitive D-type potassium current.LGI1 deficiency incurs a >50% down-regulation of the expression of Kv1.1 and Kv1.2 via a posttranscriptional mechanism, resulting in a reduction in the capacity of axonal D-type current to limit glutamate release, thus contributing to epileptogenesis.LGI1 | Kv1 channels | D-type current | intrinsic excitability | epilepsy

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“…Inactivation of axonal Kv1-family channels contributes to "analog" signaling by broadening presynaptic action potentials (6)(7)(8)(9). Investigations of presynaptic spike shape in small presynaptic boutons have relied heavily on extrapolation from recordings in blebs that form after axons have been transected (2,6,8,9).…”

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confidence: 99%

Kv1.1 channelopathy abolishes presynaptic spike width modulation by subthreshold somatic depolarization

Vivekananda

Novák

Bello

et al. 2017

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

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Although action potentials propagate along axons in an all-or-none manner, subthreshold membrane potential fluctuations at the soma affect neurotransmitter release from synaptic boutons. An important mechanism underlying analog-digital modulation is depolarizationmediated inactivation of presynaptic Kv1-family potassium channels, leading to action potential broadening and increased calcium influx. Previous studies have relied heavily on recordings from blebs formed after axon transection, which may exaggerate the passive propagation of somatic depolarization. We recorded instead from small boutons supplied by intact axons identified with scanning ion conductance microscopy in primary hippocampal cultures and asked how distinct potassium channels interact in determining the basal spike width and its modulation by subthreshold somatic depolarization. Pharmacological or genetic deletion of Kv1.1 broadened presynaptic spikes without preventing further prolongation by brief depolarizing somatic prepulses. A heterozygous mouse model of episodic ataxia type 1 harboring a dominant Kv1.1 mutation had a similar broadening effect on basal spike shape as deletion of Kv1.1; however, spike modulation by somatic prepulses was abolished. These results argue that the Kv1.1 subunit is not necessary for subthreshold modulation of spike width. However, a disease-associated mutant subunit prevents the interplay of analog and digital transmission, possibly by disrupting the normal stoichiometry of presynaptic potassium channels.channelopathy | synaptic transmission | potassium channel A lthough action potentials are generated at the axon initial segment in an all-or-none manner, synaptic transmission can be modulated by electrotonic propagation of subthreshold membrane depolarization from the soma (1-6). Inactivation of axonal Kv1-family channels contributes to "analog" signaling by broadening presynaptic action potentials (6-9). Investigations of presynaptic spike shape in small presynaptic boutons have relied heavily on extrapolation from recordings in blebs that form after axons have been transected (2,6,8,9). A potential pitfall of this method is that the ion channels present in blebs may not be representative of the normal complement of channels at an unperturbed bouton. A further difficulty is that the attenuation of voltage with distance from the soma is likely to be smaller than when recording from an intact axon. Indeed, classical cable theory predicts that steady-state somatic voltage should decrease by ∼63% at one length constant if the axon is represented by an infinite cable, but only by ∼35% if it is sealed at the same point (10). The discrepancy increases as the axon is made shorter: if the axon is cut at half a length constant, the attenuation of steady-state voltage at its termination is only ∼29% of that predicted for an infinite cable. Given that the length constant of unmyelinated axons in the CNS has been estimated in the range of 400-600 μm (1-3, 9, 11), this implies that the modulation of action potential shape...

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Analog modulation of spike‐evoked transmission in CA3 circuits is determined by axonal Kv1.1 channels in a time‐dependent manner

Cited by 30 publications

References 44 publications

Modulation of spike-evoked synaptic transmission: The role of presynaptic calcium and potassium channels

Modulation of spike-evoked synaptic transmission: The role of presynaptic calcium and potassium channels

LGI1 tunes intrinsic excitability by regulating the density of axonal Kv1 channels

Kv1.1 channelopathy abolishes presynaptic spike width modulation by subthreshold somatic depolarization

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