Spike-Time Precision and Network Synchrony Are Controlled by the Homeostatic Regulation of the D-Type Potassium Current

Cudmore, Robert H.; Fronzaroli-Molinières, Laure; Giraud, Pierre; Debanne, Dominique

doi:10.1523/jneurosci.0740-10.2010

Cited by 99 publications

(140 citation statements)

References 56 publications

(88 reference statements)

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“…S1B). The dendrotoxin-sensitive D-type potassium current contributes to setting intrinsic excitability (24) in many types of neurons. In both control and LGI1-treated cultures, bath application of the selective Kv1.1 antagonist DTX-K reduced the rheobase to a similar baseline value of ∼50 pA (Fig.…”

Section: Exogenousmentioning

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.

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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Section: Exogenousmentioning

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.

105

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“…As in past studies (de la Rocha et al 2007;Shea-Brown et al 2008;Vilela and Lindner 2009;Litwin-Kumar et al 2011), we use a well-established linear approximation to relate y(t) to an input stimulus s(t). To transition from the temporal to frequency domain we define the Fourier transform of the time series…”

Section: Linear Response Theorymentioning

confidence: 99%

“…We show that Kv7 conductances reduce firing rates and spike train correlations. Using a perturbative theoretical framework (de la Rocha et al 2007; Shea- , we relate the reduction in pairwise correlation to how Kv7 conductances shape single-neuron filter properties. The theory shows that the reduction in correlations is beyond that expected from the reduction in firing rates (de la Rocha et al 2007) and involves an active cancellation of correlated inputs.…”

mentioning

confidence: 99%

“…Using a perturbative theoretical framework (de la Rocha et al 2007; Shea- , we relate the reduction in pairwise correlation to how Kv7 conductances shape single-neuron filter properties. The theory shows that the reduction in correlations is beyond that expected from the reduction in firing rates (de la Rocha et al 2007) and involves an active cancellation of correlated inputs. This decoupling of firing rates and correlations by Kv7 conductances prevents synaptic scaling or homeostatic plasticity of passive membrane properties from simultaneously correcting for Kv7 pathology-induced increases in firing rates and correlations.…”

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confidence: 99%

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Kv7 channels regulate pairwise spiking covariability in health and disease

Ocker

Doiron

2014

Journal of Neurophysiology

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Ocker GK, Doiron B. Kv7 channels regulate pairwise spiking covariability in health and disease. J Neurophysiol 112: 340 -352, 2014. First published April 30, 2014 doi:10.1152/jn.00084.2014.-Low-threshold M currents are mediated by the Kv7 family of potassium channels. Kv7 channels are important regulators of spiking activity, having a direct influence on the firing rate, spike time variability, and filter properties of neurons. How Kv7 channels affect the joint spiking activity of populations of neurons is an important and open area of study. Using a combination of computational simulations and analytic calculations, we show that the activation of Kv7 conductances reduces the covariability between spike trains of pairs of neurons driven by common inputs. This reduction is beyond that explained by the lowering of firing rates and involves an active cancellation of common fluctuations in the membrane potentials of the cell pair. Our theory shows that the excess covariance reduction is due to a Kv7-induced shift from low-pass to band-pass filtering of the single neuron spike train response. Dysfunction of Kv7 conductances is related to a number of neurological diseases characterized by both elevated firing rates and increased network-wide correlations. We show how changes in the activation or strength of Kv7 conductances give rise to excess correlations that cannot be compensated for by synaptic scaling or homeostatic modulation of passive membrane properties. In contrast, modulation of Kv7 activation parameters consistent with pharmacological treatments for certain hyperactivity disorders can restore normal firing rates and spiking correlations. Our results provide key insights into how regulation of a ubiquitous potassium channel class can control the coordination of population spiking activity. . M currents have slow activation kinetics, lack inactivation dynamics, and decrease overall cellular excitability (Aiken et al. 1995;Gu et al. 2005;Higgs et al. 2007;Lawrence et al. 2006;Peters et al. 2005). M currents are due to heteromeric channels composed of Kv7.2/3 and Kv7.3/5 subunits that are encoded by the KCNQ gene family (Wang et al. 1998;Selyanko et al. 2001;Peters et al. 2005). Dysfunction of Kv7 channels is related to a number of disease: shifts in Kv7 activation have been associated with tinnitus (Li et al. 2013), mutations involved in peripheral nerve hyperexcitability decrease Kv7 surface expression (Wuttke et al. 2007), and changes in both voltage-sensing and surface expression have been related to neonatal epilepsy (Soldovieri et al. 2006). Kv7 mutations are also associated with the most common childhood epilepsy condition, rolandic epilepsy (Coppola et al. 2003;Neubauer et al. 2008). Despite the evidence of reduced Kv7 activation in tinnitus, chronic pain, and epilepsy, there lacks a coherent mechanistic theory for how Kv7 channels contribute to physiological signatures of such disease states.Two common neural correlates of tinnitus and epilepsy are elevated firing rates and excess spike train synchro...

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“…By lowering the minimal synaptic input required to generate cell firing, LLPIE could contribute to the strengthening of cortical responsiveness observed following repeated coactivation of specific whiskers or behavioral training (Diamond et al, 1994;Wiest et al, 2010). In addition, as shown in hippocampus (Cudmore et al, 2010), the enhanced spike-time precision after LLPIE induction could increase the propensity for synchronization in the cortical network. This persistent increase in firing reliability within the conditioned network might also promote the spread of excitation leading to functional reconfiguration of sensory receptive fields.…”

Section: Functional Implications Of Bidirectional Intrinsic Plasticitymentioning

confidence: 99%

Bidirectional Plasticity of Intrinsic Excitability Controls Sensory Inputs Efficiency in Layer 5 Barrel Cortex Neuronsin Vivo

Mahon

Charpier

2012

J. Neurosci.

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Responsiveness of cortical neurons to sensory inputs can be altered by experience and learning. While synaptic plasticity is generally proposed as the underlying cellular mechanism, possible contributions of activity-dependent changes in intrinsic excitability remain poorly investigated. Here, we show that periods of rhythmic firing in rat barrel cortex layer 5 pyramidal neurons can trigger a long-lasting increase or decrease in their membrane excitability in vivo. Potentiation of cortical excitability consisted of an increased firing in response to intracellular stimulation and a reduction in threshold current for spike initiation. Conversely, depression of cortical excitability was evidenced by an augmented firing threshold leading to a reduced current-evoked spiking. The direction of plasticity depended on the baseline level of spontaneous firing rate and cell excitability. We also found that changes in intrinsic excitability were accompanied by corresponding modifications in the effectiveness of sensory inputs. Potentiation and depression of cortical neuron excitability resulted, respectively, in an increased or decreased firing probability on whisker-evoked synaptic responses, without modifications in the synaptic strength itself. These data suggest that bidirectional intrinsic plasticity could play an important role in experience-dependent refinement of sensory cortical networks.

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Spike-Time Precision and Network Synchrony Are Controlled by the Homeostatic Regulation of the D-Type Potassium Current

Cited by 99 publications

References 56 publications

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

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

Kv7 channels regulate pairwise spiking covariability in health and disease

Bidirectional Plasticity of Intrinsic Excitability Controls Sensory Inputs Efficiency in Layer 5 Barrel Cortex Neuronsin Vivo

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