Action potential initiation in a multi-compartmental model with cooperatively gating Na channels in the axon initial segment

Öz, Pınar; Huang, Min; Wolf, Fred

doi:10.1007/s10827-015-0561-9

“…Cooperative activation has been demonstrated in calcium [27,28], potassium [29] and HCN channels [30], and in pharmacologically altered Na channels of cardiac myocytes [31]. It should appear in AIS phase plots as a very large increase in dV/dt at spike initiation [5], with a biphasic phase plot if only part of the channels (e.g. the Nav1.6 subtype) cooperate [32].…”

Section: Discussionmentioning

confidence: 99%

“…It has been proposed that Na channels in the AIS cooperate, so that they actually open all at once instead of gradually as a function of local voltage [3,5]. However, this phenomenon has not been observed in the AIS (see Discussion).…”

Section: Introductionmentioning

confidence: 98%

The basis of sharp spike onset in standard biophysical models

Teleńczuk

¹

,

Fontaine

²

,

Brette

³

2017

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In most vertebrate neurons, spikes initiate in the axonal initial segment (AIS). When recorded in the soma, they have a surprisingly sharp onset, as if sodium (Na) channels opened abruptly. The main view stipulates that spikes initiate in a conventional manner at the distal end of the AIS, then progressively sharpen as they backpropagate to the soma. We examined the biophysical models used to substantiate this view, and we found that spikes do not initiate through a local axonal current loop that propagates along the axon, but through a global current loop encompassing the AIS and soma, which forms an electrical dipole. Therefore, the phenomenon is not adequately modeled as the backpropagation of an electrical wave along the axon, since the wavelength would be as large as the entire system. Instead, in these models, we found that spike initiation rather follows the critical resistive coupling model proposed recently, where the Na current entering the AIS is matched by the axial resistive current flowing to the soma. Besides demonstrating it by examining the balance of currents at spike initiation, we show that the observed increase in spike sharpness along the axon is artifactual and disappears when an appropriate measure of rapidness is used; instead, somatic onset rapidness can be predicted from spike shape at initiation site. Finally, we reproduce the phenomenon in a two-compartment model, showing that it does not rely on propagation. In these models, the sharp onset of somatic spikes is therefore not an artifact of observing spikes at the incorrect location, but rather the signature that spikes are initiated through a global soma-AIS current loop forming an electrical dipole.

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“…1B, bottom, human cortical pyramidal neuron from Testa--Silva et al, 2014), as if all Na channels opened at once. It has been proposed that Na channels in the AIS cooperate, so that they actually open all at once instead of gradually as a function of local voltage (Naundorf et al, 2006;Öz et al, 2015). However, this phenomenon has not been observed in the AIS (see Discussion).…”

Section: Introductionmentioning

confidence: 95%

“…It has been proposed that Na channels in the AIS cooperate, so that they actually open all at once 56 instead of gradually as a function of local voltage (Naundorf et al, 2006;Öz et al, 2015).…”

mentioning

confidence: 99%

The basis of sharp spike onset in standard biophysical models

Teleńczuk

¹

,

Fontaine

²

,

Brette

³

2016

Preprint

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In most vertebrate neurons, spikes initiate in the axonal initial segment (AIS). When recorded in the soma, they have a surprisingly sharp onset, as if sodium (Na) channels opened abruptly. The main view stipulates that spikes initiate in a conventional manner at the distal end of the AIS, then progressively sharpen as they backpropagate to the soma. We examined the biophysical models used to substantiate this view, and we found that spikes do not initiate through a local axonal current loop that propagates along the axon, but through a global current loop encompassing the AIS and soma, which forms an electrical dipole. Therefore, the phenomenon is not adequately modeled as the backpropagation of an electrical wave along the axon, since the wavelength would be as large as the entire system. Instead, in these models, we found that spike initiation rather follows the critical resistive coupling model proposed recently, where the Na current entering the AIS is matched by the axial resistive current flowing to the soma. Besides demonstrating it by examining the balance of currents at spike initiation, we show that the observed increase in spike sharpness along the axon is artifactual and disappears when an appropriate measure of rapidness is used; instead, somatic onset rapidness can be predicted from spike shape at initiation site. Finally, we reproduce the phenomenon in a two-compartment model, showing that it does not rely on propagation. In these models, the sharp onset of somatic spikes is therefore not an artifact of observing spikes at the incorrect location, but rather the signature that spikes are initiated through a global soma-AIS current loop forming an electrical dipole.

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“…The proposed biophysical bases, underlying rapid APs, have thus been linked to ion channel cooperativity [1,15], axo-somatic backpropagation [13], and to the electrotonic coupling of dendro-somatic compartments to the site of AP initiation in the axon [10,11]. Recently, Brette and collaborators further explored how the specific location of the AP initiation in the axon (i.e.…”

Section: Introductionmentioning

confidence: 99%

The location of the axon initial segment affects the bandwidth of spike initiation dynamics

Verbist

¹

,

Müller

²

,

Mansvelder

³

et al. 2020

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The dynamics and the sharp onset of action potential (AP) generation have recently been the subject of intense experimental and theoretical investigations. According to the resistive coupling theory, an electrotonic interplay between the site of AP initiation in the axon and the somato-dendritic load determines the AP waveform. This phenomenon not only alters the shape of APs recorded at the soma, but also determines the dynamics of excitability across a variety of time scales. Supporting this statement, here we generalize a previous numerical study and extend it to the quantification of the input-output gain of the neuronal dynamical response. We consider three classes of multicompartmental mathematical models, ranging from ball-and-stick simplified descriptions of neuronal excitability to 3D-reconstructed biophysical models of excitatory neurons of rodent and human cortical tissue. For each model, we demonstrate that increasing the distance between the axonal site of AP initiation and the soma markedly increases the bandwidth of neuronal response properties. We finally consider the Liquid State Machine paradigm, exploring the impact of altering the site of AP initiation at the level of a neuronal population, and demonstrate that an optimal distance exists to boost the computational performance of the network in a simple classification task.

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Action potential initiation in a multi-compartmental model with cooperatively gating Na channels in the axon initial segment

Cited by 11 publications

References 56 publications

The basis of sharp spike onset in standard biophysical models

The basis of sharp spike onset in standard biophysical models

The basis of sharp spike onset in standard biophysical models

The location of the axon initial segment affects the bandwidth of spike initiation dynamics

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