Preserving axosomatic spiking features despite diverse dendritic morphology

Hay, Etay; Schürmann, Felix; Markram, Henry; Segev, Idan

doi:10.1152/jn.00048.2013

Cited by 66 publications

(74 citation statements)

References 57 publications

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“…Therefore, the changes in the dendritic surface can strongly modulate the AP onset rapidness at AIS. This recent findings were also suggested or implied in some of the previous experimental and theoretical studies (Bekkers and Hauser 2007;Hay et al 2013;Mainen et al 1995). Although the contribution of dendritic load on the AP initiation and onset at AIS wasn't included in CAIS model, this study presents important findings that should be further studied.…”

Section: Discussionsupporting

confidence: 74%

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

2015

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Somatic action potentials (AP) of cortical pyramidal neurons have characteristically high onset-rapidness. The onset of the AP waveform is an indirect measure for the ability of a neuron to respond to temporally fast-changing stimuli. Theoretical studies on the pyramidal neuron response usually involves a canonical Hodgkin-Huxley (HH) type ion channel gating model, which assumes statistically independent gating of each individual channel. However, cooperative activity of ion channels are observed for various cell types, meaning that the activity (e.g. opening) of one channel triggers the activity (e.g. opening) of a certain fraction of its neighbors and hence, these groups of channels behave as a unit. In this study, we describe a multi-compartmental conductance-based model with cooperatively gating voltage-gated Na channels in the axon initial segment. Our model successfully reproduced the somatic sharp AP onsets of cortical pyramidal neurons. The onset latencies from the initiation site to the soma and the conduction velocities were also in agreement with the previous experimental studies.

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Section: Discussionsupporting

confidence: 74%

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

2015

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“…First, the initiation site is very close to the soma, as previously noted, and axonal diameter is small compared to the soma, especially if the conductance load of the dendritic tree is considered [36]. Thus, biophysical theory predicts that the soma is a current sink for the initiation site [11], i.e., that most Na current entering the AIS flows to the soma, producing a voltage gradient between the two sites.…”

Section: Discussionmentioning

confidence: 99%

The basis of sharp spike onset in standard biophysical models

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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“…Several studies found active sodium and potassium currents in presynaptic terminals [53][54][55][56][57][58]; therefore, terminations were assigned the biophysical properties of nodes of Ranvier [45,59]. The nodes and terminals had the same passive parameters as the initial segment, including a specific capacitance (Cm) of 1 µF/cm 2 and cell-type-specific passive membrane resistance (Rm), while the myelinated sections had an Rm of 1.125 MΩcm 2 [60] and Cm of 0.02 µF/cm 2 [60][61][62].…”

Section: Myelinated Axon Biophysicsmentioning

confidence: 99%

Biophysically Realistic Neuron Models for Simulation of Cortical Stimulation

Aberra

Peterchev

Grill

2018

Preprint

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1.AbstractObjectiveWe implemented computational models of human and rat cortical neurons for simulating the neural response to cortical stimulation with electromagnetic fields.ApproachWe adapted model neurons from the library of Blue Brain models to reflect biophysical and geometric properties of both adult rat and human cortical neurons and coupled the model neurons to exogenous electric fields (E-fields). The models included 3D reconstructed axonal and dendritic arbors, experimentally-validated electrophysiological behaviors, and multiple, morphological variants within cell types. Using these models, we characterized the single-cell responses to intracortical microstimulation (ICMS) and uniform E-field with dc as well as pulsed currents.Main resultsThe strength-duration and current-distance characteristics of the model neurons to ICMS agreed with published experimental results, as did the subthreshold polarization of cell bodies and axon terminals by uniform dc E-fields. For all forms of stimulation, the lowest threshold elements were terminals of the axon collaterals, and the dependence of threshold and polarization on spatial and temporal stimulation parameters was strongly affected by morphological features of the axonal arbor, including myelination, diameter, and branching.SignificanceThese results provide key insights into the mechanisms of cortical stimulation. The presented models can be used to study various cortical stimulation modalities while incorporating detailed spatial and temporal features of the applied E-field.

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Preserving axosomatic spiking features despite diverse dendritic morphology

Cited by 66 publications

References 57 publications

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

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

The basis of sharp spike onset in standard biophysical models

Biophysically Realistic Neuron Models for Simulation of Cortical Stimulation

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