scholarly journals The basis of sharp spike onset in standard biophysical models

2016 ◽  
Author(s):  
Maria Telenczuk ◽  
Bertrand Fontaine ◽  
Romain Brette
Keyword(s):  
Initial Segment ◽  
Compartment Model ◽  
Coupling Model ◽  
Initiation Site ◽  
Current Loop ◽  
Electrical Dipole ◽  
Biophysical Models ◽  
Axonal Initial Segment ◽  
Spike Initiation ◽  
As If

AbstractIn 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 orthodromic spikes do no 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.Author summaryIn most vertebrate neurons, spikes are initiated in the axonal initial segment, next to the soma. When recorded at the soma, action potentials appear to suddenly rise as if all sodium channels opened at once. This has been previously attributed to the backpropagation of spikes from the initial segment to the soma. Here we demonstrate with biophysical models that backpropagation does not contribute to the sharpness of spike onset. Instead, we show that the phenomenon is due to the resistive coupling between the large somatodendritic compartment and the small axonal compartment, a geometrical discontinuity that leads to an abrupt variation in voltage.

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

2020 ◽  
Vol 16 (7) ◽  
pp. e1008087
Author(s):  
Christophe Verbist ◽  
Michael G. Müller ◽  
Huibert D. Mansvelder ◽  
Robert Legenstein ◽  
Michele Giugliano
Keyword(s):  
Initial Segment ◽  
Axon Initial Segment ◽  
Spike Initiation

scholarly journals Ca2+ entry through NaV channels generates submillisecond axonal Ca2+ signaling

eLife ◽  
2020 ◽  
Vol 9 ◽  
Author(s):  
Naomi AK Hanemaaijer ◽  
Marko A Popovic ◽  
Xante Wilders ◽  
Sara Grasman ◽  
Oriol Pavón Arocas ◽  
...  
Keyword(s):  
Calcium Channels ◽  
High Speed ◽  
Initial Segment ◽  
Hek 293 ◽  
Voltage Gated ◽  
Voltage Gated Calcium Channels ◽  
293 Cells ◽  
Axonal Initial Segment ◽  
Nav Channels ◽  
Activity Dependent

Calcium ions (Ca2+) are essential for many cellular signaling mechanisms and enter the cytosol mostly through voltage-gated calcium channels. Here, using high-speed Ca2+ imaging up to 20 kHz in the rat layer five pyramidal neuron axon we found that activity-dependent intracellular calcium concentration ([Ca2+]i) in the axonal initial segment was only partially dependent on voltage-gated calcium channels. Instead, [Ca2+]i changes were sensitive to the specific voltage-gated sodium (NaV) channel blocker tetrodotoxin. Consistent with the conjecture that Ca2+ enters through the NaV channel pore, the optically resolved ICa in the axon initial segment overlapped with the activation kinetics of NaV channels and heterologous expression of NaV1.2 in HEK-293 cells revealed a tetrodotoxin-sensitive [Ca2+]i rise. Finally, computational simulations predicted that axonal [Ca2+]i transients reflect a 0.4% Ca2+ conductivity of NaV channels. The findings indicate that Ca2+ permeation through NaV channels provides a submillisecond rapid entry route in NaV-enriched domains of mammalian axons.

scholarly journals Altered action potential waveform and shorter axonal initial segment in hiPSC-derived motor neurons with mutations in VRK1

2022 ◽  
pp. 105609
Author(s):  
Rémi Bos ◽  
Khalil Rihan ◽  
Patrice Quintana ◽  
Lara El-Bazzal ◽  
Nathalie Bernard-Marissal ◽  
...  
Keyword(s):  
Action Potential ◽  
Motor Neurons ◽  
Initial Segment ◽  
Axonal Initial Segment ◽  
Action Potential Waveform ◽  
Potential Waveform

scholarly journals Developmental formation of a diffusion barrier in the plasma membrane of the axonal initial segment : single lipid molecule approach

2000 ◽  
Vol 40 (supplement) ◽  
pp. S212
Author(s):  
C. Nakada ◽  
M. Nozaki ◽  
H. Yamashita ◽  
K. Yamaguchi ◽  
Ken Ritchie ◽  
...  
Keyword(s):  
Plasma Membrane ◽  
Diffusion Barrier ◽  
Initial Segment ◽  
Lipid Molecule ◽  
Axonal Initial Segment

Multiple Modes of Action Potential Initiation and Propagation in Mitral Cell Primary Dendrite

2002 ◽  
Vol 88 (5) ◽  
pp. 2755-2764 ◽  
Author(s):  
Wei R. Chen ◽  
Gongyu Y. Shen ◽  
Gordon M. Shepherd ◽  
Michael L. Hines ◽  
Jens Midtgaard
Keyword(s):  
Action Potential ◽  
Primary Dendrite ◽  
Back Propagation ◽  
Olfactory Nerve ◽  
Mitral Cell ◽  
Initiation Site ◽  
Initiation And Propagation ◽  
Action Potential Initiation ◽  
Dendritic Spike ◽  
Spike Initiation

The mitral cell primary dendrite plays an important role in transmitting distal olfactory nerve input from olfactory glomerulus to the soma-axon initial segment. To understand how dendritic active properties are involved in this transmission, we have combined dual soma and dendritic patch recordings with computational modeling to analyze action-potential initiation and propagation in the primary dendrite. In response to depolarizing current injection or distal olfactory nerve input, fast Na+ action potentials were recorded along the entire length of the primary dendritic trunk. With weak-to-moderate olfactory nerve input, an action potential was initiated near the soma and then back-propagated into the primary dendrite. As olfactory nerve input increased, the initiation site suddenly shifted to the distal primary dendrite. Multi-compartmental modeling indicated that this abrupt shift of the spike-initiation site reflected an independent thresholding mechanism in the distal dendrite. When strong olfactory nerve excitation was paired with strong inhibition to the mitral cell basal secondary dendrites, a small fast prepotential was recorded at the soma, which indicated that an action potential was initiated in the distal primary dendrite but failed to propagate to the soma. As the inhibition became weaker, a “double-spike” was often observed at the dendritic recording site, corresponding to a single action potential at the soma. Simulation demonstrated that, in the course of forward propagation of the first dendritic spike, the action potential suddenly jumps from the middle of the dendrite to the axonal spike-initiation site, leaving the proximal part of primary dendrite unexcited by this initial dendritic spike. As Na+conductances in the proximal dendrite are not activated, they become available to support the back-propagation of the evoked somatic action potential to produce the second dendritic spike. In summary, the balance of spatially distributed excitatory and inhibitory inputs can dynamically switch the mitral cell firing among four different modes: axo-somatic initiation with back-propagation, dendritic initiation either with no forward propagation, forward propagation alone, or forward propagation followed by back-propagation.

scholarly journals Contribution of the axon initial segment to action potentials recorded extracellularly

2018 ◽  
Author(s):  
Maria Teleńczuk ◽  
Romain Brette ◽  
Alain Destexhe ◽  
Bartosz Teleńczuk
Keyword(s):  
Action Potential ◽  
Electric Fields ◽  
Action Potentials ◽  
Initial Segment ◽  
Initiation Site ◽  
Axon Initial Segment ◽  
Neuron Activity ◽  
Classical Models ◽  
The Brain

AbstractAction potentials (APs) are electric phenomena that are recorded both intracellularly and extracellularly. APs are usually initiated in the short segment of the axon called the axon initial segment (AIS). It was recently proposed that at onset of an AP the soma and the AIS form a dipole. We study the extracellular signature (the extracellular action potential, EAP) generated by such a dipole. First, we demonstrate the formation of the dipole and its extracellular signature in detailed morphological models of a reconstructed pyramidal neuron. Then, we study the EAP waveform and its spatial dependence in models with axonal AP initiation and contrast it with the EAP obtained in models with somatic AP initiation. We show that in the models with axonal AP initiation the dipole forms between somatodendritic compartments and the AIS, and not between soma and dendrites as in the classical models. Soma-dendrites dipole is present only in models with somatic AP initiation. Our study has consequences for interpreting extracellular recordings of single-neuron activity and determining electrophysiological neuron types, but also for better understanding the origins of the high-frequency macroscopic electric fields recorded in the brain.New & NoteworthyWe studied the consequences of the action potential (AP) initiation site on the extracellular signatures of APs. We show that: (1) at the time of AP initiation the action initial segment (AIS) forms a dipole with the soma, (2) the width but not (3) amplitude of the extracellular AP generated by this dipole increases with the soma-AIS distance. This may help to monitor dynamic changes in the AIS position in experimental in vivo recordings.

Phase Relationships Between Segmentally Organized Oscillators in the Leech Heartbeat Pattern Generating Network

2002 ◽  
Vol 87 (3) ◽  
pp. 1572-1585 ◽  
Author(s):  
Mark A. Masino ◽  
Ronald L. Calabrese
Keyword(s):  
Spike Activity ◽  
Motor Pattern ◽  
Initiation Site ◽  
Pattern Generator ◽  
Primary Site ◽  
Secondary Site ◽  
Cycle Period ◽  
Spike Initiation ◽  
Phase Relationships ◽  
Phase Differences

Motor pattern generating networks that produce segmentally distributed motor outflow are often portrayed as a series of coupled segmental oscillators that produce a regular progression (constant phase differences) in their rhythmic activity. The leech heartbeat central pattern generator is paced by a core timing network, which consists of two coupled segmental oscillators in segmental ganglia 3 and 4. The segmental oscillators comprise paired mutually inhibitory oscillator interneurons and the processes of intersegmental coordinating interneurons. As a first step in understanding the coordination of segmental motor outflow by this pattern generator, we describe the functional synaptic interactions, and activity and phase relationships of the heart interneurons of the timing network, in isolated nerve cord preparations. In the timing network, most (∼75%) of the coordinating interneuron action potentials were generated at a primary spike initiation site located in ganglion 4 (G4). A secondary spike initiation site in ganglion 3 (G3) became active in the absence of activity at the primary site. Generally, the secondary site was characterized by a reluctance to burst and a lower spike frequency, when compared with the primary site. Oscillator interneurons in G3 inhibited spike activity at both initiation sites, whereas oscillator interneurons in G4 inhibited spike activity only at the primary initiation site. This asymmetry in the control of spike activity in the coordinating interneurons may account for the observation that the phase of the coordinating interneurons is more tightly linked to the G3 than G4 oscillator interneurons. The cycle period of the timing network and the phase difference between the ipsilateral G3 and G4 oscillator interneurons were regular within individual preparations, but varied among preparations. This variation in phase differences observed across preparations implies that modulated intrinsic membrane and synaptic properties, rather than the pattern of synaptic connections, are instrumental in determining phase within the timing network.

Multiple Sites of Spike Initiation in a Bifurcating Locust Neurone

1978 ◽  
Vol 76 (1) ◽  
pp. 63-84 ◽  
Author(s):  
W. J. HEITLER ◽  
COREY S. GOODMAN
Keyword(s):  
Action Potential ◽  
Branch Point ◽  
Peripheral Nerves ◽  
Action Potentials ◽  
Room Temperature ◽  
Initiation Site ◽  
Left And Right ◽  
Axon Branch ◽  
Spike Initiation ◽  
Dorsal Unpaired Median

Recordings were made from the metathoracic dorsal unpaired median neurone to the extensor tibiae muscle (DUMETi) in the locust. This is a bifurcating neurone with axons exiting both sideS of the ganglion, whose soma can support a full action potential. Four different spike types were recorded in the soma, each of which we associate with a different region of the neurone. These were (1) a soma (S) spike of 70-90 mV, (2) a neurite (N) spike of 20-40 mV, occurring between the axon hillock and axon branch point, (3) and (4) axon (A) spikes of 8–15 mV, occurring distal to the branch point on the left and right axons. Each of these regions must therefore have its own spike initiation site. At spike frequencies greater than about 10 Hz at room temperature or 1-5 Hz at 32 °C (the preferred environmental temperature of the locust) the S-spike may fail, revealing A-spikes, or more rarely N-spikes. A-spikes usually consist of two more-or-less separate components, Al and Ar, which can be correlated with action potentials in the left and right axon branches by recording spikes extracellularly in the peripheral nerves on each side. Occasionally single component A-spikes occur when an action potential is initiated in only one axon, and fails to propagate across the branch point to the contralateral axon. Thus, action potentials may occur independently in the branches of this bifurcating neurone. After unilateral axotomy only S-spikes and N-spikes are recorded, indicating that action potentials no longer fail to propagate across the branch point. Anatomical asymmetries in the axon branches of DUMETi have been correlated with physiological asymmetries recorded in the soma of the same neurone.

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