scholarly journals Spikelets in Pyramidal Neurons: Action Potentials Initiated in the Axon Initial Segment That Do Not Activate the Soma

2017 ◽  
Vol 13 (1) ◽  
pp. e1005237 ◽  
Author(s):  
Martina Michalikova ◽  
Michiel W. H. Remme ◽  
Richard Kempter
Keyword(s):  
Action Potentials ◽  
Initial Segment ◽  
Pyramidal Neurons ◽  
Axon Initial Segment

scholarly journals Optical measurement of physiological sodium currents in the axon initial segment

2020 ◽  
Author(s):  
Luiza Filipis ◽  
Marco Canepari
Keyword(s):  
Temporal Resolution ◽  
Initial Segment ◽  
Pyramidal Neurons ◽  
Optical Measurement ◽  
Brain Slices ◽  
Axon Initial Segment ◽  
Neuron Models ◽  
Pixel Resolution ◽  
Fluorescence Measurements ◽  
Kinetics Of

ABSTRACTIn most neurons of the mammalian central nervous system, the action potential (AP) is triggered in the axon initial segment (AIS) by a fast Na+ current mediated by voltage-gated Na+ channels. The intracellular Na+ increase associated with the AP has been measured using fluorescent Na+ indicators, but with insufficient resolution to resolve the Na+ current in the AIS. In this article, we report the critical improvement in temporal resolution of the Na+ imaging technique allowing the direct experimental measurement of Na+ currents in the AIS. We determined the AIS Na+ current, from fluorescence measurements at temporal resolution of 100 µs and pixel resolution of half a micron, in pyramidal neurons of the layer-5 of the somatosensory cortex from brain slices of the mouse. We identified a subthreshold current before the AP, a fast inactivating current peaking during the rise of the AP and a persistent current during the AP repolarisation. We correlated the kinetics of the current at different distances from the soma with the kinetics of the somatic AP. We quantitatively compared the experimentally measured Na+ current with the current obtained by computer simulation of published NEURON models and we show how the present approach can lead to the correct estimate of the native behaviour of Na+ channels. Thus, it is expected that the present method will be adopted to investigate the function of different channel types under physiological or pathological conditions.

Control of Neuronal Output by Inhibition at the Axon Initial Segment

1990 ◽  
Vol 2 (3) ◽  
pp. 283-292 ◽  
Author(s):  
Rodney J. Douglas ◽  
Kevan A. C. Martin
Keyword(s):  
Visual Cortex ◽  
Action Potential ◽  
Initial Segment ◽  
Compartmental Model ◽  
Pyramidal Neurons ◽  
Axon Initial Segment ◽  
Synaptic Current ◽  
Basket Cells ◽  
Excitatory Synaptic Current ◽  
Neuronal Output

We examine the effect of inhibition on the axon initial segment (AIS) by the chandelier (“axoaxonic”) cells, using a simplified compartmental model of actual pyramidal neurons from cat visual cortex. We show that within generally accepted ranges, inhibition at the AIS cannot completely prevent action potential discharge: only small amounts of excitatory synaptic current can be inhibited. Moderate amounts of excitatory current always result in action potential discharge, despite AIS inhibition. Inhibition of the somadendrite by basket cells enhances the effect of AIS inhibition and vice versa. Thus the axoaxonic cells may act synergistically with basket cells: the AIS inhibition increases the threshold for action potential discharge, the basket cells then control the suprathreshold discharge.

scholarly journals Functional microstructure of CaV-mediated calcium signaling in the axon initial segment

2020 ◽  
Author(s):  
Anna M Lipkin ◽  
Margaret M Cunniff ◽  
Perry WE Spratt ◽  
Stefan M Lemke ◽  
Kevin J Bender
Keyword(s):  
Calcium Channels ◽  
Action Potential ◽  
High Speed ◽  
Initial Segment ◽  
Laser Scanning ◽  
Pyramidal Neurons ◽  
Calcium Influx ◽  
Axon Initial Segment ◽  
Spatiotemporal Resolution ◽  
Sodium Potassium

ABSTRACTThe axon initial segment (AIS) is a specialized neuronal compartment in which synaptic input is converted into action potential output. This process is supported by a diverse complement of sodium, potassium, and calcium channels (CaV). Different classes of sodium and potassium channels are scaffolded at specific sites within the AIS, conferring unique functions, but how calcium channels are functionally distributed within the AIS is unclear. Here, we utilize conventional 2-photon laser scanning and diffraction-limited, high-speed spot 2-photon imaging to resolve action potential-evoked calcium dynamics in the AIS with high spatiotemporal resolution. In mouse layer 5 prefrontal pyramidal neurons, calcium influx was mediated by a mix of CaV2 and CaV3 channels that differentially localized to discrete regions. CaV3 functionally localized to produce nanodomain hotspots of calcium influx that coupled to ryanodine-dependent stores, whereas CaV2 localized to non-hotspot regions. Thus, different pools of CaVs appear to play distinct roles in AIS function.

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.

scholarly journals Nanoscale architecture of the axon initial segment reveals an organized and robust scaffold

2015 ◽  
Author(s):  
Christophe Leterrier ◽  
Jean Potier ◽  
Ghislaine Caillol ◽  
Claire Debarnot ◽  
Fanny Rueda Boroni ◽  
...  
Keyword(s):  
Action Potentials ◽  
Initial Segment ◽  
Axon Initial Segment ◽  
Molecular Architecture ◽  
Physiological Functions ◽  
Structural Stabilization ◽  
Ankyrin G ◽  
Stochastic Optical Reconstruction Microscopy ◽  
Optical Reconstruction ◽  
Actin Rings

The Axon Initial Segment [AIS], located within the first 30 μm of the axon, has two essential roles in generating action potentials and maintaining axonal identity. AIS assembly depends on a βIV-spectrin / ankyrin G scaffold, but its macromolecular arrangement is not well understood. Here we quantitatively determined the AIS nanoscale architecture using STochastic Optical Reconstruction Microscopy [STORM]. First we directly demonstrate that the 190-nm periodicity of the AIS submembrane lattice results from longitudinal, head-to-head βIV-spectrin molecules connecting actin rings. Using multicolor 3D-STORM, we resolve the nanoscale organization of ankyrin G: its aminoterminus associates with the submembrane lattice, whereas the carboxyterminus radially extends (~32 nm on average) toward the cytosol. This AIS nano-architecture is highly resistant to cytoskeletal perturbations, advocating its role in structural stabilization. Our findings provide a comprehensive view of the AIS molecular architecture, and will help understanding the crucial physiological functions of this compartment.

scholarly journals Covariation of axon initial segment location and dendritic tree normalizes the somatic action potential

2016 ◽  
Vol 113 (51) ◽  
pp. 14841-14846 ◽  
Author(s):  
Mustafa S. Hamada ◽  
Sarah Goethals ◽  
Sharon I. de Vries ◽  
Romain Brette ◽  
Maarten H. P. Kole
Keyword(s):  
Action Potential ◽  
Initial Segment ◽  
Pyramidal Neurons ◽  
Dendritic Tree ◽  
Apical Dendrite ◽  
Axial Current ◽  
Axon Initial Segment ◽  
Output Code ◽  
The Face ◽  
Dendritic Complexity

In mammalian neurons, the axon initial segment (AIS) electrically connects the somatodendritic compartment with the axon and converts the incoming synaptic voltage changes into a temporally precise action potential (AP) output code. Although axons often emanate directly from the soma, they may also originate more distally from a dendrite, the implications of which are not well-understood. Here, we show that one-third of the thick-tufted layer 5 pyramidal neurons have an axon originating from a dendrite and are characterized by a reduced dendritic complexity and thinner main apical dendrite. Unexpectedly, the rising phase of somatic APs is electrically indistinguishable between neurons with a somatic or a dendritic axon origin. Cable analysis of the neurons indicated that the axonal axial current is inversely proportional to the AIS distance, denoting the path length between the soma and the start of the AIS, and to produce invariant somatic APs, it must scale with the local somatodendritic capacitance. In agreement, AIS distance inversely correlates with the apical dendrite diameter, and model simulations confirmed that the covariation suffices to normalize the somatic AP waveform. Therefore, in pyramidal neurons, the AIS location is finely tuned with the somatodendritic capacitive load, serving as a homeostatic regulation of the somatic AP in the face of diverse neuronal morphologies.

scholarly journals NuMA1 promotes axon initial segment assembly through inhibition of endocytosis

2019 ◽  
pp. jcb.201907048 ◽  
Author(s):  
Tomohiro Torii ◽  
Yuki Ogawa ◽  
Cheng-Hsin Liu ◽  
Tammy Szu-Yu Ho ◽  
Hamdan Hamdan ◽  
...  
Keyword(s):  
Transient Expression ◽  
Action Potentials ◽  
Initial Segment ◽  
Axon Initial Segment ◽  
Neonatal Mouse ◽  
Scaffolding Protein ◽  
Differential Proteomics ◽  
Mitotic Apparatus ◽  
Axon Initial Segments ◽  
Protein 4.1B

Axon initial segments (AISs) initiate action potentials and regulate the trafficking of vesicles between somatodendritic and axonal compartments. However, the mechanisms controlling AIS assembly remain poorly defined. We performed differential proteomics and found nuclear mitotic apparatus protein 1 (NuMA1) is downregulated in AIS-deficient neonatal mouse brains and neurons. NuMA1 is transiently located at the AIS during development where it interacts with the scaffolding protein 4.1B and the dynein regulator lissencephaly 1 (Lis1). Silencing NuMA1 or protein 4.1B by shRNA disrupts AIS assembly, but not maintenance. Silencing Lis1 or overexpressing NuMA1 during AIS assembly increased the density of AIS proteins, including ankyrinG and neurofascin-186 (NF186). NuMA1 inhibits the endocytosis of AIS NF186 by impeding Lis1’s interaction with doublecortin, a potent facilitator of NF186 endocytosis. Our results indicate the transient expression and AIS localization of NuMA1 stabilizes the developing AIS by inhibiting endocytosis and removal of AIS proteins.

Selective presence of a giant saccular organelle in the axon initial segment of a subpopulation of layer V pyramidal neurons

2013 ◽  
Vol 220 (2) ◽  
pp. 869-884 ◽  
Author(s):  
Alejandro Antón-Fernández ◽  
Pablo Rubio-Garrido ◽  
Javier DeFelipe ◽  
Alberto Muñoz
Keyword(s):  
Initial Segment ◽  
Pyramidal Neurons ◽  
Axon Initial Segment ◽  
Layer V

scholarly journals Theoretical relation between axon initial segment geometry and excitability

2019 ◽  
Author(s):  
Sarah Goethals ◽  
Romain Brette
Keyword(s):  
Theoretical Analysis ◽  
Action Potentials ◽  
Simple Formula ◽  
Initial Segment ◽  
Axon Initial Segment ◽  
Confounding Factors ◽  
Theoretical Relation ◽  
Modest Increase ◽  
The Many ◽  
The Impact

AbstractIn most vertebrate neurons, action potentials are triggered at the distal end of the axon initial segment (AIS). Both position and length of the AIS vary across and within neuron types, with activity, development and pathology. What is the impact of AIS geometry on excitability? Direct empirical assessment has proven difficult because of the many potential confounding factors. Here we carried a principled theoretical analysis to answer this question. We provide a simple formula relating AIS geometry and sodium conductance density to the somatic voltage threshold. A distal shift of the AIS normally produces a (modest) increase in excitability, but we explain how this pattern can reverse if a hyperpolarizing current is present at the AIS, due to resistive coupling with the soma. This work provides a theoretical tool to assess the significance of structural AIS plasticity for electrical function.

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