action potential initiation
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2021 ◽  
Author(s):  
Petra Wahle ◽  
Eric Sobierajski ◽  
Ina Gasterstädt ◽  
Nadja Lehmann ◽  
Susanna Weber ◽  
...  

The canonical view of neuronal function is that inputs are received by dendrites and somata, become integrated in the somatodendritic compartment and upon reaching a sufficient threshold, generate axonal output with axons emerging from the cell body. The latter is not necessarily the case. Instead, axons may originate from dendrites. The terms “axon carrying dendrite” (AcD) and “AcD neurons” have been coined to describe this feature. Here, we report on the diversity of axon origins in neocortical pyramidal cells. We found that in non-primates (rodent, cat, ferret, pig), 10-21% of pyramidal cells of layers II-VI had an AcD. In marked contrast, in macaque and human, this proportion was lower, and it was particularly low for supragranular neurons. Unexpectedly, pyramidal cells in the white matter of postnatal cat and aged human cortex exhibit AcDs to much higher percentages. In rodent hippocampus, AcD cells are functionally ’privileged‘, since inputs here can circumvent somatic integration and lead to immediate action potential initiation in the axon. Our findings expand the current knowledge regarding the distribution and proportion of AcD cells in neocortial regions of non-primate taxa, which strikingly differs from primates where these cells are mainly found in deeper layers and white matter.



2020 ◽  
Vol 319 (4) ◽  
pp. G443-G453
Author(s):  
Fei Ru ◽  
Nikoleta Pavelkova ◽  
Jeffrey L. Krajewski ◽  
Jeff S. McDermott ◽  
Bradley J. Undem ◽  
...  

We report that pharmacologically distinguishable voltage-gated sodium channels (NaV1) mediate action potential initiation at low (innocuous) versus high (noxious) intensity of esophageal distention in nerve terminals of vagal nodose C-fibers. Action potential initiation at low intensity is entirely dependent on NaV1.7; however, additional tetrodotoxin (TTX)-sensitive NaV1s are recruited at higher intensity of distention. This is the first demonstration that NaV1s underlying action potential initiation in visceral C-fibers depend on the intensity of the stimulus.



eLife ◽  
2020 ◽  
Vol 9 ◽  
Author(s):  
Aniket Ghosh ◽  
Elise LV Malavasi ◽  
Diane L Sherman ◽  
Peter J Brophy

Ion channel complexes promote action potential initiation at the mammalian axon initial segment (AIS), and modulation of AIS size by recruitment or loss of proteins can influence neuron excitability. Although endocytosis contributes to AIS turnover, how membrane proteins traffic to this proximal axonal domain is incompletely understood. Neurofascin186 (Nfasc186) has an essential role in stabilising the AIS complex to the proximal axon, and the AIS channel protein Kv7.3 regulates neuron excitability. Therefore, we have studied how these proteins reach the AIS. Vesicles transport Nfasc186 to the soma and axon terminal where they fuse with the neuronal plasma membrane. Nfasc186 is highly mobile after insertion in the axonal membrane and diffuses bidirectionally until immobilised at the AIS through its interaction with AnkyrinG. Kv7.3 is similarly recruited to the AIS. This study reveals how key proteins are delivered to the AIS and thereby how they may contribute to its functional plasticity.



eLife ◽  
2019 ◽  
Vol 8 ◽  
Author(s):  
Jonathan H Cornford ◽  
Marion S Mercier ◽  
Marco Leite ◽  
Vincent Magloire ◽  
Michael Häusser ◽  
...  

Parvalbumin-expressing (PV+) GABAergic interneurons mediate feedforward and feedback inhibition and have a key role in gamma oscillations and information processing. The importance of fast synaptic recruitment and action potential initiation and repolarization, and rapid synchronous GABA release by PV+ cells, is well established. In contrast, the functional significance of PV+ cell NMDA receptors (NMDARs), which generate relatively slow postsynaptic currents, is unclear. Underlining their potential importance, several studies implicate PV+ cell NMDAR disruption in impaired network function and circuit pathologies. Here, we show that dendritic NMDARs underlie supralinear integration of feedback excitation from local pyramidal neurons onto mouse CA1 PV+ cells. Furthermore, by incorporating NMDARs at feedback connections onto PV+ cells in spiking networks, we show that these receptors enable cooperative recruitment of PV+ interneurons, strengthening and stabilising principal cell assemblies. Failure of this phenomenon provides a parsimonious explanation for cognitive and sensory gating deficits in pathologies with impaired PV+ NMDAR signalling.



2019 ◽  
Author(s):  
Amr Abouelezz ◽  
Holly Stefen ◽  
Mikael Segerstråle ◽  
David Micinski ◽  
Rimante Minkeviciene ◽  
...  

ABSTRACTThe axon initial segment (AIS) is the site of action potential initiation and serves as a vesicular filter and diffusion barrier that help maintain neuronal polarity. Recent studies have revealed details about a specialized structural complex in the AIS. While an intact actin cytoskeleton is required for AIS formation, pharmacological disruption of actin polymerization compromises the AIS vesicle filter but does not affect overall AIS structure. In this study, we found that the tropomyosin isoform Tpm3.1 decorates a population of relatively stable actin filaments in the AIS. Inhibiting Tpm3.1 in cultured hippocampal neurons led to the loss of AIS structure, the AIS vesicle filter, the clustering of sodium ion channels, and reduced firing frequency. We propose that Tpm3.1-decorated actin filaments form a stable actin filament network under the AIS membrane which provides a scaffold for membrane organization and AIS proteins.



Author(s):  
Yeonjoo Yoo ◽  
Fabrizio Gabbiani

Computational modeling is essential to understand how the complex dendritic structure and membrane properties of a neuron process input signals to generate output signals. Compartmental models describe how inputs, such as synaptic currents, affect a neuron’s membrane potential and produce outputs, such as action potentials, by converting membrane properties into the components of an electrical circuit. The simplest such model consists of a single compartment with a leakage conductance which represents a neuron having spatially uniform membrane potential and a constant conductance summarizing the combined effect of every ion flowing across the neuron’s membrane. The Hodgkin-Huxley model introduces two additional active channels; the sodium channel and the delayed rectifier potassium channel whose associated conductances change depending on the membrane potential and that are described by an additional set of three nonlinear differential equations. Since its conception in 1952, many kinds of active channels have been discovered with a variety of characteristics that can successfully be modeled within the same framework. As the membrane potential varies spatially in a neuron, the next refinement consists in describing a neuron as an electric cable to account for membrane potential attenuation and signal propagation along dendritic or axonal processes. A discrete version of the cable equation results in compartments with possibly different properties, such as different types of ion channels or spatially varying maximum conductances to model changes in channel densities. Branching neural processes such as dendrites can be modeled with the cable equation by considering the junctions of cables with different radii and electrical properties. Single neuron computational models are used to investigate a variety of topics and reveal insights that cannot be evidenced directly by experimental observation. Studies on action potential initiation and on synaptic integration provide prototypical examples illustrating why computational models are essential. Modeling action potential initiation constrains the localization and density of channels required to reproduce experimental observations, while modeling synaptic integration sheds light on the interaction between the morphological and physiological characteristics of dendrites. Finally, reduced compartmental models demonstrate how a simplified morphological structure supplemented by a small number of ion channel-related variables can provide clear explanations about complex intracellular membrane potential dynamics.



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