scholarly journals Etomidate Reduces Initiation of Backpropagating Dendritic Action Potentials: Implications for Sensory Processing and Synaptic Plasticity During Anesthesia

2007 ◽  
Vol 97 (3) ◽  
pp. 2373-2384 ◽  
Author(s):  
Erwin H. van den Burg ◽  
Jacob Engelmann ◽  
João Bacelo ◽  
Leonel Gómez ◽  
Kirsty Grant
Keyword(s):  
Action Potential ◽  
Sensory Processing ◽  
Action Potentials ◽  
Molecular Layer ◽  
Current Source ◽  
Spike Timing ◽  
Stimulus Strength ◽  
Action Potential Initiation ◽  
Potential Initiation

Anesthetics may induce specific changes that alter the balance of activity within neural networks. Here we describe the effects of the GABAA receptor potentiating anesthetic etomidate on sensory processing, studied in a cerebellum-like structure, the electrosensory lateral line lobe (ELL) of mormyrid fish, in vitro. Previous studies have shown that the ELL integrates sensory input and removes predictable features by comparing reafferent sensory signals with a descending electromotor command-driven corollary signal that arrives in part through parallel fiber synapses with the apical dendrites of GABAergic interneurons. These synapses show spike timing–dependent depression when presynaptic activation is associated with postsynaptic backpropagating dendritic action potentials. Under etomidate, almost all neurons become tonically hyperpolarized. The threshold for action potential initiation increased for both synaptic activation and direct intracellular depolarization. Synaptically evoked inhibitory postsynaptic potentials (IPSPs) were also strongly potentiated and prolonged. Current source density analysis showed that backpropagation of action potentials through the apical dendritic arborization in the molecular layer was reduced but could be restored by increasing stimulus strength. These effects of etomidate were blocked by bicuculline or picrotoxin. It is concluded that etomidate affects both tonic and phasic inhibitory conductances at GABAA receptors and that increased shunting inhibition at the level of the proximal dendrites also contributes to increasing the threshold for action potential backpropagation. When stimulus strength is sufficient to evoke backpropagation, repetitive association of synaptic excitation with postsynaptic action potential initiation still results in synaptic depression, showing that etomidate does not interfere with the molecular mechanism underlying plastic modulation.

Properties of Action-Potential Initiation in Neocortical Pyramidal Cells: Evidence From Whole Cell Axon Recordings

2007 ◽  
Vol 97 (1) ◽  
pp. 746-760 ◽  
Author(s):  
Yousheng Shu ◽  
Alvaro Duque ◽  
Yuguo Yu ◽  
Bilal Haider ◽  
David A. McCormick
Keyword(s):  
Action Potential ◽  
Action Potentials ◽  
Initial Segment ◽  
Pyramidal Cells ◽  
Synaptic Activity ◽  
Up States ◽  
Action Potential Initiation ◽  
Potential Initiation

Cortical pyramidal cells are constantly bombarded by synaptic activity, much of which arises from other cortical neurons, both in normal conditions and during epileptic seizures. The action potentials generated by barrages of synaptic activity may exhibit a variable site of origin. Here we performed simultaneous whole cell recordings from the soma and axon or soma and apical dendrite of layer 5 pyramidal neurons during normal recurrent network activity (up states), the intrasomatic or intradendritic injection of artificial synaptic barrages, and during epileptiform discharges in vitro. We demonstrate that under all of these conditions, the real or artificial synaptic bombardments propagate through the dendrosomatic-axonal arbor and consistently initiate action potentials in the axon initial segment that then propagate to other parts of the cell. Action potentials recorded intracellularly in vivo during up states and in response to visual stimulation exhibit properties indicating that they are typically initiated in the axon. Intracortical axons were particularly well suited to faithfully follow the generation of action potentials by the axon initial segment. Action-potential generation was more reliable in the distal axon than at the soma during epileptiform activity. These results indicate that the axon is the preferred site of action-potential initiation in cortical pyramidal cells, both in vivo and in vitro, with state-dependent back propagation through the somatic and dendritic compartments.

Transduction mechanisms in airway sensory nerves

2006 ◽  
Vol 101 (3) ◽  
pp. 950-959 ◽  
Author(s):  
Thomas Taylor-Clark ◽  
Bradley J. Undem
Keyword(s):  
Action Potential ◽  
Action Potentials ◽  
Membrane Depolarization ◽  
Sensory Nerves ◽  
Metabotropic Receptors ◽  
Metabotropic Receptor ◽  
Transduction Mechanisms ◽  
The Central Nervous System ◽  
Action Potential Initiation ◽  
Potential Initiation

The induction of action potentials in airway sensory nerves relies on events leading to the opening of cation channels in the nerve terminal membrane and subsequent membrane depolarization. If the membrane depolarization is of sufficient rate and amplitude, action potential initiation will occur. The action potentials are then conducted to the central nervous system, leading to the initiation of various sensations and cardiorespiratory reflexes. Triggering events in airway sensory nerves include mechanical perturbation, inflammatory mediators, pH, temperature, and osmolarity acting through a variety of ionotropic and metabotropic receptors. Action potential initiation can be modulated (positively or negatively) through independent mechanisms caused mainly by autacoids and other metabotropic receptor ligands. Finally, gene expression of sensory nerves can be altered in adult mammals. This neuroplasticity can change the function of sensory nerves and likely involve both neurotrophin and use-dependent mechanisms. Here we provide a brief overview of some of the transduction mechanisms underlying these events.

scholarly journals Polarized localization of voltage-gated Na+ channels is regulated by concerted FGF13 and FGF14 action

2016 ◽  
Vol 113 (19) ◽  
pp. E2665-E2674 ◽  
Author(s):  
Juan Lorenzo Pablo ◽  
Chaojian Wang ◽  
Matthew M. Presby ◽  
Geoffrey S. Pitt
Keyword(s):  
Action Potential ◽  
Hippocampal Neurons ◽  
Single Point ◽  
Point Mutations ◽  
Surface Expression ◽  
Voltage Gated ◽  
Voltage Gated Sodium Channels ◽  
Action Potential Initiation ◽  
Potential Initiation

Clustering of voltage-gated sodium channels (VGSCs) within the neuronal axon initial segment (AIS) is critical for efficient action potential initiation. Although initially inserted into both somatodendritic and axonal membranes, VGSCs are concentrated within the axon through mechanisms that include preferential axonal targeting and selective somatodendritic endocytosis. How the endocytic machinery specifically targets somatic VGSCs is unknown. Here, using knockdown strategies, we show that noncanonical FGF13 binds directly to VGSCs in hippocampal neurons to limit their somatodendritic surface expression, although exerting little effect on VGSCs within the AIS. In contrast, homologous FGF14, which is highly concentrated in the proximal axon, binds directly to VGSCs to promote their axonal localization. Single-point mutations in FGF13 or FGF14 abrogating VGSC interaction in vitro cannot support these specific functions in neurons. Thus, our data show how the concerted actions of FGF13 and FGF14 regulate the polarized localization of VGSCs that supports efficient action potential initiation.

scholarly journals Modeling Action Potential Initiation and Back-Propagation in Dendrites of Cultured Rat Motoneurons

1998 ◽  
Vol 80 (2) ◽  
pp. 715-729 ◽  
Author(s):  
Hans-R. Lüscher ◽  
Matthew E. Larkum
Keyword(s):  
Action Potential ◽  
Action Potentials ◽  
Initial Segment ◽  
Back Propagation ◽  
Channel Density ◽  
Axon Hillock ◽  
Dendritic Membrane ◽  
Action Potential Initiation ◽  
Spike Initiation ◽  
Potential Initiation

Lüscher, Hans-R. and Matthew E. Larkum. Modeling action potential initiation and back-propagation in dendrites of cultured rat motoneurons. J. Neurophysiol. 80: 715–729, 1998. Regardless of the site of current injection, action potentials usually originate at or near the soma and propagate decrementally back into the dendrites. This phenomenon has been observed in neocortical pyramidal cells as well as in cultured motoneurons. Here we show that action potentials in motoneurons can be initiated in the dendrite as well, resulting in a biphasic dendritic action potential. We present a model of spinal motoneurons that is consistent with observed physiological properties of spike initiation in the initial segment/axon hillock region and action potential back-propagation into the dendritic tree. It accurately reproduces the results presented by Larkum et al. on motoneurons in organotypic rat spinal cord slice cultures. A high Na+-channel density of ḡ Na = 700 mS/cm2 at the axon hillock/initial segment region was required to secure antidromic invasion of the somato-dendritic membrane, whereas for the orthodromic direction, a Na+-channel density of ḡ Na = 1,200 mS/cm2 was required. A “weakly” excitable ( ḡ Na = 3 mS/cm2) dendritic membrane most accurately describes the experimentally observed attenuation of the back-propagated action potential. Careful analysis of the threshold conditions for action potential initiation at the initial segment or the dendrites revealed that, despite the lower voltage threshold for spike initiation in the initial segment, an action potential can be initiated in the dendrite before the initial segment fires a spike. Spike initiation in the dendrite depends on the passive cable properties of the dendritic membrane, its Na+-channel density, and local structural properties, mainly the diameter of the dendrites. Action potentials are initiated more easily in distal than in proximal dendrites. Whether or not such a dendritic action potential invades the soma with a subsequent initiation of a second action potential in the initial segment depends on the actual current source-load relation between the action potential approaching the soma and the electrical load of the soma together with the attached dendrites.

scholarly journals High Threshold, Proximal Initiation, and Slow Conduction Velocity of Action Potentials in Dentate Granule Neuron Mossy Fibers

2008 ◽  
Vol 100 (1) ◽  
pp. 281-291 ◽  
Author(s):  
Geraldine J. Kress ◽  
Margaret J. Dowling ◽  
Julian P. Meeks ◽  
Steven Mennerick
Keyword(s):  
Action Potential ◽  
Conduction Velocity ◽  
Action Potentials ◽  
Mossy Fiber ◽  
Hippocampal Slices ◽  
Mossy Fibers ◽  
Comparative Approach ◽  
Granule Neurons ◽  
Action Potential Initiation ◽  
Potential Initiation

Dentate granule neurons give rise to some of the smallest unmyelinated fibers in the mammalian CNS, the hippocampal mossy fibers. These neurons are also key regulators of physiological and pathophysiological information flow through the hippocampus. We took a comparative approach to studying mossy fiber action potential initiation and propagation in hippocampal slices from juvenile rats. Dentate granule neurons exhibited axonal action potential initiation significantly more proximal than CA3 pyramidal neurons. This conclusion was suggested by phase plot analysis of somatic action potentials and by local tetrodotoxin application to the axon and somatodendritic compartments. This conclusion was also verified by immunostaining for voltage-gated sodium channel alpha subunits and by direct dual soma/axonal recordings. Dentate neurons exhibited a significantly higher action potential threshold and slower axonal conduction velocity than CA3 neurons. We conclude that while the electrotonically proximal axon location of action potential initiation allows granule neurons to sensitively detect and integrate synaptic inputs, the neurons are sluggish to initiate and propagate an action potential.

Contribution of Nav1.8 Sodium Channels to Action Potential Electrogenesis in DRG Neurons

2001 ◽  
Vol 86 (2) ◽  
pp. 629-640 ◽  
Author(s):  
Muthukrishnan Renganathan ◽  
Theodore R. Cummins ◽  
Stephen G. Waxman
Keyword(s):  
Action Potential ◽  
Sodium Channels ◽  
Action Potentials ◽  
Input Resistance ◽  
Resting Membrane Potential ◽  
Drg Neurons ◽  
Significant Difference ◽  
Steady State Inactivation ◽  
Current Threshold

C-type dorsal root ganglion (DRG) neurons can generate tetrodotoxin-resistant (TTX-R) sodium-dependent action potentials. However, multiple sodium channels are expressed in these neurons, and the molecular identity of the TTX-R sodium channels that contribute to action potential production in these neurons has not been established. In this study, we used current-clamp recordings to compare action potential electrogenesis in Nav1.8 (+/+) and (−/−) small DRG neurons maintained for 2–8 h in vitro to examine the role of sodium channel Nav1.8 (α-SNS) in action potential electrogenesis. Although there was no significant difference in resting membrane potential, input resistance, current threshold, or voltage threshold in Nav1.8 (+/+) and (−/−) DRG neurons, there were significant differences in action potential electrogenesis. Most Nav1.8 (+/+) neurons generate all-or-none action potentials, whereas most of Nav1.8 (−/−) neurons produce smaller graded responses. The peak of the response was significantly reduced in Nav1.8 (−/−) neurons [31.5 ± 2.2 (SE) mV] compared with Nav1.8 (+/+) neurons (55.0 ± 4.3 mV). The maximum rise slope was 84.7 ± 11.2 mV/ms in Nav1.8 (+/+) neurons, significantly faster than in Nav1.8 (−/−) neurons where it was 47.2 ± 1.3 mV/ms. Calculations based on the action potential overshoot in Nav1.8 (+/+) and (−/−) neurons, following blockade of Ca2+ currents, indicate that Nav1.8 contributes a substantial fraction (80–90%) of the inward membrane current that flows during the rising phase of the action potential. We found that fast TTX-sensitive Na+ channels can produce all-or-none action potentials in some Nav1.8 (−/−) neurons but, presumably as a result of steady-state inactivation of these channels, electrogenesis in Nav1.8 (−/−) neurons is more sensitive to membrane depolarization than in Nav1.8 (+/+) neurons, and, in the absence of Nav1.8, is attenuated with even modest depolarization. These observations indicate that Nav1.8 contributes substantially to action potential electrogenesis in C-type DRG neurons.

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