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.

scholarly journals Differential Effects of Axon Initial Segment and Somatodendritic GABAA Receptors on Excitability Measures in Rat Dentate Granule Neurons

2011 ◽  
Vol 105 (1) ◽  
pp. 366-379 ◽  
Author(s):  
Patricio Rojas ◽  
Alejandro Akrouh ◽  
Lawrence N. Eisenman ◽  
Steven Mennerick
Keyword(s):  
Action Potential ◽  
Initial Segment ◽  
Input Resistance ◽  
Receptor Activation ◽  
Axon Initial Segment ◽  
Granule Neurons ◽  
Voltage Threshold ◽  
Granule Neuron ◽  
Action Potential Initiation ◽  
Potential Initiation

GABAA receptors are found on the somatodendritic compartment and on the axon initial segment of many principal neurons. The function of axonal receptors remains obscure, although it is widely assumed that axonal receptors must have a strong effect on excitability. We found that activation of GABAA receptors on the dentate granule neuron axon initial segment altered excitability by depolarizing the voltage threshold for action potential initiation under conditions that minimally affected overall cell input resistance. In contrast, activation of somatic GABAA receptors strongly depressed the input resistance of granule neurons without affecting the voltage threshold of action potential initiation. Although these effects were observed over a range of intracellular chloride concentrations, average voltage threshold was unaffected when ECl rendered GABAA axon initial segment responses explicitly excitatory. A compartment model of a granule neuron confirmed these experimental observations. Low ambient agonist concentrations designed to activate granule neuron tonic currents did not stimulate axonal receptors sufficiently to raise voltage threshold. Using excitatory postsynaptic current (EPSC)-like depolarizations, we show physiological consequences of axonal versus somatic GABAA receptor activation. With axonal inhibition, individual excitatory postsynaptic potentials (EPSPs) largely retained their amplitude and time course, but EPSPs that were suprathreshold under basal conditions failed to reach threshold with GABAA activation. By contrast, somatic inhibition depressed individual EPSPs because of strong shunting. Our results suggest that axonal GABAA receptors have a privileged effect on voltage threshold and that two major measures of neuronal excitability, voltage threshold and rheobase, are differentially affected by axonal and somatic GABAA receptor activation.

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.

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.

scholarly journals HCN channel-mediated neuromodulation can control action potential velocity and fidelity in central axons

eLife ◽  
2019 ◽  
Vol 8 ◽  
Author(s):  
Niklas Byczkowicz ◽  
Abdelmoneim Eshra ◽  
Jacqueline Montanaro ◽  
Andrea Trevisiol ◽  
Johannes Hirrlinger ◽  
...  
Keyword(s):  
Action Potential ◽  
Conduction Velocity ◽  
Mossy Fiber ◽  
Mossy Fibers ◽  
Cyclic Adenosine Monophosphate ◽  
Adenosine Monophosphate ◽  
Resting Membrane Potential ◽  
Immunogold Electron Microscopy ◽  
Hcn Channels ◽  
Hcn Channel

Hyperpolarization-activated cyclic-nucleotide-gated (HCN) channels control electrical rhythmicity and excitability in the heart and brain, but the function of HCN channels at the subcellular level in axons remains poorly understood. Here, we show that the action potential conduction velocity in both myelinated and unmyelinated central axons can be bidirectionally modulated by a HCN channel blocker, cyclic adenosine monophosphate (cAMP), and neuromodulators. Recordings from mouse cerebellar mossy fiber boutons show that HCN channels ensure reliable high-frequency firing and are strongly modulated by cAMP (EC50 40 µM; estimated endogenous cAMP concentration 13 µM). In addition, immunogold-electron microscopy revealed HCN2 as the dominating subunit in cerebellar mossy fibers. Computational modeling indicated that HCN2 channels control conduction velocity primarily by altering the resting membrane potential and are associated with significant metabolic costs. These results suggest that the cAMP-HCN pathway provides neuromodulators with an opportunity to finely tune energy consumption and temporal delays across axons in the brain.

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.

scholarly journals HCN channel-mediated neuromodulation can control action potential velocity and fidelity in central axons

2019 ◽  
Author(s):  
Niklas Byczkowicz ◽  
Abdelmoneim Eshra ◽  
Jacqueline Montanaro ◽  
Andrea Trevisiol ◽  
Johannes Hirrlinger ◽  
...  
Keyword(s):  
Action Potential ◽  
Conduction Velocity ◽  
Mossy Fiber ◽  
Mossy Fibers ◽  
Adenosine Monophosphate ◽  
Resting Membrane Potential ◽  
Immunogold Electron Microscopy ◽  
Hcn Channels ◽  
Channel Blockers ◽  
Hcn Channel

AbstractHyperpolarization-activated cyclic-nucleotide-gated (HCN) channels control electrical rhythmicity and excitability in the heart and brain, but the function of HCN channels at subcellular level in axons remains poorly understood. Here, we show that the action potential conduction velocity in both myelinated and unmyelinated central axons can bidirectionally be modulated by HCN channel blockers, cyclic adenosine monophosphate (cAMP), and neuromodulators. Recordings from mice cerebellar mossy fiber boutons show that HCN channels ensure reliable high-frequency firing and are strongly modulated by cAMP (EC50 40 µM; estimated endogenous cAMP concentration 13 µM). In accord, immunogold-electron microscopy revealed HCN2 as the dominating subunit in cerebellar mossy fibers. Computational modeling indicated that HCN2 channels control conduction velocity primarily via altering the resting membrane potential and was associated with significant metabolic costs. These results suggest that the cAMP-HCN pathway provides neuromodulators an opportunity to finely tune energy consumption and temporal delays across axons in the brain.

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 Zinc Enhances the Inhibitory Effects of Strychnine-Sensitive Glycine Receptors in Mouse Hippocampal Neurons

2007 ◽  
Vol 98 (6) ◽  
pp. 3666-3676 ◽  
Author(s):  
Hai Xia Zhang ◽  
Liu Lin Thio
Keyword(s):  
Action Potential ◽  
Action Potentials ◽  
Hippocampal Neurons ◽  
Neuronal Excitability ◽  
Hippocampal Slices ◽  
Glycine Receptors ◽  
Inhibitory Effects ◽  
Action Potential Firing ◽  
Embryonic Mouse ◽  
Potential Firing

Although extracellular Zn2+ is an endogenous biphasic modulator of strychnine-sensitive glycine receptors (GlyRs), the physiological significance of this modulation remains poorly understood. Zn2+ modulation of GlyR may be especially important in the hippocampus where presynaptic Zn2+ is abundant. Using cultured embryonic mouse hippocampal neurons, we examined whether 1 μM Zn2+, a potentiating concentration, enhances the inhibitory effects of GlyRs activated by sustained glycine applications. Sustained 20 μM glycine (EC25) applications alone did not decrease the number of action potentials evoked by depolarizing steps, but they did in 1 μM Zn2+. At least part of this effect resulted from Zn2+ enhancing the GlyR-induced decrease in input resistance. Sustained 20 μM glycine applications alone did not alter neuronal bursting, a form of hyperexcitability induced by omitting extracellular Mg2+. However, sustained 20 μM glycine applications depressed neuronal bursting in 1 μM Zn2+. Zn2+ did not enhance the inhibitory effects of sustained 60 μM glycine (EC70) applications in these paradigms. These results suggest that tonic GlyR activation could decrease neuronal excitability. To test this possibility, we examined the effect of the GlyR antagonist strychnine and the Zn2+ chelator tricine on action potential firing by CA1 pyramidal neurons in mouse hippocampal slices. Co-applying strychnine and tricine slightly but significantly increased the number of action potentials fired during a depolarizing current step and decreased the rheobase for action potential firing. Thus Zn2+ may modulate neuronal excitability normally and in pathological conditions such as seizures by potentiating GlyRs tonically activated by low agonist concentrations.

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