The Hodgkin-Huxley Model of Action Potential Generation

Author(s):  
Christof Koch

The vast majority of nerve cells generate a series of brief voltage pulses in response to vigorous input. These pulses, also referred to as action potentials or spikes, originate at or close to the cell body, and propagate down the axon at constant velocity and amplitude. Fig. 6.1 shows the shape of the action potential from a number of different neuronal and nonneuronal preparations. Action potentials come in a variety of shapes; common to all is the all-or-none depolarization of the membrane beyond 0. That is, if the voltage fails to exceed a particular threshold value, no spike is initiated and the potential returns to its baseline level. If the voltage threshold is exceeded, the membrane executes a stereotyped voltage trajectory that reflects membrane properties and not the input. As evident in Fig. 6.1, the shape of the action potential can vary enormously from cell type to cell type. When inserting an electrode into a brain, the small all-or-none electrical events one observes extracellularly are usually due to spikes that are initiated close to the cell body and that propagate along the axons. When measuring the electrical potential across the membrane, these spikes peak between +10 and +30 mV and are over (depending on the temperature) within 1 or 2 msec. Other all-or-none events, such as the complex spikes in cerebellar Purkinje cells or bursting pyramidal cells in cortex, show a more complex wave form with one or more fast spikes superimposed onto an underlying, much slower depolarization. Finally, under certain conditions, the dendritic membrane can also generate all-or-none events that are much slower than somatic spikes, usually on the order to 50-100 msec or longer. We will treat these events and their possible significance in Chap. 19. Only a small fraction of all neurons is unable—under physiological conditions—to generate action potentials, making exclusive use of graded signals. Examples of such nonspiking cells, usually spatially compact, can be found in the distal retina (e.g., bipolar, horizontal, and certain types of amacrine cells) and many neurons in the sensory-motor pathway of invertebrates (Roberts and Bush, 1981).

2005 ◽  
Vol 94 (5) ◽  
pp. 3357-3367 ◽  
Author(s):  
Elodie Christophe ◽  
Nathalie Doerflinger ◽  
Daniel J. Lavery ◽  
Zoltán Molnár ◽  
Serge Charpak ◽  
...  

Previous studies have shown that layer V pyramidal neurons projecting either to subcortical structures or the contralateral cortex undergo different morphological and electrophysiological patterns of development during the first three postnatal weeks. To isolate the determinants of this differential maturation, we analyzed the gene expression and intrinsic membrane properties of layer V pyramidal neurons projecting either to the superior colliculus (SC cells) or the contralateral cortex (CC cells) by combining whole cell recordings and single-cell RT-PCR in acute slices prepared from postnatal day (P) 5–7 or P21–30 old mice. Among the 24 genes tested, the calcium channel subunits α1B and α1C, the protease Nexin 1, and the calcium-binding protein calbindin were differentially expressed in adult SC and CC cells and the potassium channel subunit Kv4.3 was expressed preferentially in CC cells at both stages of development. Intrinsic membrane properties, including input resistance, amplitude of the hyperpolarization-activated current, and action potential threshold, differed quantitatively between the two populations as early as from the first postnatal week and persisted throughout adulthood. However, the two cell types had similar regular action potential firing behaviors at all developmental stages. Surprisingly, when we increased the duration of anesthesia with ketamine–xylazine or pentobarbital before decapitation, a proportion of mature SC cells, but not CC cells, fired bursts of action potentials. Together these results indicate that the two populations of layer V pyramidal neurons already start to differ during the first postnatal week and exhibit different firing capabilities after anesthesia.


2015 ◽  
Vol 39 (1) ◽  
pp. 15-26 ◽  
Author(s):  
Javier Rodriguez-Falces

A concept of major importance in human electrophysiology studies is the process by which activation of an excitable cell results in a rapid rise and fall of the electrical membrane potential, the so-called action potential. Hodgkin and Huxley proposed a model to explain the ionic mechanisms underlying the formation of action potentials. However, this model is unsuitably complex for teaching purposes. In addition, the Hodgkin and Huxley approach describes the shape of the action potential only in terms of ionic currents, i.e., it is unable to explain the electrical significance of the action potential or describe the electrical field arising from this source using basic concepts of electromagnetic theory. The goal of the present report was to propose a new model to describe the electrical behaviour of the action potential in terms of elementary electrical sources (in particular, dipoles). The efficacy of this model was tested through a closed-book written exam. The proposed model increased the ability of students to appreciate the distributed character of the action potential and also to recognize that this source spreads out along the fiber as function of space. In addition, the new approach allowed students to realize that the amplitude and sign of the extracellular electrical potential arising from the action potential are determined by the spatial derivative of this intracellular source. The proposed model, which incorporates intuitive graphical representations, has improved students' understanding of the electrical potentials generated by bioelectrical sources and has heightened their interest in bioelectricity.


2003 ◽  
Vol 89 (2) ◽  
pp. 657-664 ◽  
Author(s):  
Robert R. Buss ◽  
Charles W. Bourque ◽  
Pierre Drapeau

The physiological and pharmacological properties of the motoneuron membrane and action potential were investigated in larval zebrafish using whole cell patch current-clamp recording techniques. Action potentials were eliminated in tetrodotoxin, repolarized by tetraethylammonium (TEA) and 3,4-diaminopyridine (3,4-AP)-sensitive potassium conductances, and had a cobalt-sensitive, high-threshold calcium component. Depolarizing current injection evoked a brief (approximately 10–30 ms) burst of action potentials that was terminated by strong, outwardly rectifying voltage-activated potassium and calcium-dependent conductances. In the presence of intracellular cesium ions, a prolonged plateau potential often followed brief depolarizations. During larval development (hatching to free-swimming), the resting membrane conductance increased in a population of motoneurons, which tended to reduce the apparent outward rectification of the membrane. The conductances contributing to action potential burst termination are hypothesized to play a role in patterning the synaptically driven motoneuron output in these rapidly swimming fish.


2000 ◽  
Vol 84 (5) ◽  
pp. 2398-2408 ◽  
Author(s):  
Nathan P. Staff ◽  
Hae-Yoon Jung ◽  
Tara Thiagarajan ◽  
Michael Yao ◽  
Nelson Spruston

Action potentials are the end product of synaptic integration, a process influenced by resting and active neuronal membrane properties. Diversity in these properties contributes to specialized mechanisms of synaptic integration and action potential firing, which are likely to be of functional significance within neural circuits. In the hippocampus, the majority of subicular pyramidal neurons fire high-frequency bursts of action potentials, whereas CA1 pyramidal neurons exhibit regular spiking behavior when subjected to direct somatic current injection. Using patch-clamp recordings from morphologically identified neurons in hippocampal slices, we analyzed and compared the resting and active membrane properties of pyramidal neurons in the subiculum and CA1 regions of the hippocampus. In response to direct somatic current injection, three subicular firing types were identified (regular spiking, weak bursting, and strong bursting), while all CA1 neurons were regular spiking. Within subiculum strong bursting neurons were found preferentially further away from the CA1 subregion. Input resistance ( R N), membrane time constant (τm), and depolarizing “sag” in response to hyperpolarizing current pulses were similar in all subicular neurons, while R N and τm were significantly larger in CA1 neurons. The first spike of all subicular neurons exhibited similar action potential properties; CA1 action potentials exhibited faster rising rates, greater amplitudes, and wider half-widths than subicular action potentials. Therefore both the resting and active properties of CA1 pyramidal neurons are distinct from those of subicular neurons, which form a related class of neurons, differing in their propensity to burst. We also found that both regular spiking subicular and CA1 neurons could be transformed into a burst firing mode by application of a low concentration of 4-aminopyridine, suggesting that in both hippocampal subfields, firing properties are regulated by a slowly inactivating, D-type potassium current. The ability of all subicular pyramidal neurons to burst strengthens the notion that they form a single neuronal class, sharing a burst generating mechanism that is stronger in some cells than others.


Author(s):  
Leonard K. Kaczmarek

The intrinsic electrical properties of neurons are extremely varied. For example, the width of action potentials in different neurons varies by more than an order of magnitude. In response to prolonged stimulation, some neurons generate repeated action potential hundreds of times a second, while others fire only a single action potential or adapt very rapidly. These differences result from the expression of different types of ion channels in the plasma membrane. The dominant channels that shape neuronal firing patterns are those that are selective for sodium, calcium, and potassium ions. This chapter provides a brief overview of the biophysical properties of each of these classes of channel, their role in shaping the electrical personality of a neuron, and how interactions of these channels with cytoplasmic factors shape the overall cell biology of a neuron.


1984 ◽  
Vol 52 (1) ◽  
pp. 126-142 ◽  
Author(s):  
C. P. Taylor ◽  
F. E. Dudek

The effects of electrical fields from antidromic stimulation of CA1 pyramidal cells were studied in slices of rat hippocampus in which chemical synaptic transmission had been blocked by superfusion with physiological solution containing Mn2+ and lowered concentration of Ca2+. Differential voltage recordings were made between two microelectrode positions, on intracellular to a pyramidal cell and the other in the adjacent extracellular space. This technique revealed brief transmembrane depolarizations that occurred synchronously with negative-going extracellular population spikes in the adjacent cell body layer. Glial cells in this region did not exhibit these depolarizations. In some pyramidal cells, alvear stimulation that was too weak to excite the axon of the impaled cell elicited action potentials, which appeared to arise from transmembrane depolarizations at the soma. When subthreshold transmembrane depolarizations were superimposed on subthreshold depolarizing current pulses, somatic action potentials were generated synchronously with the antidromic population spikes. The depolarizations of pyramidal somata were finely graded with stimulus intensity, were unaffected by polarization of the membrane, and were not occluded by preceding action potentials. The laminar profile of extracellular field potentials perpendicular to the cell body layer was obtained with an array of extracellular recording locations. Numerical techniques of current source-density analysis indicated that at the peak of the somatic population spike, there was an extracellular current sink near pyramidal somata and sources in distal dendritic regions. It is concluded that during population spikes an extracellular electrical field causes currents to flow passively across inactive pyramidal cell membranes, thus depolarizing their somata. The transmembrane depolarizations associated with population spikes would tend to excite and synchronize the population of pyramidal cells.


1993 ◽  
Vol 70 (3) ◽  
pp. 961-975 ◽  
Author(s):  
S. F. Stasheff ◽  
M. Hines ◽  
W. A. Wilson

1. Intracellular and extracellular recording techniques were used to study the increase in ectopic (i.e., nonsomatic) action-potential generation occurring among CA3 pyramidal cells during the kindling-like induction of electrographic seizures (EGSs) in this subpopulation of the hippocampal slice. Kindling-like stimulus trains (60 Hz, 2 s) were delivered to s. radiatum of CA3 at 10-min intervals. As EGSs developed, the frequency of ectopic firing increased markedly (by 10.33 +/- 3.29 spikes/min, mean +/- SE, P << 0.01). Several methods were applied to determine the initiation site for these action potentials within the cell (axons vs. dendrites). 2. Collision tests were conducted between known antidromic and orthodromic action potentials in CA3 cells to determine the critical period, c, for collision. Attempts were then made to collide ectopic spikes with known antidromic action potentials. At intervals less than c, ectopic spikes failed to collide with antidromic ones, in 5 of 10 cases. In these cells, this clearly indicates that the ectopic spikes were themselves of axonal origin. In the remaining five cases, ectopic spikes collided with antidromic action potentials at intervals approximately equal to c, most likely because of interactions within the complex system of recurrent axon collaterals in CA3. 3. Action potentials of CA3 pyramidal cells were simulated with the use of a compartmental computer model, NEURON. These simulations were based on prior models of CA3 pyramidal neurons and of the motoneuron action potential. Simulated action potentials generated in axonal compartments possessed a prominent inflection on their rising phase (IS-SD break), which was difficult to appreciate in those spikes generated in somatic or dendritic compartments. 4. An analysis of action potentials recorded experimentally from CA3 pyramidal cells also showed that antidromic spikes possess a prominent IS-SD break that is not present in orthodromic spikes. In addition to identified antidromic action potentials, ectopic spikes also possess such an inflection. Together with the predictions of computer simulations, this analysis also indicates that ectopic spikes originate in the axons of CA3 cells. 5. Tetrodotoxin (TTX, 50 microM) was locally applied by pressure injection while monitoring ectopic spike activity. Localized application of TTX to regions of the slice that could include the axons but not the dendrites of recorded cells abolished or markedly reduced the frequency of ectopic spikes (n = 5), further confirming the hypothesis that these action potentials arise from CA3 axons.(ABSTRACT TRUNCATED AT 400 WORDS)


2007 ◽  
Vol 97 (1) ◽  
pp. 746-760 ◽  
Author(s):  
Yousheng Shu ◽  
Alvaro Duque ◽  
Yuguo Yu ◽  
Bilal Haider ◽  
David A. McCormick

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.


2021 ◽  
Author(s):  
Alessio Paolo Buccino ◽  
Xinyue Yuan ◽  
Vishalini Emmenegger ◽  
Xiaohan Xue ◽  
Tobias Gaenswein ◽  
...  

Neurons communicate with each other by sending action potentials through their axons. The velocity of axonal signal propagation describes how fast electrical action potentials can travel, and can be affected in a human brain by several pathologies, including multiple sclerosis, traumatic brain injury and channelopathies. High-density microelectrode arrays (HD-MEAs) provide unprecedented spatio-temporal resolution to extracellularly record neural electrical activity. The high density of the recording electrodes enables to image the activity of individual neurons down to subcellular resolution, which includes the propagation of axonal signals. However, axon reconstruction, to date, mainly relies on a manual approach to select the electrodes and channels that seemingly record the signals along a specific axon, while an automated approach to track multiple axonal branches in extracellular action-potential recordings is still missing. In this article, we propose a fully automated approach to reconstruct axons from extracellular electrical-potential landscapes, so-called "electrical footprints" of neurons. After an initial electrode and channel selection, the proposed method first constructs a graph, based on the voltage signal amplitudes and latencies. Then, the graph is interrogated to extract possible axonal branches. Finally, the axonal branches are pruned and axonal action-potential propagation velocities are computed. We first validate our method using simulated data from detailed reconstructions of neurons, showing that our approach is capable of accurately reconstructing axonal branches. We then apply the reconstruction algorithm to experimental recordings of HD-MEAs and show that it can be used to determine axonal morphologies and signal-propagation velocities at high throughput. We introduce a fully automated method to reconstruct axonal branches and estimate axonal action-potential propagation velocities using HD-MEA recordings. Our method yields highly reliable and reproducible velocity estimations, which constitute an important electrophysiological feature of neuronal preparations.


2000 ◽  
Vol 84 (3) ◽  
pp. 1404-1413 ◽  
Author(s):  
Tomoshige Koga ◽  
Robert M. Bradley

The properties of afferent sensory neurons supplying taste receptors on the tongue were examined in vitro. Neurons in the geniculate (GG) and petrosal ganglia (PG) supplying the tongue were fluorescently labeled, acutely dissociated, and then analyzed using patch-clamp recording. Measurement of the dissociated neurons revealed that PG neurons were significantly larger than GG neurons. The active and passive membrane properties of these ganglion neurons were examined and compared with each other. There were significant differences between the properties of neurons in the PG and GG ganglia. The mean membrane time constant, spike threshold, action potential half-width, and action potential decay time of GG neurons was significantly less than those of PG neurons. Neurons in the PG had action potentials that had a fast rise and fall time (sharp action potentials) as well as action potentials with a deflection or hump on the falling phase (humped action potentials), whereas action potentials of GG neurons were all sharp. There were also significant differences in the response of PG and GG neurons to the application of acetylcholine (ACh), serotonin (5HT), substance P (SP), and GABA. Whereas PG neurons responded to ACh, 5HT, SP, and GABA, GG neurons only responded to SP and GABA. In addition, the properties of GG neurons were more homogeneous than those of the PG because all the GG neurons had sharp spikes and when responses to neurotransmitters occurred, either all or most of the neurons responded. These differences between neurons of the GG and PG may relate to the type of receptor innervated. PG ganglion neurons innervate a number of receptor types on the posterior tongue and have more heterogeneous properties, while GG neurons predominantly innervate taste buds and have more homogeneous properties.


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