Rheobase

Last updated
Fig. 1 - Rheobase and chronaxie are points defined on the strength-duration curve for stimulus of an excitable tissue. Rheobase chronaxie.svg
Fig. 1 – Rheobase and chronaxie are points defined on the strength-duration curve for stimulus of an excitable tissue.

Rheobase is a measure of membrane potential excitability. In neuroscience, rheobase is the minimal current amplitude of infinite duration that results in the depolarization threshold of the cell membranes being reached, such as an action potential or the contraction of a muscle. [1] In Greek, the root rhe translates to "current or flow", and basi means "bottom or foundation": thus the rheobase is the minimum current that will produce an action potential or muscle contraction.

Contents

Rheobase can be best understood in the context of the strength-duration relationship (Fig. 1). [2] The ease with which a membrane can be stimulated depends on two variables: the strength of the stimulus, and the duration for which the stimulus is applied. [3] These variables are inversely related: as the strength of the applied current increases, the time required to stimulate the membrane decreases (and vice versa) to maintain a constant effect. [3] Mathematically, rheobase is equivalent to half the current that needs to be applied for the duration of chronaxie, which is a strength-duration time constant that corresponds to the duration of time that elicits a response when the nerve is stimulated at twice rheobasic strength. [3]

The strength-duration curve was first discovered by G. Weiss in 1901, but it was not until 1909 that Louis Lapicque coined the term rheobase. [4] Many studies are being conducted in relation to rheobase values and the dynamic changes throughout maturation and between different nerve fibers. [5] In the past strength-duration curves and rheobase determinations were used to assess nerve injury; today, they play a role in clinical identification of many neurological pathologies, including diabetic neuropathy, CIDP, Machado–Joseph disease, [6] and ALS. [7]

Strength-Duration Curve

The strength-duration time constant (chronaxie) and rheobase are parameters that describe the strength-duration curve—the curve that relates the intensity of a threshold stimulus to its duration. As the duration of a test stimulus increases, the strength of the current required to activate a single fiber action potential decreases.

The strength-duration curve is a plot of the threshold current (I) versus pulse duration (d) required to stimulate excitable tissue. [4] As mentioned, the two important points on the curve are rheobase (b) and chronaxie (c), which correlates to twice the rheobase (2b). Strength-duration curves are useful in studies where the current required is changed when the pulse duration is changed. [8]

Lapicque's Equation

In 1907, Louis Lapicque, a French neuroscientist, proposed his exponential equation for the strength-duration curve. His equation for determining current I:

where b relates to the rheobase value and c relates to the chronaxie value over duration d.

Lapicque's hyperbolic formula combines the threshold amplitude of a stimulus with its duration. This represents the first manageable with physiologically defined parameters that could compare excitability of different tissues, reflecting an urgent need at the turn of the 20th century. [4] Lapicque used constant-current, capacitor-discharge pulses to obtain chronaxie for a wide variety of excitable tissues. [4] Rheobase in the Lapicque equation is the asymptote of the hyperbolic curve at very long durations.

Weiss's Equation

In 1901, G. Weiss proposed another linear equation using a charge Q duration curve. The electrical charge Q can be calculated with the following equation:

or

again, where I is the current is measured in amperes multiplied by duration d. b relates to the rheobase value and c relates to the chronaxie value.

Rheobase in the Weiss formula is the slope of the graph. The x-intercept of the Weiss equation is equal to b x c, or rheobase times chronaxie.

This equation suggests that a graph of threshold stimulus strength versus stimulus duration should show a decay toward zero as stimulus duration is increased, so the stimulus strength required to reach threshold is predicted to increase during more protracted stimulation. [4] The strength-duration curve for a typical nerve membrane is slightly skewed from the predicted graph, in that the curve flattens out in response to repetitive stimulation reaching an asymptote representing rheobase. [4] When the duration of a stimulus is prolonged, charge transfer and membrane potential rise exponentially to a plateau (instead of increasing linearly with time). [4] [6] When rheobase exceeds the strength of the stimulus, stimulation fails to generate action potentials (even with large values of t); thus if the stimulus is too small, the membrane potential never reaches threshold. The disparity between the shape of the strength-duration curve predicted by Weiss's equation and the one actually observed in neural membranes can be attributed to leakage of charge that occurs under physiological conditions, a feature of the electrical resistance of the membrane. [4] [6] Weiss' equation predicts the relationship between stimulus strength and duration for an ideal capacitor with no leakage resistance.

Despite this limitation, Weiss’s equation provides the best fit for strength-duration data and indicates that rheobase and time constant (chronaxie) can be measured from the charge duration curve with a very small margin of error. [9] Weiss used rectangular, constant-current pulses and found that threshold charge required for stimulation increased linearly with pulse duration. [4] He also found that stimulus charge, the product of stimulus current and stimulus duration is proportional to rheobase, so that only two stimulus durations are necessary to calculate rheobase. [6]

Measurement

The use of strength-duration curves was developed in the 1930s, followed by the use of threshold current measurements for the study of human axonal excitability in the 1970s. [6] Use of these methods in toxic neuropathies has enabled researchers to designate protective factors for many peripheral nerve disorders, and several diseases of the central nervous system (see Clinical Significance).

Nerve excitability examination complements conventional nerve conduction studies by allowing insight into biophysical characteristics of axons, as well as their ion-channel functioning. [10] The protocol is aimed at providing information about nodal as well as internodal ion channels, and the indices are extremely sensitive to axon membrane potential. [10] These studies have provided insight into conditions characterized by changes in resting potential, such as electrolyte concentration and pH, as well as specific ion-channel and pump function in normal and diseased nerves. [11] Furthermore, software programs enabling the calculation of rheobasic and time constant values from both normal and diseased nerves have recently enabled researchers to pinpoint some important factors for a number of pervasive nerve disorders, many of which involve substantial demyelination (see Clinical Significance). [10] [11] Supraximal electrical stimulation and measurement of conduction velocity and amplitudes of compound motor (CMAP) and sensory (SNAP) responses provide measures of the number and conduction velocities of large myelinated fibers. [10] [11] Additionally, multiple measures of excitability in the TROND protocol permit assessment of ion channels (transient and persistent Na+ channels, slow K+ channels) at nodes of Ranvier by computing stimulus response curves, strength duration time constant (chronaxie), rheobase, and the recovery cycle after passage of an action potential. [10] This is accomplished by applying long polarizing currents to the nerve and measuring the influence of voltage on voltage gated-ion channels beneath myelin. [10]

In Neurons

In neurons, the rheobase is defined as the smallest injected step current, of infinite duration, that results in one action potential. In practice, there are several challenges of measuring the rheobase. The general protocol is to inject currents of various amplitudes, observe if any action potentials were produced, and then further refine the injected current magnitude until the boundary between spiking and non-spiking behavior is identified.

Duration

Because it is not possible to wait an infinite amount of time, trial currents are injected for finite durations. The current duration varies among publications, but is on the order of 0.1-5 seconds. However, this also implies that an injected current that did not result in spikes could have resulted in spikes if the duration was longer. For this reason, the current duration should be specified when reporting a cell's rheobase.

Precision

In addition to current duration, it is not possible to find the exact rheobase value in a real cell. In publications, a common method is to try various currents at some increments (e.g. 10 pA), and find the two consecutive current amplitudes that do and do not result in action potentials. The smallest difference between the lower and upper currents used is the rheobase search precision: the "true" rheobase is somewhere between the two tested current values.

Precision is also affected by thermal noise and stochastic nature of ion channels. If a cell does not reliably spike at a certain current amplitude, the search method could be modified to include multiple repeated current injections to find such current that reliably results in spikes.

Maximum Current Amplitude Range

When searching for the rheobase, a proper current amplitude range must be chosen. If the maximum current used is too small, no spikes will be produced. If too large, cell health might be compromised. Before starting the search, the cell's membrane input resistance (from negative current injections) can be measured and used to estimate the current necessary to activate the cell (e.g. if -10pA reduces the potential by 20mV, then a cell that rests at -60mV will likely spike at least once in response to +30pA injections).

Negative Rheobase

The standard rheobase definition assumes that a given cell does not spike when a current is not injected. However, some cells are spontaneously spiking (e.g. Cardiac pacemaker cells). For such cells, a negative (inhibitory) current will quiet them, while a slightly less negative current will result in action potentials. In such cases, stimulation protocols that utilize the rheobase and assume that spiking rates are proportional to the rheobase will produce nonsense results (e.g. spike rate in response to 2X rheobase will not be greater than at 1.5X rheobase).

Bursting cells

Bursting cells will produce multiple spikes once activated. For such cells, it can be very difficult to find the current that produces only a single spike within a given time frame. For such cells, finding the boundary between currents that result in bursts and no bursts could be used.

Cells with Sub-threshold Oscillations

Cells that exhibit sub-threshold oscillations will exhibit phase-dependent rheobase. If the current step onset co-insides with the peak of a sub-threshold oscillation (cell is closer to the firing threshold), a smaller current will be needed to elicit a spike. Conversely, if the step onset co-insides with the trough of the oscillation (further away from the threshold), a larger current will be necessary to produce a spike. Using different delays before onset and repeating the current injections can be used to find the current that will guarantee that a spike will be produced regardless of sub-threshold oscillation phase.

Temperature

Slice temperature can affect ion channel kinetics and alter the rheobase. This means that a current that produces one spike under one temperature, might not produce any spikes under a different temperature. For this reason, the slice temperature should be specified when reporting a cell's rheobase.

Neurobiological significance

The properties of the nodal membrane largely determine the axon's strength-duration properties, and these will change with changes in membrane potential, with temperature, and with demyelination as the exposed membrane is effectively enlarged by the inclusion of paranodal and intermodal membrane. [9] Thus, the strength-duration time constant is a reflection of persistent Na+ channel function, and is furthermore influenced by membrane potential and passive membrane properties. [10] As such, many aspects of nerve excitability testing depend on sodium channel functions: namely, the strength-duration time constant, the recovery cycle, the stimulus-response curve, and the current-threshold relationship. Measuring responses in nerve that are related to nodal function (including strength-duration time constant and rheobase) and internodal function has allowed insight into normal axon physiology as well as normal fluctuations of electrolyte concentrations. [7]

Rheobase is influenced by excitability of the nodal membrane, which increases with hyperpolarization and decreases with depolarization. Its voltage-dependence follows the behavior of persistent sodium channels that are active near threshold and have rapidly activating, slowly inactivating channel properties. [6] Depolarization increases the Na+ current through the persistent channels, resulting in a lower rheobase; hyperpolarization has the opposite effect. The strength-duration time constant increases with demyelination, as the exposed membrane is enlarged by inclusion of paranodal and internodal membrane. The function of the latter of these is to maintain resting membrane potential, so internodal dysfunction significantly affects excitability in a diseased nerve. Such implications are further discussed in Clinical Significance.

Sensory nerves vs. motor nerves

Nerve excitability studies have established a number of biophysical differences between human sensory and motor axons. [6] Even though the diameters and conduction velocities of the most excitable motor and sensory fibers are similar, sensory fibers have significantly longer strength-duration time constants. [11] As a result, sensory nerves have a longer strength-duration time constant and a lower rheobase than motor nerves. [7]

Many studies have suggested that differences in the expression of threshold channels could account for the sensory-motor differences in strength-duration time constant. [11] The differences in strength-duration time constant and rheobase of normal sensory and motor axons are thought to reflect differences in expression of a persistent Na+ conductance. [12] Additionally, sensory axons accommodate more to long-lasting hyperpolarizing currents than do motor axons, suggesting a greater expression of the hyperpolarization-activated inward rectifier channels. [12] Finally, the electrogenic Na+/K+-ATPase is more active in sensory nerves, which have a greater dependence on this pump to maintain resting membrane potential than do motor nerves. [6]

Increases in the strength-duration time constant are observed when this conductance is activated by depolarization, or by hyperventilation. [7] However, demyelination, which exposes internodal membrane with a higher membrane time constant than that of the original node, can also increase strength-duration time constant. [13]

The strength-duration time constant of both cutaneous and motor afferents decreases with age, and this corresponds to an increase in rheobase. [7] Two possible reasons for this age-related decrease in the strength-duration time constant have been proposed. First, nerve geometry might change with age because of axonal loss and neural fibrosis. Secondly, the persistent Na+ conductance might decrease maturation. Significant decreases in threshold for sensory and motor fibers have been observed during ischemia. [7] These decreases in threshold were furthermore associated with significant increases in the strength-duration time constant, appreciably indicating a significant decrease in rheobase current. These changes are thought to be the result of non-inactivating, voltage-dependent Na+ channels, which are active at resting potential.

Clinical significance

Axonal degeneration and regeneration are common processes in many nerve disorders. [10] As a consequence of myelin remodeling, the internodal length is known to remain persistently short. [10] Little is known about how neurons cope with the increased number of nodes except that there may be a compensatory increase in Na+ channels so that the internodal density is restored. [6] Nevertheless, most extant research findings maintain that regenerated axons may be functionally deficient, as the access to the K+ channel under the paranodal myelin may be increased. [6] [10]

In the clinical setting, the function of the internode can only be explored by excitability studies (see Measurement). Experimental observations utilizing threshold measurements to assess excitability of myelinated nerve fibers have indicated that the function of regenerated internodes indeed remains persistently abnormal, with regenerated motor axons displaying increased rheobase and decreased chronaxie—changes that are consistent with abnormal active membrane properties. [10] These studies have furthermore determined that activity-dependent conduction block in myelination was due to hyperpolarization, as well as abnormally increased Na+ currents and increased availability of fast K+ rectifiers. [10] Listed below are findings on the changes in nerve excitability, and therefore the strength-duration time constant, that have been observed within several of the most pervasive nerve disorders.

Amyotrophic lateral sclerosis

Amyotrophic lateral sclerosis (ALS) affects upper and lower motor systems, with symptoms ranging from muscle atrophy, hyperreflexia, and fasciculations, all of which suggest increased axonal excitability. [7] Many studies have concluded that abnormally decreased K+ conductance results in axonal depolarization, leading to axonal hyperexcitability and the generation of fasciculation. [6] [7] ALS patients in these studies demonstrated longer strength-duration time constants and lower values for rheobase than in control subjects. [6] [7]

Another study has demonstrated that sensory rheobases were no different in patients from those in age-matched control subjects, whereas motor rheobases were significantly lower. [7] Discovering that motor axons have both a lower rheobase and a longer strength-duration time constant in ALS has prompted the conclusion that motor neurons are abnormally excitable in ALS, with properties more like those of sensory neurons. [7] Changes in the geometry of the nerve due to loss of axons within the peripheral nerve likely cause this shift in rheobase. [7] A logical conclusion of the present data is that there is a greater persistent Na+ conductance at rest in motor axons of patients with ALS than normal. [7]

Machado–Joseph disease

Machado–Joseph disease (MJD) is a triplet repeat disease characterized by cerebellar ataxia, pyramidal signs, ophthalmoplegia, and polyneuropathy. [6] Since muscle cramps are a frequent occurrence in MJD, axonal hyperexcitability has been considered to play a role in the disease. [6] [10] Research has demonstrated that the strength-duration time constant in MJD patients is significantly longer than in controls, and this corresponds to a significant reduction in rheobase. [6] [10] Combined with findings on Na+ channel blockers, these data suggest that the cramps in MJD are likely caused by the increased persistent Na+ channel conductance that may be unregulated during axonal reinnervation (which results from long-term axonal degeneration). [6] [10]

Diabetic polyneuropathy

The hallmark feature of diabetic polyneuropathy is a blend of axonal and demyelinating damage, which results from mechanical demyelination and channel/pump dysfunctions. [6] Diabetic patients have been found to experience a significantly shorter strength-duration time constant and a much higher rheobase than normal patients. [6]

Measurement of sensory conduction in distal nerve segments have shown salient defects in diabetic patients, suggesting that the function of persistent Na+ channels is decreased in diabetics. [6] These experiments have furthermore opened new avenues for preventative drug efficacy. Measurement of chronaxie and rheobase in sural sensory fibers has revealed mild reductions in excitability in diabetics, as evidenced by significant reductions in conduction velocity and chronaxie of sensory fibers with corresponding increases in rheobase. [6] These effects are attributed to the reduced Na+-K+-ATPase activity in axon of diabetic patients, which causes Na+ ions to accumulation intracellularly, as well as a subsequent a decrease in the transmembrane Na+ gradient. [6]

Charcot–Marie–Tooth disease

Charcot–Marie–Tooth disease (CMT) is the most common form of hereditary neuropathy and can be further subdivided into two types: Type 1: demyelinating, and Type 2: axonal. [6] Measurement of chronaxie and rheobase for these diseased nerves has concluded that electrophysiologically, a patient with demyelinating (Type I) CMT demonstrates slow nerve conduction velocity, frequently accompanied by reduced amplitudes of motor and sensory action potentials; moreover, axonal (Type II) CMT can be attributed to impaired interaction between Schwann cells and axons. [6] [10] Changes in excitability measures are typically universal and vary little between patients, and this is likely due to the diffuse distribution of demyelination, suggesting changed cable properties associated with short internodes. [10]

Multifocal motor neuropathy

Multifocal motor neuropathy (MMN) is a rare clinical case, characterized almost entirely by muscle weakness, atrophy, and fasciculations. [6] An important feature of MMN is that the strength-duration constant is significantly small, corresponding to an appreciable increase in rheobase. [6] Both measurements have been shown to become normalized following intravenous immunoglobulin therapy. [6]

Chronic inflammatory demyelinating polyneuropathy

Chronic inflammatory demyelinating polyneuropathy (CIDP) is an immunological demyelinating polyneuropathy. [6] [10] As a result of increased paranodal capacitance from demyelination, patients experience increased stimulation threshold, shorter strength-duration time constant, and increased rheobase. [6] [10]

See also

Related Research Articles

<span class="mw-page-title-main">Axon</span> Long projection on a neuron that conducts signals to other neurons

An axon or nerve fiber is a long, slender projection of a nerve cell, or neuron, in vertebrates, that typically conducts electrical impulses known as action potentials away from the nerve cell body. The function of the axon is to transmit information to different neurons, muscles, and glands. In certain sensory neurons, such as those for touch and warmth, the axons are called afferent nerve fibers and the electrical impulse travels along these from the periphery to the cell body and from the cell body to the spinal cord along another branch of the same axon. Axon dysfunction can be the cause of many inherited and acquired neurological disorders that affect both the peripheral and central neurons. Nerve fibers are classed into three types – group A nerve fibers, group B nerve fibers, and group C nerve fibers. Groups A and B are myelinated, and group C are unmyelinated. These groups include both sensory fibers and motor fibers. Another classification groups only the sensory fibers as Type I, Type II, Type III, and Type IV.

In neuroscience, an F wave is one of several motor responses which may follow the direct motor response (M) evoked by electrical stimulation of peripheral motor or mixed nerves. F-waves are the second of two late voltage changes observed after stimulation is applied to the skin surface above the distal region of a nerve, in addition to the H-reflex which is a muscle reaction in response to electrical stimulation of innervating sensory fibers. Traversal of F-waves along the entire length of peripheral nerves between the spinal cord and muscle, allows for assessment of motor nerve conduction between distal stimulation sites in the arm and leg, and related motoneurons (MN's) in the cervical and lumbosacral cord. F-waves are able to assess both afferent and efferent loops of the alpha motor neuron in its entirety. As such, various properties of F-wave motor nerve conduction are analyzed in nerve conduction studies (NCS), and often used to assess polyneuropathies, resulting from states of neuronal demyelination and loss of peripheral axonal integrity.

<span class="mw-page-title-main">Myelin</span> Fatty substance that surrounds nerve cell axons to insulate them and increase transmission speed

Myelin is a lipid-rich material that surrounds nerve cell axons to insulate them and increase the rate at which electrical impulses pass along the axon. The myelinated axon can be likened to an electrical wire with insulating material (myelin) around it. However, unlike the plastic covering on an electrical wire, myelin does not form a single long sheath over the entire length of the axon. Rather, myelin ensheaths the axon segmentally: in general, each axon is encased in multiple long sheaths with short gaps between, called nodes of Ranvier. At the nodes of Ranvier, which are approximately one thousandth of a mm in length, the axon's membrane is bare of myelin.

<span class="mw-page-title-main">Neuron</span> Electrically excitable cell found in the nervous system of animals

Within a nervous system, a neuron, neurone, or nerve cell is an electrically excitable cell that fires electric signals called action potentials across a neural network. Neurons communicate with other cells via synapses, which are specialized connections that commonly use minute amounts of chemical neurotransmitters to pass the electric signal from the presynaptic neuron to the target cell through the synaptic gap.

<span class="mw-page-title-main">Action potential</span> Neuron communication by electric impulses

An action potential occurs when the membrane potential of a specific cell rapidly rises and falls. This depolarization then causes adjacent locations to similarly depolarize. Action potentials occur in several types of animal cells, called excitable cells, which include neurons, muscle cells, and in some plant cells. Certain endocrine cells such as pancreatic beta cells, and certain cells of the anterior pituitary gland are also excitable cells.

<span class="mw-page-title-main">Refractory period (physiology)</span> Period of time after an organism performs an action before it is possible to perform again

Refractoriness is the fundamental property of any object of autowave nature not responding to stimuli, if the object stays in the specific refractory state. In common sense, refractory period is the characteristic recovery time, a period that is associated with the motion of the image point on the left branch of the isocline .

<span class="mw-page-title-main">Stimulus (physiology)</span> Detectable change in the internal or external surroundings

In physiology, a stimulus is a detectable change in the physical or chemical structure of an organism's internal or external environment. The ability of an organism or organ to detect external stimuli, so that an appropriate reaction can be made, is called sensitivity (excitability). Sensory receptors can receive information from outside the body, as in touch receptors found in the skin or light receptors in the eye, as well as from inside the body, as in chemoreceptors and mechanoreceptors. When a stimulus is detected by a sensory receptor, it can elicit a reflex via stimulus transduction. An internal stimulus is often the first component of a homeostatic control system. External stimuli are capable of producing systemic responses throughout the body, as in the fight-or-flight response. In order for a stimulus to be detected with high probability, its level of strength must exceed the absolute threshold; if a signal does reach threshold, the information is transmitted to the central nervous system (CNS), where it is integrated and a decision on how to react is made. Although stimuli commonly cause the body to respond, it is the CNS that finally determines whether a signal causes a reaction or not.

<span class="mw-page-title-main">Threshold potential</span> Critical potential value

In electrophysiology, the threshold potential is the critical level to which a membrane potential must be depolarized to initiate an action potential. In neuroscience, threshold potentials are necessary to regulate and propagate signaling in both the central nervous system (CNS) and the peripheral nervous system (PNS).

<span class="mw-page-title-main">Node of Ranvier</span> Gaps between myelin sheaths on the axon of a neuron

In neuroscience and anatomy, nodes of Ranvier, also known as myelin-sheath gaps, occur along a myelinated axon where the axolemma is exposed to the extracellular space. Nodes of Ranvier are uninsulated and highly enriched in ion channels, allowing them to participate in the exchange of ions required to regenerate the action potential. Nerve conduction in myelinated axons is referred to as saltatory conduction due to the manner in which the action potential seems to "jump" from one node to the next along the axon. This results in faster conduction of the action potential.

<span class="mw-page-title-main">End-plate potential</span>

End plate potentials (EPPs) are the voltages which cause depolarization of skeletal muscle fibers caused by neurotransmitters binding to the postsynaptic membrane in the neuromuscular junction. They are called "end plates" because the postsynaptic terminals of muscle fibers have a large, saucer-like appearance. When an action potential reaches the axon terminal of a motor neuron, vesicles carrying neurotransmitters are exocytosed and the contents are released into the neuromuscular junction. These neurotransmitters bind to receptors on the postsynaptic membrane and lead to its depolarization. In the absence of an action potential, acetylcholine vesicles spontaneously leak into the neuromuscular junction and cause very small depolarizations in the postsynaptic membrane. This small response (~0.4mV) is called a miniature end plate potential (MEPP) and is generated by one acetylcholine-containing vesicle. It represents the smallest possible depolarization which can be induced in a muscle.

Pulpitis is inflammation of dental pulp tissue. The pulp contains the blood vessels, the nerves, and connective tissue inside a tooth and provides the tooth's blood and nutrients. Pulpitis is mainly caused by bacterial infection which itself is a secondary development of caries. It manifests itself in the form of a toothache.

<span class="mw-page-title-main">Chronaxie</span> Electrophysiology metric

Chronaxie is the minimum time required for an electric current double the strength of the rheobase to stimulate a muscle or a neuron. Rheobase is the lowest intensity with indefinite pulse duration which just stimulated muscles or nerves. Chronaxie is dependent on the density of voltage-gated sodium channels in the cell, which affect that cell’s excitability. Chronaxie varies across different types of tissue: fast-twitch muscles have a lower chronaxie, slow-twitch muscles have a higher one. Chronaxie is the tissue-excitability parameter that permits choice of the optimum stimulus pulse duration for stimulation of any excitable tissue. Chronaxie (c) is the Lapicque descriptor of the stimulus pulse duration for a current of twice rheobasic (b) strength, which is the threshold current for an infinitely long-duration stimulus pulse. Lapicque showed that these two quantities (c,b) define the strength-duration curve for current: I = b(1+c/d), where d is the pulse duration. However, there are two other electrical parameters used to describe a stimulus: energy and charge. The minimum energy occurs with a pulse duration equal to chronaxie. Minimum charge (bc) occurs with an infinitely short-duration pulse. Choice of a pulse duration equal to 10c requires a current of only 10% above rheobase (b). Choice of a pulse duration of 0.1c requires a charge of 10% above the minimum charge (bc).

In physiology, the all-or-none law is the principle that if a single nerve fibre is stimulated, it will always give a maximal response and produce an electrical impulse of a single amplitude. If the intensity or duration of the stimulus is increased, the height of the impulse will remain the same. The nerve fibre either gives a maximal response or none at all.

<span class="mw-page-title-main">Group C nerve fiber</span> One of three classes of nerve fiber in the central nervous system and peripheral nervous system

Group C nerve fibers are one of three classes of nerve fiber in the central nervous system (CNS) and peripheral nervous system (PNS). The C group fibers are unmyelinated and have a small diameter and low conduction velocity, whereas Groups A and B are myelinated. Group C fibers include postganglionic fibers in the autonomic nervous system (ANS), and nerve fibers at the dorsal roots. These fibers carry sensory information.

<span class="mw-page-title-main">SCN8A</span> Protein-coding gene in the species Homo sapiens

Sodium channel protein type 8 subunit alpha also known as Nav1.6 is a membrane protein encoded by the SCN8A gene. Nav1.6 is one sodium channel isoform and is the primary voltage-gated sodium channel at each node of Ranvier. The channels are highly concentrated in sensory and motor axons in the peripheral nervous system and cluster at the nodes in the central nervous system.

<span class="mw-page-title-main">Dendritic spike</span> Action potential generated in the dendrite of a neuron

In neurophysiology, a dendritic spike refers to an action potential generated in the dendrite of a neuron. Dendrites are branched extensions of a neuron. They receive electrical signals emitted from projecting neurons and transfer these signals to the cell body, or soma. Dendritic signaling has traditionally been viewed as a passive mode of electrical signaling. Unlike its axon counterpart which can generate signals through action potentials, dendrites were believed to only have the ability to propagate electrical signals by physical means: changes in conductance, length, cross sectional area, etc. However, the existence of dendritic spikes was proposed and demonstrated by W. Alden Spencer, Eric Kandel, Rodolfo Llinás and coworkers in the 1960s and a large body of evidence now makes it clear that dendrites are active neuronal structures. Dendrites contain voltage-gated ion channels giving them the ability to generate action potentials. Dendritic spikes have been recorded in numerous types of neurons in the brain and are thought to have great implications in neuronal communication, memory, and learning. They are one of the major factors in long-term potentiation.

<span class="mw-page-title-main">Summation (neurophysiology)</span>

Summation, which includes both spatial summation and temporal summation, is the process that determines whether or not an action potential will be generated by the combined effects of excitatory and inhibitory signals, both from multiple simultaneous inputs, and from repeated inputs. Depending on the sum total of many individual inputs, summation may or may not reach the threshold voltage to trigger an action potential.

<span class="mw-page-title-main">Nonsynaptic plasticity</span> Form of neuroplasticity

Nonsynaptic plasticity is a form of neuroplasticity that involves modification of ion channel function in the axon, dendrites, and cell body that results in specific changes in the integration of excitatory postsynaptic potentials and inhibitory postsynaptic potentials. Nonsynaptic plasticity is a modification of the intrinsic excitability of the neuron. It interacts with synaptic plasticity, but it is considered a separate entity from synaptic plasticity. Intrinsic modification of the electrical properties of neurons plays a role in many aspects of plasticity from homeostatic plasticity to learning and memory itself. Nonsynaptic plasticity affects synaptic integration, subthreshold propagation, spike generation, and other fundamental mechanisms of neurons at the cellular level. These individual neuronal alterations can result in changes in higher brain function, especially learning and memory. However, as an emerging field in neuroscience, much of the knowledge about nonsynaptic plasticity is uncertain and still requires further investigation to better define its role in brain function and behavior.

A depolarizing prepulse (DPP) is an electrical stimulus that causes the potential difference measured across a neuronal membrane to become more positive or less negative, and precedes another electrical stimulus. DPPs may be of either the voltage or current stimulus variety and have been used to inhibit neural activity, selectively excite neurons, and increase the pain threshold associated with electrocutaneous stimulation.

Neural accommodation or neuronal accommodation occurs when a neuron or muscle cell is depolarised by slowly rising current in vitro. The Hodgkin–Huxley model also shows accommodation. Sudden depolarisation of a nerve evokes propagated action potential by activating voltage-gated fast sodium channels incorporated in the cell membrane if the depolarisation is strong enough to reach threshold. The open sodium channels allow more sodium ions to flow into the cell and resulting in further depolarisation, which will subsequently open even more sodium channels. At a certain moment this process becomes regenerative and results in the rapid ascending phase of action potential. In parallel with the depolarisation and sodium channel activation, the inactivation process of the sodium channels is also driven by depolarisation. Since the inactivation is much slower than the activation process, during the regenerative phase of action potential, inactivation is unable to prevent the "chain reaction"-like rapid increase in the membrane voltage.

References

  1. Ashley, et al. "Determination of the Chronaxie and Rheobase of Denervated Limb Muscles in Conscious Rabbits". Artificial Organs, Volume 29 Issue 3 Page 212 - March 2005
  2. Fleshman et al. "Rheobase, input resistance, and motor-unit type in medial gastrocnemius motoneurons in the cat." Journal of Neurophysiology, 1981.
  3. 1 2 3 Boinagrov, D., et al. (2010). "Strength-duration relationship for extracellular neural stimulation: Numerical and analytical models". Journal of Neurophysiology, 194(2010), 2236–2248.
  4. 1 2 3 4 5 6 7 8 9 Geddes, L. A. (2004). "Accuracy limitations of chronaxie values". IEEE Transactions on Biomedical Engineering, 51(1).
  5. Carrascal, et al. (2005). "Changes during postnatal development in physiological and anatomical characteristics of rat motoneurons studied in vitro". Brain Research Reviews, 49(2005), 377–387.
  6. 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 Nodera, H., & Kaji, R. (2006). "Nerve excitability testing in its clinical application to neuromuscular diseases". Clinical Neurophysiology, 117(2006), 1902–1916.
  7. 1 2 3 4 5 6 7 8 9 10 11 12 13 Mogyoros, I., et al. (1998). "Strength-duration properties of sensory and motor axons in amyotrophic lateral sclerosis". Brain, 121(1998), 851–859.
  8. Geddes, L.A., & Bourland, J. D. (1985) "The Strength-Duration Curve". IEEE Transactions on Biomedical Engineering, 32 (6). 458–459.
  9. 1 2 Mogyoros, I., et al. (1995). "Strength-duration properties of human peripheral nerve". Brain, 119(1996), 439–447.
  10. 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 Krarup, C., & Mihai, M. (2009). "Nerve conduction and excitability studies in peripheral nerve disorders". Current Opinion in Neurology, 22(5), 460–466.
  11. 1 2 3 4 5 Mogyoros, I. et al. (1997). "Excitability changes in human sensory and motor axons during hyperventilation and ischaemia”. ‘’Brain’’ (1997), 120, 317–325.
  12. 1 2 Bostock H. & Rockwell J. C. (1997) "Latent addition in motor and sensory fibres of human peripheral nerve". J Physiol (Lond) 1997; 498: 277–94.
  13. Bostock, H., et al. (1983) "The spatial distribution of excitability and membrane current in normal and demyelinated mammalian nerve fibers". The Journal of Physiology. (341) 41–58.