Threshold potential

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A. A schematic view of an idealized action potential illustrates its various phases as the action potential passes a point on a cell membrane. B. Actual recordings of action potentials are often distorted compared to the schematic view because of variations in electrophysiological techniques used to make the recording. Action potential vert.png
A. A schematic view of an idealized action potential illustrates its various phases as the action potential passes a point on a cell membrane. B. Actual recordings of action potentials are often distorted compared to the schematic view because of variations in electrophysiological techniques used to make the recording.

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).

Electrophysiology Study of the electrical properties of biological cells and tissues.

Electrophysiology is the branch of physiology that studies the electrical properties of biological cells and tissues. It involves measurements of voltage changes or electric current or manipulations on a wide variety of scales from single ion channel proteins to whole organs like the heart. In neuroscience, it includes measurements of the electrical activity of neurons, and, in particular, action potential activity. Recordings of large-scale electric signals from the nervous system, such as electroencephalography, may also be referred to as electrophysiological recordings. They are useful for electrodiagnosis and monitoring.

Membrane potential physical quantity

Membrane potential is the difference in electric potential between the interior and the exterior of a biological cell. With respect to the exterior of the cell, typical values of membrane potential, normally given in millivolts, range from –40 mV to –80 mV.

Depolarization change in a cells electric charge distribution

In biology, depolarization is a change within a cell, during which the cell undergoes a shift in electric charge distribution, resulting in less negative charge inside the cell. Depolarization is essential to the function of many cells, communication between cells, and the overall physiology of an organism.


Most often, the threshold potential is a membrane potential value between –50 and –55 mV, [1] but can vary based upon several factors. A neuron's resting membrane potential (–70 mV) can be altered to either increase or decrease likelihood of reaching threshold via sodium and potassium ions. An influx of sodium into the cell through open, voltage-gated sodium channels can depolarize the membrane past threshold and thus excite it while an efflux of potassium or influx of chloride can hyperpolarize the cell and thus inhibit threshold from being reached.

Volt SI derived unit of voltage

The volt is the derived unit for electric potential, electric potential difference (voltage), and electromotive force. It is named after the Italian physicist Alessandro Volta (1745–1827).

Neuron electrically excitable cell

A neuron, also known as a neurone or nerve cell, is an electrically excitable cell that communicates with other cells via specialized connections called synapses. It is the main component of nervous tissue. All animals except sponges and placozoans have neurons, but other multicellular organisms such as plants do not.

Sodium Chemical element with atomic number 11

Sodium is a chemical element with the symbol Na (from Latin natrium) and atomic number 11. It is a soft, silvery-white, highly reactive metal. Sodium is an alkali metal, being in group 1 of the periodic table, because it has a single electron in its outer shell, which it readily donates, creating a positively charged ion—the Na+ cation. Its only stable isotope is 23Na. The free metal does not occur in nature, and must be prepared from compounds. Sodium is the sixth most abundant element in the Earth's crust and exists in numerous minerals such as feldspars, sodalite, and rock salt (NaCl). Many salts of sodium are highly water-soluble: sodium ions have been leached by the action of water from the Earth's minerals over eons, and thus sodium and chlorine are the most common dissolved elements by weight in the oceans.


Initial experiments revolved around the concept that any electrical change that is brought about in neurons must occur through the action of ions. The German physical chemist Walther Nernst applied this concept in experiments to discover nervous excitability, and concluded that the local excitatory process through a semi-permeable membrane depends upon the ionic concentration. Also, ion concentration was shown to be the limiting factor in excitation. If the proper concentration of ions was attained, excitation would certainly occur. [2] This was the basis for discovering the threshold value.

Walther Nernst German physical chemist and physicist

Walther Hermann Nernst, was a German chemist known for his work in thermodynamics, physical chemistry, electrochemistry, and solid state physics. His formulation of the Nernst heat theorem helped pave the way for the third law of thermodynamics, for which he won the 1920 Nobel Prize in Chemistry. He is also known for developing the Nernst equation in 1887.

Along with reconstructing the action potential in the 1950s, Alan Lloyd Hodgkin and Andrew Huxley were also able to experimentally determine the mechanism behind the threshold for excitation. It is known as the Hodgkin–Huxley model. Through use of voltage clamp techniques on a squid giant axon, they discovered that excitable tissues generally exhibit the phenomenon that a certain membrane potential must be reached in order to fire an action potential. Since the experiment yielded results through the observation of ionic conductance changes, Hodgkin and Huxley used these terms to discuss the threshold potential. They initially suggested that there must be a discontinuity in the conductance of either sodium or potassium, but in reality both conductances tended to vary smoothly along with the membrane potential. [3]

Action potential A process in which membrane potential cycles through a depolarizing spike, triggered in response to depolarization above some threshold, followed by repolarization. This cycle is driven by the flow of ions through various voltage gated channels with

In physiology, an action potential occurs when the membrane potential of a specific cell location rapidly rises and falls: this depolarisation then causes adjacent locations to similarly depolarise. Action potentials occur in several types of animal cells, called excitable cells, which include neurons, muscle cells, endocrine cells, glomus cells, and in some plant cells.

Alan Lloyd Hodgkin physiologist and biophysicist

Sir Alan Lloyd Hodgkin was an English physiologist and biophysicist, who shared the 1963 Nobel Prize in Physiology or Medicine with Andrew Huxley and John Eccles.

Andrew Huxley English physiologist and biophysicist

Sir Andrew Fielding Huxley was an English physiologist and biophysicist. He was born into the prominent Huxley family. After graduating from Westminster School in Central London, from where he won a scholarship to Trinity College, Cambridge, he joined Alan Lloyd Hodgkin to study nerve impulses. Their eventual discovery of the basis for propagation of nerve impulses earned them the Nobel Prize in Physiology or Medicine in 1963. They made their discovery from the giant axon of the Atlantic squid. Soon after the outbreak of the Second World War, Huxley was recruited by the British Anti-Aircraft Command and later transferred to the Admiralty. After the war he resumed research at The University of Cambridge, where he developed interference microscopy that would be suitable for studying muscle fibres.

They soon discovered that at threshold potential, the inward and outward currents, of sodium and potassium ions respectively, were exactly equal and opposite. As opposed to the resting membrane potential, the threshold potential's conditions exhibited a balance of currents that were unstable. Instability refers to the fact that any further depolarization activates even more voltage-gated sodium channels, and the incoming sodium depolarizing current overcomes the delayed outward current of potassium. [4] At resting level, on the other hand, the potassium and sodium currents are equal and opposite in a stable manner, where a sudden, continuous flow of ions should not result. The basis is that at a certain level of depolarization, when the currents are equal and opposite in an unstable manner, any further entry of positive charge generates an action potential. This specific value of depolarization (in mV) is otherwise known as the threshold potential.

Resting potential the relatively static membrane potential of quiescent cells

The relatively static membrane potential of quiescent cells is called the resting membrane potential, as opposed to the specific dynamic electrochemical phenomena called action potential and graded membrane potential.

Physiological function and characteristics

The threshold value controls whether or not the incoming stimuli are sufficient to generate an action potential. It relies on a balance of incoming inhibitory and excitatory stimuli. The potentials generated by the stimuli are additive, and they may reach threshold depending on their frequency and amplitude. Normal functioning of the central nervous system entails a summation of synaptic inputs made largely onto a neuron's dendritic tree. These local graded potentials, which are primarily associated with external stimuli, reach the axon initial segment and build until they manage to reach the threshold value. [5] The larger the stimulus, the greater the depolarization, or attempt to reach threshold. The task of depolarization requires several key steps that rely on anatomical factors of the cell. The ion conductances involved depend on the membrane potential and also the time after the membrane potential changes. [6]

Central nervous system part of the nervous system consisting of the brain and spinal cord

The central nervous system (CNS) is the part of the nervous system consisting of the brain and spinal cord. The CNS is so named because it integrates the received information and coordinates and influences the activity of all parts of the bodies of bilaterally symmetric animals—that is, all multicellular animals except sponges and radially symmetric animals such as jellyfish—and it contains the majority of the nervous system. Many consider the retina and the optic nerve, as well as the olfactory nerves and olfactory epithelium as parts of the CNS, synapsing directly on brain tissue without intermediate ganglia. As such, the olfactory epithelium is the only central nervous tissue in direct contact with the environment, which opens up for therapeutic treatments. The CNS is contained within the dorsal body cavity, with the brain housed in the cranial cavity and the spinal cord in the spinal canal. In vertebrates, the brain is protected by the skull, while the spinal cord is protected by the vertebrae. The brain and spinal cord are both enclosed in the meninges. Within the CNS, the interneuronal space is filled with a large amount of supporting non-nervous cells called neuroglial cells.

Resting membrane potential

The phospholipid bilayer of the cell membrane is, in itself, highly impermeable to ions. The complete structure of the cell membrane includes many proteins that are embedded in or completely cross the lipid bilayer. Some of those proteins allow for the highly specific passage of ions, ion channels. Leak potassium channels allow potassium to flow through the membrane in response to the disparity in concentrations of potassium inside (high concentration) and outside the cell (low). The loss of positive(+) charges of the potassium(K+) ions from the inside of the cell results in a negative potential there compared to the extracellular surface of the membrane. [7] A much smaller "leak" of sodium(Na+) into the cell results in the actual resting potential, about –70 mV, being less negative than the calculated potential for K+ alone, the equilibrium potential, about –90 mV. [7] The sodium-potassium ATPase is an active transporter within the membrane that pumps potassium (2 ions) back into the cell and sodium (3 ions) out of the cell, maintaining the concentrations of both ions as well as preserving the voltage polarization.


However, once a stimulus activates the voltage-gated sodium channels to open, positive sodium ions flood into the cell and the voltage increases. This process can also be initiated by ligand or neurotransmitter binding to a ligand-gated channel. More sodium is outside the cell relative to the inside, and the positive charge within the cell propels the outflow of potassium ions through delayed-rectifier voltage-gated potassium channels. Since the potassium channels within the cell membrane are delayed, any further entrance of sodium activates more and more voltage-gated sodium channels. Depolarization above threshold results in an increase in the conductance of Na sufficient for inward sodium movement to swamp outward potassium movement immediately. [3] If the influx of sodium ions fails to reach threshold, then sodium conductance does not increase a sufficient amount to override the resting potassium conductance. In that case, subthreshold membrane potential oscillations are observed in some type of neurons. If successful, the sudden influx of positive charge depolarizes the membrane, and potassium is delayed in re-establishing, or hyperpolarizing, the cell. Sodium influx depolarizes the cell in attempt to establish its own equilibrium potential (about +52 mV) to make the inside of the cell more positive relative to the outside.


The value of threshold can vary according to numerous factors. Changes in the ion conductances of sodium or potassium can lead to either a raised or lowered value of threshold. Additionally, the diameter of the axon, density of voltage activated sodium channels, and properties of sodium channels within the axon all affect the threshold value. [8] Typically in the axon or dendrite, there are small depolarizing or hyperpolarizing signals resulting from a prior stimulus. The passive spread of these signals depend on the passive electrical properties of the cell. The signals can only continue along the neuron to cause an action potential further down if they are strong enough to make it past the cell's membrane resistance and capacitance. For example, a neuron with a large diameter has more ionic channels in its membrane than a smaller cell, resulting in a lower resistance to the flow of ionic current. The current spreads quicker in a cell with less resistance, and is more likely to reach the threshold at other portions of the neuron. [3]

The threshold potential has also been shown experimentally to adapt to slow changes in input characteristics by regulating sodium channel density as well as inactivating these sodium channels overall. Hyperpolarization by the delayed-rectifier potassium channels causes a relative refractory period that makes it much more difficult to reach threshold. The delayed-rectifier potassium channels are responsible for the late outward phase of the action potential, where they open at a different voltage stimulus compared to the quickly activated sodium channels. They rectify, or repair, the balance of ions across the membrane by opening and letting potassium flow down its concentration gradient from inside to outside the cell. They close slowly as well, resulting in an outward flow of positive charge that exceeds the balance necessary. It results in excess negativity in the cell, requiring an extremely large stimulus and resulting depolarization to cause a response.

Tracking techniques

Threshold tracking techniques test nerve excitability, and depend on the properties of axonal membranes and sites of stimulation. They are extremely sensitive to the membrane potential and changes in this potential. These tests can measure and compare a control threshold (or resting threshold) to a threshold produced by a change in the environment, by a preceding single impulse, an impulse train, or a subthreshold current. [9] Measuring changes in threshold can indicate changes in membrane potential, axonal properties, and/or the integrity of the myelin sheath.

Threshold tracking allows for the strength of a test stimulus to be adjusted by a computer in order to activate a defined fraction of the maximal nerve or muscle potential. A threshold tracking experiment consists of a 1-ms stimulus being applied to a nerve in regular intervals. [10] The action potential is recorded downstream from the triggering impulse. The stimulus is automatically decreased in steps of a set percentage until the response falls below the target (generation of an action potential). Thereafter, the stimulus is stepped up or down depending on whether the previous response was lesser or greater than the target response until a resting (or control) threshold has been established. Nerve excitability can then be changed by altering the nerve environment or applying additional currents. Since the value of a single threshold current provides little valuable information because it varies within and between subjects, pairs of threshold measurements, comparing the control threshold to thresholds produced by refractoriness, supernormality, strength-duration time constant or "threshold electrotonus" are more useful in scientific and clinical study. [11]

Tracking threshold has advantages over other electrophysiological techniques, like the constant stimulus method. This technique can track threshold changes within a dynamic range of 200% and in general give more insight into axonal properties than other tests. [12] Also, this technique allows for changes in threshold to be given a quantitative value, which when mathematically converted into a percentage, can be used to compare single fiber and multifiber preparations, different neuronal sites, and nerve excitability in different species. [12]

"Threshold electrotonus"

A specific threshold tracking technique is threshold electrotonus, which uses the threshold tracking set-up to produce long-lasting subthreshold depolarizing or hyperpolarizing currents within a membrane. Changes in cell excitability can be observed and recorded by creating these long-lasting currents. Threshold decrease is evident during extensive depolarization, and threshold increase is evident with extensive hyperpolarization. With hyperpolarization, there is an increase in the resistance of the internodal membrane due to closure of potassium channels, and the resulting plot "fans out". Depolarization produces has the opposite effect, activating potassium channels, producing a plot that "fans in". [13]

The most important factor determining threshold electrotonus is membrane potential, so threshold electrotonus can also be used as an index of membrane potential. Furthermore, it can be used to identify characteristics of significant medical conditions through comparing the effects of those conditions on threshold potential with the effects viewed experimentally. For example, ischemia and depolarization cause the same "fanning in" effect of the electrotonus waveforms. This observation leads to the conclusion that ischemia may result from over-activation of potassium channels. [14]

Clinical significance

The role of the threshold potential has been implicated in a clinical context, namely in the functioning of the nervous system itself as well as in the cardiovascular system.

Febrile seizures

A febrile seizure, or "fever fit", is a convulsion associated with a significant rise in body temperature, occurring most commonly in early childhood. Repeated episodes of childhood febrile seizures are associated with an increased risk of temporal lobe epilepsy in adulthood. [15]

With patch clamp recording, an analogous state was replicated in vitro in rat cortical neurons after induction of febrile body temperatures; a notable decrease in threshold potential was observed. The mechanism for this decrease possibly involves suppression of inhibition mediated by the GABAB receptor with excessive heat exposure. [15]

ALS and diabetes

Abnormalities in neuronal excitability have been noted in amyotrophic lateral sclerosis and diabetes patients. While the mechanism ultimately responsible for the variance differs between the two conditions, tests through a response to ischemia indicate a similar resistance, ironically, to ischemia and resulting paresthesias. As ischemia occurs through inhibition of the sodium-potassium pump, abnormalities in the threshold potential are hence implicated. [12]


Since the 1940s, the concept of diastolic depolarization, or "pacemaker potential", has become established; this mechanism is a characteristic distinctive of cardiac tissue. [16] When the threshold is reached and the resulting action potential fires, a heartbeat results from the interactions; however, when this heartbeat occurs at an irregular time, a potentially serious condition known as arrythmia may result.

Use of medications

A variety of drugs can present prolongation of the QT interval as a side effect. Prolongation of this interval is a result of a delay in sodium and calcium channel inactivation; without proper channel inactivation, the threshold potential is reached prematurely and thus arrhythmia tends to result. [17] These drugs, known as pro-arrhythmic agents, include antimicrobials, antipsychotics, methadone, and, ironically, antiarrhythmic agents. [18] The use of such agents is particularly frequent in intensive care units, and special care must be exercised when QT intervals are prolonged in such patients: arrhythmias as a result of prolonged QT intervals include the potentially fatal torsades de pointes, or TdP. [17]

Role of diet

Diet may be a variable in the risk of arrhythmia. Polyunsaturated fatty acids, found in fish oils and several plant oils, [19] serve a role in the prevention of arrhythmias. [20] By inhibiting the voltage-dependent sodium current, these oils shift the threshold potential to a more positive value; therefore, an action potential requires increased depolarization. [20] Clinically therapeutic use of these extracts remains a subject of research, but a strong correlation is established between regular consumption of fish oil and lower frequency of hospitalization for atrial fibrillation, a severe and increasingly common arrythmia. [21]


  1. Seifter 2005, p. 55.
  2. Rushton 1927, p. 358.
  3. 1 2 3 Nicholls 2012, p. 121.
  4. Nicholls 2012, p. 122.
  5. Stuart 1997, p. 127.
  6. Trautwein 1963, p. 330.
  7. 1 2 Nicholls 2012, p. 144.
  8. Trautwein 1963, p. 281.
  9. Bostock 1997, p. 137.
  10. Bostock 1997, p. 138.
  11. Burke 2001, p. 1576.
  12. 1 2 3 Bostock 1997, p. 141.
  13. Burke 2001, p. 1581.
  14. Bostock 1997, p. 150.
  15. 1 2 Wang 2011, p. 87.
  16. Monfredi 2010, p. 1392.
  17. 1 2 Nelson 2011, p. 292.
  18. Nelson 2011, p. 291.
  19. "Polyunsaturated Fat". American Heart Association. Retrieved 22 May 2018.
  20. 1 2 Savelieva 2010, p. 213.
  21. Savelieva 2010, pp. 213–215.

Related Research Articles

Cardiac pacemaker

The contraction of cardiac muscle in all animals is initiated by electrical impulses known as action potentials. The rate at which these impulses fire controls the rate of cardiac contraction, that is, the heart rate. The cells that create these rhythmic impulses, setting the pace for blood pumping, are called pacemaker cells, and they directly control the heart rate. They make up the cardiac pacemaker, that is, the natural pacemaker of the heart. In most humans, the concentration of pacemaker cells in the sinoatrial (SA) node is the natural pacemaker, and the resultant rhythm is a sinus rhythm.

Refractory period (physiology) 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 to respond on stimuli, if the object stays in the specific refractory state. In common sense, refractory period is the characteristic recovery time, a period of time that is associated with the motion of the image point on the left branch of the isocline .

Hyperpolarization is a change in a cell's membrane potential that makes it more negative. It is the opposite of a depolarization. It inhibits action potentials by increasing the stimulus required to move the membrane potential to the action potential threshold.

Graded potential

Graded potentials are changes in membrane potential that vary in size, as opposed to being all-or-none. They include diverse potentials such as receptor potentials, electrotonic potentials, subthreshold membrane potential oscillations, slow-wave potential, pacemaker potentials, and synaptic potentials, which scale with the magnitude of the stimulus. They arise from the summation of the individual actions of ligand-gated ion channel proteins, and decrease over time and space. They do not typically involve voltage-gated sodium and potassium channels. These impulses are incremental and may be excitatory or inhibitory. They occur at the postsynaptic dendrite in response to presynaptic neuron firing and release of neurotransmitter, or may occur in skeletal, smooth, or cardiac muscle in response to nerve input. The magnitude of a graded potential is determined by the strength of the stimulus.

Axon hillock Portion of the neuronal cell soma from which the axon originates.

The axon hillock is a specialized part of the cell body of a neuron that connects to the axon. It can be identified using light microscopy from its appearance and location in a neuron and from its sparse distribution of Nissl substance.

The cardiac action potential is a brief change in voltage across the cell membrane of heart cells. This is caused by the movement of charged atoms between the inside and outside of the cell, through proteins called ion channels. The cardiac action potential differs from action potentials found in other types of electrically excitable cells, such as nerves. Action potentials also vary within the heart; this is due to the presence of different ion channels in different cells.

End-plate potential

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.

In neuroscience, repolarization refers to the change in membrane potential that returns it to a negative value just after the depolarization phase of an action potential has changed the membrane potential to a positive value. The repolarization phase usually returns the membrane potential back to the resting membrane potential. The efflux of K+ ions results in the falling phase of an action potential. The ions pass through the selectivity filter of the K+ channel pore.

Molecular neuroscience is a branch of neuroscience that observes concepts in molecular biology applied to the nervous systems of animals. The scope of this subject covers topics such as molecular neuroanatomy, mechanisms of molecular signaling in the nervous system, the effects of genetics and epigenetics on neuronal development, and the molecular basis for neuroplasticity and neurodegenerative diseases. As with molecular biology, molecular neuroscience is a relatively new field that is considerably dynamic.


Rheobase is a measure of membrane potential. 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. 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.

Low-threshold spikes (LTS) refer to membrane depolarizations by the T-type calcium channel. LTS occur at low, negative, membrane depolarizations. They often follow a membrane hyperpolarization, which can be the result of decreased excitability or increased inhibition. LTS result in the neuron reaching the threshold for an action potential. LTS is a large depolarization due to an increase in Ca2+ conductance, so LTS is mediated by calcium (Ca2+) conductance. The spike is typically crowned by a burst of two to seven action potentials, which is known as a low-threshold burst. LTS are voltage dependent and are inactivated if the cell's resting membrane potential is more depolarized than −60mV. LTS are deinactivated, or recover from inactivation, if the cell is hyperpolarized and can be activated by depolarizing inputs, such as excitatory postsynaptic potentials (EPSP). LTS were discovered by Rodolfo Llinás and coworkers in 1980s.

Dendritic spike

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 demostrated 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.

Summation (neurophysiology)

Summation, which includes both spatial 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.

Cellular neuroscience is a branch of neuroscience that concerned with the study of neurons at a cellular level. This includes morphology and physiological properties of single neurons. Several techniques such as intracellular recording, patch-clamp, and voltage-clamp technique, pharmacology, confocal imaging, molecular biology, two photon laser scanning microscopy and Ca2+ imaging have been used to study activity at the cellular level. Cellular neuroscience examines the various types of neurons, the functions of different neurons, the influence of neurons upon each other, and how neurons work together.

Nonsynaptic plasticity

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 (EPSPs) and inhibitory postsynaptic potentials (IPSPs). 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.