1.
Action potential
–
In physiology, an action potential is a short-lasting event in which the electrical membrane potential of a cell rapidly rises and falls, following a consistent trajectory. Action potentials occur in several types of cells, called excitable cells, which include neurons, muscle cells. In other types of cells, their function is to activate intracellular processes. In muscle cells, for example, a potential is the first step in the chain of events leading to contraction. In beta cells of the pancreas, they provoke release of insulin, action potentials in neurons are also known as nerve impulses or spikes, and the temporal sequence of action potentials generated by a neuron is called its spike train. A neuron that emits an action potential is often said to fire, action potentials are generated by special types of voltage-gated ion channels embedded in a cells plasma membrane. When the channels open they allow a flow of sodium ions, which changes the electrochemical gradient. This then causes more channels to open, producing an electric current across the cell membrane. The process proceeds explosively until all of the ion channels are open. The rapid influx of ions causes the polarity of the plasma membrane to reverse. As the sodium channels close, sodium ions can no longer enter the neuron, potassium channels are then activated, and there is an outward current of potassium ions, returning the electrochemical gradient to the resting state. After an action potential has occurred, there is a transient negative shift, in animal cells, there are two primary types of action potentials. One type is generated by voltage-gated sodium channels, the other by voltage-gated calcium channels, sodium-based action potentials usually last for under one millisecond, whereas calcium-based action potentials may last for 100 milliseconds or longer. In some types of neurons, slow calcium spikes provide the force for a long burst of rapidly emitted sodium spikes. In cardiac muscle cells, on the hand, an initial fast sodium spike provides a primer to provoke the rapid onset of a calcium spike. Nearly all cell membranes in animals, plants and fungi maintain a voltage difference between the exterior and interior of the cell, called the membrane potential. A typical voltage across a cell membrane is –70 mV. In most types of cells the membrane potential usually stays fairly constant, some types of cells, however, are electrically active in the sense that their voltages fluctuate over time
2.
Brain
–
The brain is an organ that serves as the center of the nervous system in all vertebrate and most invertebrate animals. The brain is located in the head, usually close to the organs for senses such as vision. The brain is the most complex organ in a vertebrates body, in a human, the cerebral cortex contains approximately 15–33 billion neurons, each connected by synapses to several thousand other neurons. Physiologically, the function of the brain is to exert centralized control over the other organs of the body, the brain acts on the rest of the body both by generating patterns of muscle activity and by driving the secretion of chemicals called hormones. This centralized control allows rapid and coordinated responses to changes in the environment, the operations of individual brain cells are now understood in considerable detail but the way they cooperate in ensembles of millions is yet to be solved. This article compares the properties of brains across the range of animal species. It deals with the human brain insofar as it shares the properties of other brains, the ways in which the human brain differs from other brains are covered in the human brain article. Several topics that might be covered here are instead covered there because more can be said about them in a human context. The most important is brain disease and the effects of brain damage, the shape and size of the brain varies greatly between species, and identifying common features is often difficult. Nevertheless, there are a number of principles of architecture that apply across a wide range of species. Some aspects of structure are common to almost the entire range of animal species, others distinguish advanced brains from more primitive ones. The simplest way to gain information about brain anatomy is by visual inspection, Brain tissue in its natural state is too soft to work with, but it can be hardened by immersion in alcohol or other fixatives, and then sliced apart for examination of the interior. Visually, the interior of the consists of areas of so-called grey matter, with a dark color, separated by areas of white matter. Further information can be gained by staining slices of tissue with a variety of chemicals that bring out areas where specific types of molecules are present in high concentrations. It is also possible to examine the microstructure of brain tissue using a microscope, the brains of all species are composed primarily of two broad classes of cells, neurons and glial cells. Glial cells come in types, and perform a number of critical functions, including structural support, metabolic support, insulation. Neurons, however, are considered the most important cells in the brain. The property that makes neurons unique is their ability to send signals to target cells over long distances
3.
Nobel Prize in Physiology or Medicine
–
The Nobel Prize in Physiology or Medicine, administered by the Nobel Foundation, is awarded once a year for outstanding discoveries in the fields of life sciences and medicine. It is one of five Nobel Prizes established in 1895 by Swedish chemist Alfred Nobel, Nobel was personally interested in experimental physiology and wanted to establish a prize for progress through scientific discoveries in laboratories. The Nobel Prize is presented to the recipient at a ceremony on 10 December, the anniversary of Nobels death, along with a diploma. The front side of the medal provides the profile of Alfred Nobel as depicted on the medals for Physics, Chemistry. As of 2015,106 Nobel Prizes in Physiology or Medicine have been awarded to 198 men and 12 women. The first Nobel Prize in Physiology or Medicine was awarded in 1901 to the German physiologist Emil von Behring, for his work on serum therapy and this includes one to António Egas Moniz in 1949 for the prefrontal leucotomy, bestowed despite protests from the medical establishment. Other controversies resulted from disagreements over who was included in the award, the 1952 prize to Selman Waksman was litigated in court, and half the patent rights awarded to his co-discoverer Albert Schatz who was not recognized by the prize. The 1962 prize awarded to James D, since the Nobel Prize rules forbid nominations of the deceased, longevity is an asset, one prize being awarded as long as 50 years after the discovery. Alfred Nobel was born on 21 October 1833 in Stockholm, Sweden into a family of engineers and he was a chemist, engineer and inventor who amassed a fortune during his lifetime, most of it from his 355 inventions of which dynamite is the most famous. He was interested in experimental physiology and set up his own labs in France, in 1888, Nobel was surprised to read his own obituary, titled The merchant of death is dead, in a French newspaper. Though Nobel wrote several wills during his lifetime, the last was written a little over a year before he died at the age of 63, because his will was contested, it was not approved by the Storting until 26 April 1897. After Nobels death, the Nobel Foundation was set up to manage the assets of the bequest, in 1900, the Nobel Foundations newly created statutes were promulgated by Swedish King Oscar II. According to Nobels will, the Karolinska Institutet in Sweden, a medical school, today, the prize is commonly referred to as the Nobel Prize in Medicine. It was important to Nobel that the prize be awarded for a discovery, per the provisions of the will, only select persons are eligible to nominate individuals for the award. Past Nobel laureates may also nominate, until 1977, all professors of Karolinska Institutet together decided on the Nobel Prize in Physiology or Medicine. Therefore, the Nobel Assembly was constituted, consisting of 50 professors at Karolinska Institutet. It elects the Nobel Committee with 5 members who evaluate the nominees, the Secretary who is in charge of the organization, in 1968, a provision was added that no more than three persons may share a Nobel prize. True to its mandate, the Committee has selected researchers working in the sciences over those who have made applied contributions
4.
Voltage
–
Voltage, electric potential difference, electric pressure or electric tension is the difference in electric potential energy between two points per unit electric charge. The voltage between two points is equal to the work done per unit of charge against an electric field to move the test charge between two points. This is measured in units of volts, voltage can be caused by static electric fields, by electric current through a magnetic field, by time-varying magnetic fields, or some combination of these three. A voltmeter can be used to measure the voltage between two points in a system, often a reference potential such as the ground of the system is used as one of the points. A voltage may represent either a source of energy or lost, used, given two points in space, x A and x B, voltage is the difference in electric potential between those two points. Electric potential must be distinguished from electric energy by noting that the potential is a per-unit-charge quantity. Like mechanical potential energy, the zero of electric potential can be chosen at any point, so the difference in potential, i. e. the voltage, is the quantity which is physically meaningful. The voltage between point A to point B is equal to the work which would have to be done, per unit charge, against or by the electric field to move the charge from A to B. The voltage between the two ends of a path is the energy required to move a small electric charge along that path. Mathematically this is expressed as the integral of the electric field. In the general case, both an electric field and a dynamic electromagnetic field must be included in determining the voltage between two points. Historically this quantity has also called tension and pressure. Pressure is now obsolete but tension is used, for example within the phrase high tension which is commonly used in thermionic valve based electronics. Voltage is defined so that negatively charged objects are pulled towards higher voltages, therefore, the conventional current in a wire or resistor always flows from higher voltage to lower voltage. Current can flow from lower voltage to higher voltage, but only when a source of energy is present to push it against the electric field. This is the case within any electric power source, for example, inside a battery, chemical reactions provide the energy needed for ion current to flow from the negative to the positive terminal. The electric field is not the only factor determining charge flow in a material, the electric potential of a material is not even a well defined quantity, since it varies on the subatomic scale. A more convenient definition of voltage can be found instead in the concept of Fermi level, in this case the voltage between two bodies is the thermodynamic work required to move a unit of charge between them
5.
Grid cell
–
A grid cell is a type of neuron in the brains of many species that allows them to understand their position in space. Grid cells were discovered in 2005 by Edvard Moser, May-Britt Moser and their students Torkel Hafting, Marianne Fyhn and they were awarded the 2014 Nobel Prize in Physiology or Medicine together with John OKeefe for their discoveries of cells that constitute a positioning system in the brain. The arrangement of spatial firing fields all at equal distances from their neighbors led to a hypothesis that these cells encode a representation of Euclidean space. The discovery also suggested a mechanism for dynamic computation of self-position based on updated information about position and direction. This regular triangle-pattern is what distinguishes grid cells from other types of cells that show spatial firing and this theory aroused a great deal of interest, and motivated hundreds of experimental studies aimed at clarifying the role of the hippocampus in spatial memory and spatial navigation. Because the entorhinal cortex provides by far the largest input to the hippocampus, the earliest studies, such as Quirk et al. described neurons in the entorhinal cortex as having relatively large and fuzzy place fields. The Mosers, however, thought it was possible that a different result would be obtained if recordings were made from a different part of the entorhinal cortex. The entorhinal cortex is a strip of tissue running along the edge of the rat brain from the ventral to the dorsal sides. This was relevant because several studies had shown that cells in the dorsal hippocampus have considerably sharper place fields than cells from more ventral levels. Every study of entorhinal spatial activity prior to 2004, however, had use of electrodes implanted near the ventral end of the EC. Accordingly, together with Marianne Fyhn, Sturla Molden and Menno Witter and they found that in the dorsal part of medial entorhinal cortex, cells had sharply defined place fields like in the hippocampus but the cells fired at multiple locations. The arrangement of the firing fields showed hints of regularity, the next set of experiments, reported in 2005, made use of a larger environment, which led to the recognition that the cells were actually firing in a hexagonal grid pattern. The study showed that cells at similar dorsal-to-ventral MEC levels had similar grid spacing and grid orientation, for their discovery of grid cells, May-Britt Moser, and Edvard Moser were awarded the Nobel Prize in Physiology or Medicine in 2014 alongside John OKeefe. Cells with this pattern have been found in all layers of the dorsocaudal medial entorhinal cortex. Layer II contains the largest density of pure grid cells, in the sense that they fire equally regardless of the direction in which an animal traverses a grid location, grid cells from deeper layers are intermingled with conjunctive cells and head direction cells. Grid cells that lie next to one another usually show the grid spacing and orientation. Cells recorded from separate electrodes at a distance from one another, however, cells that are located more ventrally generally have larger firing fields at each grid vertex, and correspondingly greater spacing between the grid vertices. These recordings only extended 3/4 of the way to the ventral tip, interestingly, such multi-scale representations have been shown to be information theoretically desirable
6.
Hippocampus proper
–
The hippocampus proper refers to the actual structure of the hippocampus which is made up of four regions or subfields. The subfields CA1, CA2, CA3, and CA4 use the initials of Cornu Ammonis, there are four regions in the hippocampus proper which form a neural circuit. CA1 is the first region in the circuit, from which a major output pathway goes to layer V of the entorhinal cortex. Another significant output is to the subiculum, CA2 is a small region located between CA1 and CA3. It receives some input from layer II of the cortex via the perforant path. Its pyramidal cells are more like those in CA3 than those in CA1 and it is often ignored due to its small size. CA3 receives input from the fibers of the granule cells in the dentate gyrus. The mossy fiber pathway ends in the stratum lucidum, the perforant path passes through the stratum lacunosum and ends in the stratum moleculare. There are also inputs from the septum and from the diagonal band of Broca which terminate in the stratum radiatum. The pyramidal cells in CA3 send some axons back to the dentate gyrus hilus, there are also a significant number of recurrent connections that terminate in CA3. Both the recurrent connections and the Schaffer collaterals terminate preferentially in the area in a dorsal direction from the originating cells. CA3 also sends a set of output fibers to the lateral septum. The region is divided into three divisions. CA3a is the part of the band that is most distant from the dentate. CA3b is the part of the band nearest to the fimbria. CA3c is nearest to the dentate, inserting into the hilus, CA3 overall, has been considered to be the “pacemaker” of the hippocampus. Much of the synchronous bursting activity associated with interictal epileptiform activity appears to be generated in CA3 and its excitatory collateral connectivity seems to be mostly responsible for this. CA3 uniquely, has pyramidal cell axon collaterals that ramify extensively with local regions, CA3 has been implicated in a number of working theories on memory and hippocampal learning processes
7.
Pyramidal cell
–
Pyramidal neurons are a type of neuron found in areas of the brain including the cerebral cortex, the hippocampus, and the amygdala. Pyramidal neurons are the primary units of the mammalian prefrontal cortex. Pyramidal neurons were first discovered and studied by Santiago Ramón y Cajal, since then, studies on pyramidal neurons have focused on topics ranging from neuroplasticity to cognition. One of the structural features of the pyramidal neuron is the conic shaped soma, or cell body. Other key structural features of the cell are a single axon, a large apical dendrite, multiple basal dendrites. The apical dendrites arise from the apex of the pyramidal cells soma, the apical dendrite is a single long thick dendrite that branches several times as distance from the soma increases and extends towards the cortical surface. The basal dendrites arise from the base of the pyramidal cells soma, the basal dendritic tree consists of three to five primary dendrites. As distance increases from the soma, the basal dendrites branch profusely, Pyramidal cells are among the largest neurons in the brain. Both in humans and rodents, pyramidal cell bodies average around 20 μm in length, Pyramidal dendrites typically range in diameter from half a micrometer to several micrometers. The length of a dendrite is usually several hundred micrometers. Due to branching, the total length of a pyramidal cell may reach several centimeters. The pyramidal cell’s axon is often longer and extensively branched. Dendritic spines receive most of the impulses that enter a pyramidal cell. Dendritic spines were first noted by Ramón y Cajal in 1888 by using Golgis method, Ramón y Cajal was also the first person to propose a physiological role of dendritic spines, increase the receptive surface area of the neuron. The greater the pyramidal cells surface area, the greater the ability to process. Dendritic spines are absent on the soma, and the number of spines increases away from it, the typical apical dendrite in a rat has at least 3000 dendritic spines. The average human apical dendrite is approximately twice the length of a rats, Pyramidal specification occurs during early development of the cerebrum. Progenitor cells are committed to the lineage in the subcortical proliferative ventricular zone
8.
Biological neural network
–
In neuroscience, a biological neural network is a series of interconnected neurons whose activation defines a recognizable linear pathway. The interface through which neurons interact with their neighbors usually consists of axon terminals connected via synapses to dendrites on other neurons. If the sum of the signals into one neuron surpasses a certain threshold. Biological neural networks have inspired the design of neural networks. The first rule of neuronal learning was described by Hebb in 1949, the neuroscientists Warren Sturgis McCulloch and Walter Pitts published the first works on the processing of neural networks. They showed theoretically that networks of neurons could implement logical, arithmetic. Simplified models of neurons were set up, now usually called perceptrons or artificial neurons. These simple models accounted for neural summation, later models also provided for excitatory and inhibitory synaptic transmission. The connections between neurons are more complex than those implemented in neural computing architectures. The basic kinds of connections between neurons are chemical synapses and electrical gap junctions, one principle by which neurons work is neural summation, i. e. potentials at the post synaptic membrane will sum up in the cell body. If the depolarization of the neuron at the axon goes above threshold an action potential will occur that travels down the axon to the endings to transmit a signal to other neurons. Excitatory and inhibitory synaptic transmission is realized mostly by inhibitory postsynaptic potentials, on the electrophysiological level, there are various phenomena which alter the response characteristics of individual synapses and individual neurons. These are often divided into short-term plasticity and long-term plasticity, long-term synaptic plasticity is often contended to be the most likely memory substrate. Usually the term neuroplasticity refers to changes in the brain that are caused by activity or experience, connections display temporal and spatial characteristics. Temporal characteristics refer to the continuously modified activity-dependent efficacy of synaptic transmission and it has been observed in several studies that the synaptic efficacy of this transmission can undergo short-term increase or decrease according to the activity of the presynaptic neuron. LTP is induced by a series of action potentials which cause a variety of biochemical responses, eventually, the reactions cause the expression of new receptors on the cellular membranes of the postsynaptic neurons or increase the efficacy of the existing receptors through phosphorylation. In some cells, however, neural backpropagation does occur through the dendritic arbor and may have important effects on synaptic plasticity, a neuron in the brain requires a single signal to a neuromuscular junction to stimulate contraction of the postsynaptic muscle cell. In the spinal cord, however, at least 75 afferent neurons are required to produce firing and this picture is further complicated by variation in time constant between neurons, as some cells can experience their EPSPs over a wider period of time than others
9.
Phase resetting in neurons
–
Phase resetting in neurons is a behavior observed in different biological oscillators and plays a role in creating neural synchronization as well as different processes within the body. Phase resetting in neurons is when the behavior of an oscillation is shifted. This occurs when a stimulus perturbs the phase within an oscillatory cycle and this activity pattern of neurons is a phenomenon seen in various neural circuits throughout the body and is seen in single neuron models and within clusters of neurons. Many of these models utilize phase response curves where the oscillation of a neuron is perturbed, burst of activity in patterns of behaviors occur through coupled oscillators using pulsatile signals, better known as pulse-coupled oscillators. The key to understanding this is in the patterns of neurons. Neural circuits are able to efficiently and effectively within milliseconds of experiencing a stimulus. The study of neuron synchrony could provide information on the differences occur in neural states such as normal. A phase response curve can be calculated by noting changes to its period over time depending on where in the cycle the input is applied, the perturbation left by the stimulus moves the stable cycle within the oscillation followed by a return to the stable cycle limit. The curve tracks the amount of advancement or delay due to the input in the oscillating neuron, the PRC assumes certain patterns of behavior in firing pattern as well as the network of oscillating neurons to model the oscillations. Currently, only a few circuits exist which can be modeling using a firing pattern. In order to model the behavior of firing neural circuits, the following is calculated to generate a PRC curve and its trajectory. To is defined as the period of an oscillator from the phase cycle defined as 0≤ ∅ ≤1. F = T0 If the perturbation to the cycle is infinitesimally small. This response function can be classified into different classes based upon its response, Type I Phase Response Curves are non-negative and strictly positive thus perturbations are only able to enhance a spike in phase, but never delay it. This occurs through a slight depolarization, such as postsynaptic potentials that increase the excitation of an axon, Type I PRCs are also shown to fire more slowly towards the onset of firing. Examples of Models that exhibit Type I PRCs in weakly coupled neural oscillators include the Connor, Type II Phase Response Curves can have negative and positive regions. Due to this characteristic, Type II PRCs are able to advance or delay changes in phase pending on the timing of perturbation that occurs and these curves can also have abrupt onset of firing and due to this, are unable to fire below their threshold. An example of a Type II PRC is seen within the Hodgkin–Huxley model, numerous research has suggested two primary assumptions that allow the use of PRCs to be used to predict the occurrence of synchrony within neural oscillation
10.
John O'Keefe (neuroscientist)
–
He is known for his discovery of place cells in the hippocampus and his discovery that they show a specific kind of temporal coding in the form of theta phase precession. In 2014, he received the Kavli Prize in Neuroscience for the discovery of specialized brain networks for memory and cognition, together with Brenda Milner and he shared the Nobel Prize in Physiology or Medicine in 2014 together with May-Britt Moser and Edvard Moser. Born in New York City to Irish immigrant parents, OKeefe attended Regis High School and received a BA degree from the City College of New York. He went on to study at McGill University in Montreal, where he obtained an MA degree in 1964, and he originally went to University College London in 1967 as a US NIMH postdoctoral fellow working with the late Patrick Wall. He has been ever since, and was awarded a professorship in 1987. He is a citizen of both the United States and the United Kingdom, o’Keefe and his student Jonathan Dostrovsky discovered place cells by systematically analyzing the environmental factors influencing the firing properties of individual hippocampal neurons. His many publications on place cells have been highly cited, in addition, he published an influential book with Lynn Nadel, proposing the functional role of the hippocampus as a cognitive map for spatial memory function. In extensions of his work, place cells have been analyzed experimentally or simulated in models in hundreds of papers, in a 1993 paper, he and Michael Recce demonstrated that place cells spike at different phases relative to theta rhythm oscillations in the local field potential of the hippocampus. This effect has been replicated in subsequent papers, providing evidence for the coding of sensory input by the timing of spikes. Numerous models have addressed the potential mechanisms of theta phase precession. In a paper in 1996, OKeefe and Neil Burgess presented data showing shifts in the position, in this and subsequent papers, they presented a model of this phenomenon predicting the existence of boundary vector cells that would respond at a specific distance from barriers in the environment. OKeefe was elected a Fellow of the Royal Society in 1992, in addition, he received the Feldberg Foundation Prize in 2001 and the Grawemeyer Award in psychology in 2006. Later in 2008, OKeefe was awarded the Gruber Prize in Neuroscience and he was appointed as the inaugural director of the Sainsbury Wellcome Centre for Neural Circuits and Behaviour. In 2013 he received the Louisa Gross Horwitz Prize, in 2014, he was a co-recipient of the Kavli Prize awarded by the Norwegian Academy of Science and Letters with Brenda Milner and Marcus Raichle. In 2016 he was elected to the National Academy of Sciences, further, he was awarded the Nobel Prize in Physiology or Medicine 2014, with May-Britt Moser and Edvard Moser. OKeefe received an honorary Doctor of Science degree from University College Cork on 15 December 2014. In May 2015, he received one from The City College of New York, on 10 March 2015 OKeefe was the guest on BBC Radio 4s The Life Scientific Official website at University College London
11.
Neural oscillation
–
Neural oscillation is rhythmic or repetitive neural activity in the central nervous system. Neural tissue can generate oscillatory activity in many ways, driven either by mechanisms within individual neurons or by interactions between neurons, at the level of neural ensembles, synchronized activity of large numbers of neurons can give rise to macroscopic oscillations, which can be observed in an electroencephalogram. Oscillatory activity in groups of neurons generally arises from feedback connections between the neurons that result in the synchronization of their firing patterns, the interaction between neurons can give rise to oscillations at a different frequency than the firing frequency of individual neurons. A well-known example of neural oscillations is alpha activity. Neural oscillations were observed by researchers as early as 1924, more than 50 years later, intrinsic oscillatory behavior was encountered in vertebrate neurons, but its functional role is still not fully understood. The possible roles of neural oscillations include feature binding, information transfer mechanisms, over the last decades more insight has been gained, especially with advances in brain imaging. A major area of research in neuroscience involves determining how oscillations are generated, oscillatory activity in the brain is widely observed at different levels of organization and is thought to play a key role in processing neural information. Numerous experimental studies support a role of neural oscillations, a unified interpretation. In general, oscillations can be characterized by their frequency, amplitude and these signal properties can be extracted from neural recordings using time-frequency analysis. In large-scale oscillations, amplitude changes are considered to result from changes in synchronization within a neural ensemble, in addition to local synchronization, oscillatory activity of distant neural structures can synchronize. Neural oscillations and synchronization have been linked to cognitive functions such as information transfer, perception, motor control. Neural oscillations have been most widely studied in neural activity generated by groups of neurons. Large-scale activity can be measured by such as EEG. In general, EEG signals have a broad spectral content similar to pink noise, the first discovered and best-known frequency band is alpha activity that can be detected from the occipital lobe during relaxed wakefulness and which increases when the eyes are closed. Other frequency bands are, delta, theta, beta and gamma frequency band, indeed, EEG signals change dramatically during sleep and show a transition from faster frequencies to increasingly slower frequencies such as alpha waves. In fact, different sleep stages are characterized by their spectral content. Consequently, neural oscillations have been linked to cognitive states, such as awareness and consciousness, although neural oscillations in human brain activity are mostly investigated using EEG recordings, they are also observed using more invasive recording techniques such as single-unit recordings. Neurons can generate patterns of action potentials or spikes
12.
Phase response curve
–
A phase response curve illustrates the transient change in the cycle period of an oscillation induced by a perturbation as a function of the phase at which it is received. PRCs are used in fields, examples of biological oscillations are the heartbeat, circadian rhythms. In humans and animals, there is a system that governs the phase relationship of an organisms internal circadian clock to a regular periodicity in the external environment. In most organisms, a stable phase relationship is desired, though in cases the desired phase will vary by season. In circadian rhythm research, a PRC illustrates the relationship between a time of administration and the magnitude of the treatments effect on circadian phase. Specifically, a PRC is a showing, by convention, time of the subjects endogenous day along the x-axis. The curve has one peak and one nadir in each 24-hour cycle, relative circadian time is plotted vs. phase shift magnitude. The treatment is usually specified as a set intensity and colour and duration of light exposure to the retina and skin, or a set dose. These curves are often consulted in the therapeutic setting, normally, the bodys various physiological rhythms will be synchronized within an individual organism, usually with respect to a master biological clock. Of particular importance is the sleep–wake cycle, various sleep disorders and externals stresses can interfere with this. People with non-24-hour sleep–wake disorder often experience an inability to maintain a consistent internal clock, extreme chronotypes usually maintain a consistent clock, but find that their natural clock does not align with the expectations of their social environment. PRC curves provide a point for therapeutic intervention. The two common used to shift the timing of sleep are light therapy, directed at the eyes. Either or both can be used daily, the phase adjustment is generally cumulative with consecutive daily administrations, and—at least partially—additive with concurrent administrations of distinct treatments. If the underlying disturbance is stable in nature, ongoing daily intervention is usually required, for jet lag, the intervention serves mainly to accelerate natural alignment, and ceases once desired alignment is achieved. The discussions below are restricted to the PRCs for the light, starting about two hours before an individuals regular bedtime, exposure of the eyes to light will delay the circadian phase, causing later wake-up time and later sleep onset. The delaying effect gets stronger as evening progresses, it is dependent on the wavelength. The effect is small in dim indoor lighting, about five hours after usual bedtime, coinciding with the body temperature nadir the PRC peaks and the effect changes abruptly from phase delay to phase advance
