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102-402: The Russian physiologist Ivan Pavlov studied classical conditioning with detailed experiments with dogs, and published the experimental results in 1897. In the study of digestion , Pavlov observed that the experimental dogs salivated when fed red meat. Pavlovian conditioning is distinct from operant conditioning (instrumental conditioning), through which the strength of a voluntary behavior

204-413: A CS than it does for a novel stimulus to become a CS, when the stimulus is paired with an effective US. This is one of the most common ways to measure the strength of learning in classical conditioning. A typical example of this procedure is as follows: a rat first learns to press a lever through operant conditioning . Then, in a series of trials, the rat is exposed to a CS, a light or a noise, followed by

306-553: A US through forward conditioning. Then a second neutral stimulus ("CS2") is paired with the first (CS1) and comes to yield its own conditioned response. For example: A bell might be paired with food until the bell elicits salivation. If a light is then paired with the bell, then the light may come to elicit salivation as well. The bell is the CS1 and the food is the US. The light becomes the CS2 once it

408-498: A US. A compound CS (CS1+CS2) is paired with a US. A separate test for each CS (CS1 and CS2) is performed. The blocking effect is observed in a lack of conditional response to CS2, suggesting that the first phase of training blocked the acquisition of the second CS. [REDACTED] Experiments on theoretical issues in conditioning have mostly been done on vertebrates , especially rats and pigeons. However, conditioning has also been studied in invertebrates , and very important data on

510-687: A behavioral sensitivity to acetophenone, which was accompanied by neuroanatomical and epigenetic changes that are believed to have been inherited from the parents' gametes . The learning involved in conditioned fear, as well as the underlying neurobiology, changes dramatically from infancy, across childhood and adolescence, into adulthood and aging. Specifically, infant animals show an inability to develop fear associations, whereas their adult counterparts develop fear memories much more readily. Previous research has indicated that adolescents show hampered fear extinction learning compared to children and adults. This finding may have clinical implications, as one of

612-653: A bell and visual stimuli. In the 19th century, physiological knowledge began to accumulate at a rapid rate, in particular with the 1838 appearance of the Cell theory of Matthias Schleiden and Theodor Schwann . It radically stated that organisms are made up of units called cells. Claude Bernard 's (1813–1878) further discoveries ultimately led to his concept of milieu interieur (internal environment), which would later be taken up and championed as " homeostasis " by American physiologist Walter B. Cannon in 1929. By homeostasis, Cannon meant "the maintenance of steady states in

714-463: A clear summary of this change in thinking, and its implications, in his 1988 article "Pavlovian conditioning: It's not what you think it is". Despite its widespread acceptance, Rescorla's thesis may not be defensible. Classical conditioning differs from operant or instrumental conditioning : in classical conditioning, behaviors are modified through the association of stimuli as described above, whereas in operant conditioning behaviors are modified by

816-503: A distinct subdiscipline. In 1920, August Krogh won the Nobel Prize for discovering how, in capillaries, blood flow is regulated. In 1954, Andrew Huxley and Hugh Huxley, alongside their research team, discovered the sliding filaments in skeletal muscle , known today as the sliding filament theory. Recently, there have been intense debates about the vitality of physiology as a discipline (Is it dead or alive?). If physiology

918-463: A dog's saliva produced as a CR differed in composition from that produced as a UR. The CR is sometimes even the opposite of the UR. For example: the unconditional response to electric shock is an increase in heart rate, whereas a CS that has been paired with the electric shock elicits a decrease in heart rate. (However, it has been proposed that only when the UR does not involve the central nervous system are

1020-459: A medical field originates in classical Greece , at the time of Hippocrates (late 5th century BC). Outside of Western tradition, early forms of physiology or anatomy can be reconstructed as having been present at around the same time in China , India and elsewhere. Hippocrates incorporated the theory of humorism , which consisted of four basic substances: earth, water, air and fire. Each substance

1122-499: A negative associate strength) then R-W predicts that the CS will not undergo extinction (its V will not decrease in size). The most important and novel contribution of the R–W model is its assumption that the conditioning of a CS depends not just on that CS alone, and its relationship to the US, but also on all other stimuli present in the conditioning situation. In particular, the model states that

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1224-465: A newly identified brain circuit is involved. Initially, the pre-limbic prefrontal cortex (PL) and the basolateral amygdala (BLA) were identified in memory recall. A week later, the central amygdala (CeA) and the paraventricular nucleus of the thalamus (PVT) were identified in memory recall, which are responsible for maintaining fear memories. This study shows how there are shifting circuits between short term recall and long term recall of fear memories. There

1326-473: A number of observations differentiate them, especially the contingencies whereby learning occurs. Together with operant conditioning , classical conditioning became the foundation of behaviorism , a school of psychology which was dominant in the mid-20th century and is still an important influence on the practice of psychological therapy and the study of animal behavior. Classical conditioning has been applied in other areas as well. For example, it may affect

1428-489: A person's eye could be followed by the sound of a buzzer. In temporal conditioning, a US is presented at regular intervals, for instance every 10 minutes. Conditioning is said to have occurred when the CR tends to occur shortly before each US. This suggests that animals have a biological clock that can serve as a CS. This method has also been used to study timing ability in animals (see Animal cognition ). The example below shows

1530-404: A piece of cardboard. A key idea behind the R–W model is that a CS signals or predicts the US. One might say that before conditioning, the subject is surprised by the US. However, after conditioning, the subject is no longer surprised, because the CS predicts the coming of the US. (The model can be described mathematically and that words like predict, surprise, and expect are only used to help explain

1632-417: A replica of the unconditioned response, but Pavlov noted that saliva produced by the CS differs in composition from that produced by the US. In fact, the CR may be any new response to the previously neutral CS that can be clearly linked to experience with the conditional relationship of CS and US. It was also thought that repeated pairings are necessary for conditioning to emerge, but many CRs can be learned with

1734-425: A single trial, especially in fear conditioning and taste aversion learning. Learning is fastest in forward conditioning. During forward conditioning, the onset of the CS precedes the onset of the US in order to signal that the US will follow. Two common forms of forward conditioning are delay and trace conditioning. [REDACTED] During simultaneous conditioning, the CS and US are presented and terminated at

1836-408: A source of the dynamic changes in subsequent neuronal gene expression in response to fear conditioning. Fear conditioning is thought to depend upon an area of the brain called the amygdala . The amygdala is involved in acquisition, storage, and expression of conditioned fear memory. Lesion studies have revealed that lesions drilled into the amygdala before fear conditioning prevent the acquisition of

1938-430: A unified science of life based on the cell actions, later renamed in the 20th century as cell biology . In the 20th century, biologists became interested in how organisms other than human beings function, eventually spawning the fields of comparative physiology and ecophysiology . Major figures in these fields include Knut Schmidt-Nielsen and George Bartholomew . Most recently, evolutionary physiology has become

2040-444: A weak stimulus is presented. During acquisition, the CS and US are paired as described above. The extent of conditioning may be tracked by test trials. In these test trials, the CS is presented alone and the CR is measured. A single CS-US pairing may suffice to yield a CR on a test, but usually a number of pairings are necessary and there is a gradual increase in the conditioned response to the CS. This repeated number of trials increase

2142-503: Is a behavioral paradigm in which organisms learn to predict aversive events. It is a form of learning in which an aversive stimulus (e.g. an electrical shock) is associated with a particular neutral context (e.g., a room) or neutral stimulus (e.g., a tone), resulting in the expression of fear responses to the originally neutral stimulus or context. This can be done by pairing the neutral stimulus with an aversive stimulus (e.g., an electric shock, loud noise, or unpleasant odor ). Eventually,

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2244-550: Is a subdiscipline of botany concerned with the functioning of plants. Closely related fields include plant morphology , plant ecology , phytochemistry , cell biology , genetics , biophysics , and molecular biology . Fundamental processes of plant physiology include photosynthesis , respiration , plant nutrition , tropisms , nastic movements , photoperiodism , photomorphogenesis , circadian rhythms , seed germination , dormancy , and stomata function and transpiration . Absorption of water by roots, production of food in

2346-427: Is achieved through communication that occurs in a variety of ways, both electrical and chemical. Changes in physiology can impact the mental functions of individuals. Examples of this would be the effects of certain medications or toxic levels of substances. Change in behavior as a result of these substances is often used to assess the health of individuals. Much of the foundation of knowledge in human physiology

2448-467: Is also seen in the hippocampus at one hour and 24 hours after fear conditioning. These changes are transient in the hippocampal neurons, and almost none are present in the hippocampus after four weeks. By 4 weeks after the event, the memory of the fear conditioning event is more permanently stored in the anterior cingulate cortex. As shown in the rodent brain, neuronal gene expression is dynamically changed in response to fear conditioning. In particular,

2550-456: Is another immediate early gene whose expression in neurons can be induced by sustained synaptic activity. DNMTs bind to DNA and methylate cytosines at particular locations in the genome. If this methylation is prevented by DNMT inhibitors, then memories do not form. If DNMT3A2 is over-expressed in the hippocampus of young adult mice it converts a weak learning experience into long-term memory and also enhances fear memory formation. Neurons in

2652-400: Is essential for diagnosing and treating health conditions and promoting overall wellbeing. It seeks to understand the mechanisms that work to keep the human body alive and functioning, through scientific enquiry into the nature of mechanical, physical, and biochemical functions of humans, their organs, and the cells of which they are composed. The principal level of focus of physiology is at

2754-469: Is known for having a corresponding humor: black bile, phlegm, blood, and yellow bile, respectively. Hippocrates also noted some emotional connections to the four humors, on which Galen would later expand. The critical thinking of Aristotle and his emphasis on the relationship between structure and function marked the beginning of physiology in Ancient Greece . Like Hippocrates , Aristotle took to

2856-476: Is modified, either by reinforcement or by punishment . However, classical conditioning can affect operant conditioning; classically conditioned stimuli can reinforce operant responses. Classical conditioning is a basic behavioral mechanism, and its neural substrates are now beginning to be understood. Though it is sometimes hard to distinguish classical conditioning from other forms of associative learning (e.g. instrumental learning and human associative memory ),

2958-418: Is no change in behavior or response, only change in where the memory was recalled from. In addition to the amygdala, the hippocampus and the anterior cingulate cortex are important in fear conditioning. Fear conditioning in the rat is stored at early times in the hippocampus, with alterations in hippocampal gene expression observed at 1 hour and 24 hours after the event. In the mouse, changed gene expression

3060-518: Is not exclusively the fear center, but also an area for responding to various environmental stimuli. Several studies have shown that when faced with unpredictable neutral stimuli, amygdala activity increases. Therefore, even in situations of uncertainty and not necessarily fear, the amygdala plays a role in alerting other brain regions that encourage safety and survival responses. In the mid-1950s Lawrence Weiskrantz demonstrated that monkeys with lesions of amygdala failed to avoid an aversive shock while

3162-464: Is often measured with freezing (a period of watchful immobility) or fear potentiated startle (the augmentation of the startle reflex by a fearful stimulus). Changes in heart rate , breathing , and muscle responses via electromyography can also be used to measure conditioned fear. A number of theorists have argued that conditioned fear coincides substantially with the mechanisms, both functional and neural, of clinical anxiety disorders. Research into

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3264-499: Is paired with a US until asymptotic CR levels are reached. CS+/US trials are continued, but these are interspersed with trials on which the CS+ is paired with a second CS, (the CS-) but not with the US (i.e. CS+/CS- trials). Typically, organisms show CRs on CS+/US trials, but stop responding on CS+/CS− trials. This form of classical conditioning involves two phases. A CS (CS1) is paired with

3366-424: Is paired with the CS1. [REDACTED] Backward conditioning occurs when a CS immediately follows a US. Unlike the usual conditioning procedure, in which the CS precedes the US, the conditioned response given to the CS tends to be inhibitory. This presumably happens because the CS serves as a signal that the US has ended, rather than as a signal that the US is about to appear. For example, a puff of air directed at

3468-580: Is perhaps less visible nowadays than during the golden age of the 19th century, it is in large part because the field has given birth to some of the most active domains of today's biological sciences, such as neuroscience , endocrinology , and immunology . Furthermore, physiology is still often seen as an integrative discipline, which can put together into a coherent framework data coming from various different domains. Initially, women were largely excluded from official involvement in any physiological society. The American Physiological Society , for example,

3570-649: Is the scientific study of functions and mechanisms in a living system . As a subdiscipline of biology , physiology focuses on how organisms , organ systems , individual organs , cells , and biomolecules carry out chemical and physical functions in a living system. According to the classes of organisms , the field can be divided into medical physiology , animal physiology , plant physiology , cell physiology , and comparative physiology . Central to physiological functioning are biophysical and biochemical processes, homeostatic control mechanisms, and communication between cells. Physiological state

3672-555: Is the condition of normal function. In contrast, pathological state refers to abnormal conditions , including human diseases . The Nobel Prize in Physiology or Medicine is awarded by the Royal Swedish Academy of Sciences for exceptional scientific achievements in physiology related to the field of medicine . Because physiology focuses on the functions and mechanisms of living organisms at all levels, from

3774-399: Is the response to the conditioned stimulus, whereas the unconditioned response (UR) corresponds to the unconditioned stimulus. Pavlov reported many basic facts about conditioning; for example, he found that learning occurred most rapidly when the interval between the CS and the appearance of the US was relatively short. As noted earlier, it is often thought that the conditioned response is

3876-418: The CR and the UR opposites.) The Rescorla–Wagner (R–W) model is a relatively simple yet powerful model of conditioning. The model predicts a number of important phenomena, but it also fails in important ways, thus leading to a number of modifications and alternative models. However, because much of the theoretical research on conditioning in the past 40 years has been instigated by this model or reactions to it,

3978-422: The CR is said to be "extinguished." [REDACTED] External inhibition may be observed if a strong or unfamiliar stimulus is presented just before, or at the same time as, the CS. This causes a reduction in the conditioned response to the CS. Several procedures lead to the recovery of a CR that had been first conditioned and then extinguished. This illustrates that the extinction procedure does not eliminate

4080-459: The CS. As a result of this "surprising" outcome, the associative strength of the CS takes a step down. Extinction is complete when the strength of the CS reaches zero; no US is predicted, and no US occurs. However, if that same CS is presented without the US but accompanied by a well-established conditioned inhibitor (CI), that is, a stimulus that predicts the absence of a US (in R-W terms, a stimulus with

4182-416: The CS. In the equation, V represents the current associative strength of the CS, and ∆V is the change in this strength that happens on a given trial. ΣV is the sum of the strengths of all stimuli present in the situation. λ is the maximum associative strength that a given US will support; its value is usually set to 1 on trials when the US is present, and 0 when the US is absent. α and β are constants related to

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4284-523: The EGR1 proteins bring TET1 proteins to hundreds of genes, allowing TET1 to initiate DNA demethylation of those genes. DNMT3A2 protein is a de novo DNA methyltransferase , adding methylation to cytosines in DNA. Expression of DNMT3A2 proteins in hippocampus neurons in culture preferentially targeted the addition of new methylation to more than 200 genes involved in synaptic plasticity. Expressions of IEGs are

4386-468: The Rescorla-Wagner equation. It specifies the amount of learning that will occur on a single pairing of a conditioning stimulus (CS) with an unconditioned stimulus (US). The above equation is solved repeatedly to predict the course of learning over many such trials. In this model, the degree of learning is measured by how well the CS predicts the US, which is given by the "associative strength" of

4488-413: The R–W model deserves a brief description here. The Rescorla-Wagner model argues that there is a limit to the amount of conditioning that can occur in the pairing of two stimuli. One determinant of this limit is the nature of the US. For example: pairing a bell with a juicy steak is more likely to produce salivation than pairing the bell with a piece of dry bread, and dry bread is likely to work better than

4590-432: The UR, the CR is acquired through experience, and it is also less permanent than the UR. Usually the conditioned response is similar to the unconditioned response, but sometimes it is quite different. For this and other reasons, most learning theorists suggest that the conditioned stimulus comes to signal or predict the unconditioned stimulus, and go on to analyse the consequences of this signal. Robert A. Rescorla provided

4692-402: The US causes a gradual increase in the associative strength of the CS. This increase is determined by the nature of the US (e.g. its intensity). The amount of learning that happens during any single CS-US pairing depends on the difference between the total associative strengths of CS and other stimuli present in the situation (ΣV in the equation), and a maximum set by the US (λ in the equation). On

4794-402: The US is fully predicted, the associative strength of the CS stops growing, and conditioning is complete. The associative process described by the R–W model also accounts for extinction (see "procedures" above). The extinction procedure starts with a positive associative strength of the CS, which means that the CS predicts that the US will occur. On an extinction trial the US fails to occur after

4896-409: The US is predicted by the sum of the associative strengths of all stimuli present in the conditioning situation. Learning is controlled by the difference between this total associative strength and the strength supported by the US. When this sum of strengths reaches a maximum set by the US, conditioning ends as just described. The R–W explanation of the blocking phenomenon illustrates one consequence of

4998-516: The US, a mild electric shock. An association between the CS and US develops, and the rat slows or stops its lever pressing when the CS comes on. The rate of pressing during the CS measures the strength of classical conditioning; that is, the slower the rat presses, the stronger the association of the CS and the US. (Slow pressing indicates a "fear" conditioned response, and it is an example of a conditioned emotional response; see section below.) Typically, three phases of conditioning are used. A CS (CS+)

5100-417: The US, but the US also occurs at other times. If this occurs, it is predicted that the US is likely to happen in the absence of the CS. In other words, the CS does not "predict" the US. In this case, conditioning fails and the CS does not come to elicit a CR. This finding – that prediction rather than CS-US pairing is the key to conditioning – greatly influenced subsequent conditioning research and theory. In

5202-404: The acquisition of any new behavior, but rather the tendency to respond in old ways to new stimuli. Thus, he theorized that the CS merely substitutes for the US in evoking the reflex response. This explanation is called the stimulus-substitution theory of conditioning. A critical problem with the stimulus-substitution theory is that the CR and UR are not always the same. Pavlov himself observed that

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5304-449: The acquisition, consolidation and extinction of conditioned fear promises to inform new drug based and psychotherapeutic treatments for an array of pathological conditions such as dissociation , phobias and post-traumatic stress disorder . Scientists have discovered that there is a set of brain connections that determine how fear memories are stored and recalled. While studying rats' ability to recall fear memories, researchers found

5406-447: The activation of downstream genes (see Regulation of gene expression#Regulation of transcription in learning and memory . EGR1 brings TET1 to promoter sites of genes that need to be demethylated and activated (transcribed) during memory formation. EGR-1, together with TET1, is employed in programming the distribution of DNA demethylation sites on brain DNA during memory formation and in long-term neuronal plasticity . DNMT3A2

5508-402: The amygdala as chiefly responsible for fear learning and memory. Additionally, inhibition of neurons in the amygdala disrupts fear acquisition, while stimulation of those neurons can drive fear-related behaviors, such as freezing behavior in rodents. This indicates that proper function of the amygdala is both necessary for fear conditioning and sufficient to drive fear behaviors. The amygdala

5610-514: The amygdala undergoes long-term potentiation during fear conditioning, and that ablation of amygdala cells disrupts both learning and expression of fear. Some types of fear conditioning (e.g. contextual and trace) also involve the hippocampus , an area of the brain believed to receive affective impulses from the amygdala and to integrate those impulses with previously existing information to make it meaningful. Some theoretical accounts of traumatic experiences suggest that amygdala-based fear bypasses

5712-404: The animals' digestive fluids outside the body, where they could be measured. Pavlov noticed that his dogs began to salivate in the presence of the technician who normally fed them, rather than simply salivating in the presence of food. Pavlov called the dogs' anticipatory salivation "psychic secretion". Putting these informal observations to an experimental test, Pavlov presented a stimulus (e.g.

5814-452: The associative nature of fear conditioning is reflected in the role of NMDARs as coincident detectors, where NMDAR activation requires simultaneous depolarization by US inputs combined with concurrent CS activation. Conditioned fear may be inherited transgenerationally. In one experiment, mice were conditioned to fear an acetophenone odor and then set up to breed subsequent generations of mice. Those subsequent generations of mice also showed

5916-423: The assumption just stated. In blocking (see "phenomena" above), CS1 is paired with a US until conditioning is complete. Then on additional conditioning trials a second stimulus (CS2) appears together with CS1, and both are followed by the US. Finally CS2 is tested and shown to produce no response because learning about CS2 was "blocked" by the initial learning about CS1. The R–W model explains this by saying that after

6018-431: The basolateral amygdala are responsible for the formation of conditioned fear memory. These neurons project to neurons in the central amygdala for the expression of a conditioned fear response. Damage to these areas in the amygdala would result in disruption of the expression of conditioned fear responses. Lesions in the basolateral amygdala have shown severe deficits in the expression of conditioned fear responses. Lesions in

6120-418: The blood . Santorio Santorio in 1610s was the first to use a device to measure the pulse rate (the pulsilogium ), and a thermoscope to measure temperature. In 1791 Luigi Galvani described the role of electricity in the nerves of dissected frogs. In 1811, César Julien Jean Legallois studied respiration in animal dissection and lesions and found the center of respiration in the medulla oblongata . In

6222-421: The body and the physiological processes through which they are regulated." In other words, the body's ability to regulate its internal environment. William Beaumont was the first American to utilize the practical application of physiology. Nineteenth-century physiologists such as Michael Foster , Max Verworn , and Alfred Binet , based on Haeckel 's ideas, elaborated what came to be called "general physiology",

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6324-399: The body's response to psychoactive drugs , the regulation of hunger, research on the neural basis of learning and memory, and in certain social phenomena such as the false consensus effect . Classical conditioning occurs when a conditioned stimulus (CS) is paired with an unconditioned stimulus (US). Usually, the conditioned stimulus is a neutral stimulus (e.g., the sound of a tuning fork ),

6426-401: The central amygdala have shown mild deficits in the expression of conditioned fear responses. One of the major neurotransmitters involved in conditioned fear learning is glutamate . It has been suggested that NMDA receptors (NMDARs) in the amygdala are necessary for fear memory acquisition, because disruption of NMDAR function disrupts development of fear responses in rodents. In addition,

6528-410: The conditioned response of fear, and lesions drilled in the amygdala after conditioning cause conditioned responses to be forgotten. Electrophysiological recordings from the amygdala have demonstrated that cells in that region undergo long-term potentiation (LTP), a form of synaptic plasticity believed to underlie learning. Pharmacological studies, synaptic studies, and human studies also implicate

6630-542: The death rate from surgery by a substantial amount. The Physiological Society was founded in London in 1876 as a dining club. The American Physiological Society (APS) is a nonprofit organization that was founded in 1887. The Society is, "devoted to fostering education, scientific research, and dissemination of information in the physiological sciences." In 1891, Ivan Pavlov performed research on "conditional responses" that involved dogs' saliva production in response to

6732-434: The developmental change in fear extinction learning. A history of stressors preceding a traumatic event increases the effect of fear conditioning in rodents. This phenomenon, named Stress-Enhanced Fear Learning (SEFL), has been demonstrated in both young (e.g. Poulos et al. 2014 ) and adult (e.g. Rau et al. 2009 ) rodents. Biological mechanisms underpinning SEFL have not yet been made clear, though it has been associated with

6834-411: The effect of conditioning. These procedures are the following: Stimulus generalization is said to occur if, after a particular CS has come to elicit a CR, a similar test stimulus is found to elicit the same CR. Usually the more similar the test stimulus is to the CS the stronger the CR will be to the test stimulus. Conversely, the more the test stimulus differs from the CS, the weaker the CR will be, or

6936-477: The effect they produce (i.e., reward or punishment). The best-known and most thorough early work on classical conditioning was done by Ivan Pavlov , although Edwin Twitmyer published some related findings a year earlier. During his research on the physiology of digestion in dogs, Pavlov developed a procedure that enabled him to study the digestive processes of animals over long periods of time. He redirected

7038-456: The election of women was celebrated in 2015 with the publication of the book "Women Physiologists: Centenary Celebrations And Beyond For The Physiological Society." ( ISBN   978-0-9933410-0-7 ) Prominent women physiologists include: Human physiology Animal physiology Plant physiology Fungal physiology Protistan physiology Algal physiology Bacterial physiology Fear conditioning Pavlovian fear conditioning

7140-480: The event, 9.17% of the genes in the genomes of rat hippocampus neurons are differentially methylated. The pattern of induced and repressed genes within hippocampal neurons appears to provide a molecular basis for forming the early transient memory of contextual fear conditioning in the hippocampus. When similar contextual fear conditioning was applied to a mouse, one hour after contextual fear conditioning there were 675 demethylated genes and 613 hypermethylated genes in

7242-1006: The expressions of immediate early genes (IEGs) such as Egr1 , c-Fos , and Arc are rapidly and selectively up-regulated in subsets of neurons in specific brain regions associated with learning and memory formation. A review in 2022 describes multiple steps in up-regulating the IEGs in neurons in the hippocampus during fear conditioning. IEGs are similarly up-regulated in the amygdala during fear conditioning. The multiple steps in up-regulating IEGs include activation of transcription factors , formation of chromatin loops , interaction of enhancers with promoters in chromatin loops and topoisomerase II beta-initiated temporary DNA double-strand breaks. At least two IEGs up-regulated by fear conditioning, Egr1 and Dnmt 3A2 (shown to be an IEG by Oliveira et al. ) affect DNA methylation , and thus expression, of many genes. Up-regulated EGR1 proteins associate with pre-existing nuclear TET1 proteins, and

7344-580: The extinction procedure, the CS is presented repeatedly in the absence of a US. This is done after a CS has been conditioned by one of the methods above. When this is done, the CR frequency eventually returns to pre-training levels. However, extinction does not eliminate the effects of the prior conditioning. This is demonstrated by spontaneous recovery – when there is a sudden appearance of the (CR) after extinction occurs – and other related phenomena (see "Recovery from extinction" below). These phenomena can be explained by postulating accumulation of inhibition when

7446-426: The first pairing of the CS and US, this difference is large and the associative strength of the CS takes a big step up. As CS-US pairings accumulate, the US becomes more predictable, and the increase in associative strength on each trial becomes smaller and smaller. Finally, the difference between the associative strength of the CS (plus any that may accrue to other stimuli) and the maximum strength reaches zero. That is,

7548-472: The food because its effects did not depend on previous experience. The metronome's sound is originally a neutral stimulus (NS) because it does not elicit salivation in the dogs. After conditioning, the metronome's sound becomes the conditioned stimulus (CS) or conditional stimulus; because its effects depend on its association with food. Likewise, the responses of the dog follow the same conditioned-versus-unconditioned arrangement. The conditioned response (CR)

7650-469: The genes to be transcribed and then translated into active proteins. One immediate early gene newly transcribed after a double-strand break is EGR1 . EGR1 is an important transcription factor in memory formation. It has an essential role in brain neuron epigenetic reprogramming. EGR1 recruits the TET1 protein that initiates a pathway of DNA demethylation . Removing DNA methylation marks allows

7752-549: The hippocampus and in the medial prefrontal cortex (mPFC), in two peaks, at 10 minutes and at 30 minutes after contextual fear conditioning. This appears to be earlier than the DNA methylations and demethylations of neuron DNA in the hippocampus that were measured at one hour and 24 hours after contextual fear conditioning (described above in the section Hippocampus ). The double strand breaks occur at known memory-related immediate early genes (among other genes) in neurons after neuron activation. These double-strand breaks allow

7854-648: The hippocampus during intense stress and can be stored somatically or as images that can return as physical symptoms or flashbacks without cognitive meaning. The hippocampus is one of the brain regions that undergoes major alterations in gene expression after contextual fear conditioning. Contextual fear conditioning applied to a rat causes about 500 genes to be up-regulated (possibly due to DNA demethylation of CpG sites ) and about 1,000 genes to be down-regulated (observed to be correlated with DNA methylation at CpG sites in promoter regions) (see Regulation of transcription in learning and memory ). By 24 hours after

7956-524: The hippocampus region of the mouse brain. These changes were transient in the hippocampal neurons, and almost none of these DNA methylation alterations were present in the hippocampus after four weeks. However, in mice subjected to contextual fear conditioning, after four weeks there were more than 1,000 differentially methylated genes and more than 1,000 differentially expressed genes in the mouse anterior cingulate cortex where long-term memories are stored. More than 100 DNA double-strand breaks occur, both in

8058-502: The humoral theory of disease, which also consisted of four primary qualities in life: hot, cold, wet and dry. Galen ( c.  130 –200 AD) was the first to use experiments to probe the functions of the body. Unlike Hippocrates, Galen argued that humoral imbalances can be located in specific organs, including the entire body. His modification of this theory better equipped doctors to make more precise diagnoses. Galen also played off of Hippocrates' idea that emotions were also tied to

8160-458: The humors, and added the notion of temperaments: sanguine corresponds with blood; phlegmatic is tied to phlegm; yellow bile is connected to choleric; and black bile corresponds with melancholy. Galen also saw the human body consisting of three connected systems: the brain and nerves, which are responsible for thoughts and sensations; the heart and arteries, which give life; and the liver and veins, which can be attributed to nutrition and growth. Galen

8262-410: The individual." In more differentiated organisms, the functional labor could be apportioned between different instruments or systems (called by him as appareils ). In 1858, Joseph Lister studied the cause of blood coagulation and inflammation that resulted after previous injuries and surgical wounds. He later discovered and implemented antiseptics in the operating room, and as a result, decreased

8364-447: The initial conditioning, CS1 fully predicts the US. Since there is no difference between what is predicted and what happens, no new learning happens on the additional trials with CS1+CS2, hence CS2 later yields no response. Physiology Physiology ( / ˌ f ɪ z i ˈ ɒ l ə dʒ i / ; from Ancient Greek φύσις ( phúsis )  'nature, origin' and -λογία ( -logía )  'study of')

8466-402: The leaves, and growth of shoots towards light are examples of plant physiology. Human physiology is the study of how the human body's systems and functions work together to maintain a stable internal environment. It includes the study of the nervous, endocrine, cardiovascular, respiratory, digestive, and urinary systems, as well as cellular and exercise physiology. Understanding human physiology

8568-449: The level of organs and systems within systems. The endocrine and nervous systems play major roles in the reception and transmission of signals that integrate function in animals. Homeostasis is a major aspect with regard to such interactions within plants as well as animals. The biological basis of the study of physiology, integration refers to the overlap of many functions of the systems of the human body, as well as its accompanied form. It

8670-400: The model.) Here the workings of the model are illustrated with brief accounts of acquisition, extinction, and blocking. The model also predicts a number of other phenomena, see main article on the model. Δ V = α β ( λ − Σ V ) {\displaystyle \Delta V=\alpha \beta (\lambda -\Sigma V)} This is

8772-455: The molecular and cellular level to the level of whole organisms and populations, its foundations span a range of key disciplines: There are many ways to categorize the subdisciplines of physiology: Although there are differences between animal , plant , and microbial cells, the basic physiological functions of cells can be divided into the processes of cell division , cell signaling , cell growth , and cell metabolism . Plant physiology

8874-416: The more it will differ from that previously observed. One observes stimulus discrimination when one stimulus ("CS1") elicits one CR and another stimulus ("CS2") elicits either another CR or no CR at all. This can be brought about by, for example, pairing CS1 with an effective US and presenting CS2 with no US. Latent inhibition refers to the observation that it takes longer for a familiar stimulus to become

8976-430: The most widely used treatments for anxiety disorders is exposure based therapy, which builds on the principles of fear extinction. The exact mechanisms underlying the developmental differences in fear extinction learning have not yet been discovered, although it has been suggested that age related differences in connectivity between the amygdala and medial prefrontal cortex can be one of the biological mechanisms underpinning

9078-466: The neural basis of conditioning has come from experiments on the sea slug, Aplysia . Most relevant experiments have used the classical conditioning procedure, although instrumental (operant) conditioning experiments have also been used, and the strength of classical conditioning is often measured through its operant effects, as in conditioned suppression (see Phenomena section above) and autoshaping . According to Pavlov, conditioning does not involve

9180-493: The neutral stimulus alone can elicit the state of fear. In the vocabulary of classical conditioning , the neutral stimulus or context is the "conditional stimulus" (CS), the aversive stimulus is the "unconditional stimulus" (US), and the fear is the "conditional response" (CR). Fear conditioning has been studied in numerous species, from snails to humans. In humans, conditioned fear is often measured with verbal report and galvanic skin response . In other animals, conditioned fear

9282-403: The normal monkeys learned to avoid them. He concluded that a key function of the amygdala was to connect external stimuli with aversive consequences. Following Weiskrantz's discovery many researchers used avoidance conditioning to study neural mechanisms of fear. Joseph E. LeDoux has been instrumental in elucidating the amygdala's role in fear conditioning. He was one of the first to show that

9384-409: The notion of physiological division of labor, which allowed to "compare and study living things as if they were machines created by the industry of man." Inspired in the work of Adam Smith , Milne-Edwards wrote that the "body of all living beings, whether animal or plant, resembles a factory ... where the organs, comparable to workers, work incessantly to produce the phenomena that constitute the life of

9486-409: The salience of the CS and the speed of learning for a given US. How the equation predicts various experimental results is explained in following sections. For further details, see the main article on the model. The R–W model measures conditioning by assigning an "associative strength" to the CS and other local stimuli. Before a CS is conditioned it has an associative strength of zero. Pairing the CS and

9588-429: The same time. For example: If a person hears a bell and has air puffed into their eye at the same time, and repeated pairings like this led to the person blinking when they hear the bell despite the puff of air being absent, this demonstrates that simultaneous conditioning has occurred. [REDACTED] Second-order or higher-order conditioning follow a two-step procedure. First a neutral stimulus ("CS1") comes to signal

9690-602: The same year, Charles Bell finished work on what would later become known as the Bell–Magendie law , which compared functional differences between dorsal and ventral roots of the spinal cord . In 1824, François Magendie described the sensory roots and produced the first evidence of the cerebellum's role in equilibration to complete the Bell–Magendie law. In the 1820s, the French physiologist Henri Milne-Edwards introduced

9792-401: The sound of a metronome ) and then gave the dog food; after a few repetitions, the dogs started to salivate in response to the stimulus. Pavlov concluded that if a particular stimulus in the dog's surroundings was present when the dog was given food then that stimulus could become associated with food and cause salivation on its own. In Pavlov's experiments the unconditioned stimulus (US) was

9894-415: The strength and/or frequency of the CR gradually. The speed of conditioning depends on a number of factors, such as the nature and strength of both the CS and the US, previous experience and the animal's motivational state. The process slows down as it nears completion. If the CS is presented without the US, and this process is repeated often enough, the CS will eventually stop eliciting a CR. At this point

9996-403: The temporal conditioning, as US such as food to a hungry mouse is simply delivered on a regular time schedule such as every thirty seconds. After sufficient exposure the mouse will begin to salivate just before the food delivery. This then makes it temporal conditioning as it would appear that the mouse is conditioned to the passage of time. [REDACTED] In this procedure, the CS is paired with

10098-421: The unconditioned stimulus is biologically potent (e.g., the taste of food) and the unconditioned response (UR) to the unconditioned stimulus is an unlearned reflex response (e.g., salivation). After pairing is repeated the organism exhibits a conditioned response (CR) to the conditioned stimulus when the conditioned stimulus is presented alone. (A conditioned response may occur after only one pairing.) Thus, unlike

10200-402: Was also the founder of experimental physiology. And for the next 1,400 years, Galenic physiology was a powerful and influential tool in medicine . Jean Fernel (1497–1558), a French physician, introduced the term "physiology". Galen, Ibn al-Nafis , Michael Servetus , Realdo Colombo , Amato Lusitano and William Harvey , are credited as making important discoveries in the circulation of

10302-955: Was founded in 1887 and included only men in its ranks. In 1902, the American Physiological Society elected Ida Hyde as the first female member of the society. Hyde, a representative of the American Association of University Women and a global advocate for gender equality in education, attempted to promote gender equality in every aspect of science and medicine. Soon thereafter, in 1913, J.S. Haldane proposed that women be allowed to formally join The Physiological Society , which had been founded in 1876. On 3 July 1915, six women were officially admitted: Florence Buchanan , Winifred Cullis , Ruth Skelton , Sarah C. M. Sowton , Constance Leetham Terry , and Enid M. Tribe . The centenary of

10404-410: Was provided by animal experimentation . Due to the frequent connection between form and function, physiology and anatomy are intrinsically linked and are studied in tandem as part of a medical curriculum. Involving evolutionary physiology and environmental physiology , comparative physiology considers the diversity of functional characteristics across organisms. The study of human physiology as

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