- Dale's principle
In neuroscience, Dale's Principle (or Dale's Law) is a rule attributed to the English neuroscientist Henry Hallett Dale. The principle basically states that a neuron performs the same chemical action at all of its synaptic connections to other cells, regardless of the identity of the target cell. However, there has been disagreement about the precise wording.
Because of an ambiguity in the original statement, there are actually two versions of the principle, one that has been shown definitively to be false, and another that remains a valuable rule of thumb. The term "Dale's Principle" was first used by Sir John Eccles in 1954, in a passage reading, "In conformity with Dale's principle (1934, 1952) that the same chemical transmitter is released from all the synaptic terminals of a neurone…" Some modern writers have understood the principle to state that neurons release one and only one transmitter at all of their synapses. Others, including Eccles himself in later publications, have taken it to mean that neurons release the same set of transmitters at all of their synapses.
Dale himself never stated his "principle" in an explicit form. The source that Eccles referred to was a lecture published by Dale in 1934, called Pharmacology and nerve endings, describing some of the early research into the physiology of neurotransmission. At that time, only two chemical transmitters were known, acetylcholine and noradrenaline (then thought to be adrenaline). In the peripheral nervous system, cholinergic and adrenergic transmission were known to arise from different groups of nerve fibers. Dale was interested in the possibility that a neuron releasing one of these chemicals in the periphery might also release the same chemical at central synapses. He wrote:
It is to be noted, further, that in the cases for which direct evidence is already available, the phenomena of regeneration appear to indicate that the nature of the chemical function, whether cholinergic or adrenergic, is characteristic for each particular neurone, and unchangeable.
And near the end of the paper:
When we are dealing with two different endings of the same sensory neurone, the one peripheral and concerned with vaso-dilatation and the other at a central synapse, can we suppose that-the discovery and identification of a chemical transmitter of axon-reflex vasodilatation would furnish a hint as to the nature of the transmission process at a central synapse? The possibility has at least some value as a stimulus to further experiment.
With only two transmitter chemicals known to exist at the time, the possibility of a neuron releasing more than one transmitter at a single synapse did not enter anybody's mind, and so no care was taken to frame hypotheses in a way that took this possibility into account. The resulting ambiguity in the initial statements led to some confusion in the literature about the precise meaning of the principle. Nicoll and Malenka, for example, understood it to state that a neuron always releases one and only one neurotransmitter at all of its synapses. In this form it is certainly false. Many neurons are capable of releasing more than one neurotransmitter, in what is called "cotransmission". The discovery of this phenomenon was relatively recent: although there were earlier hints, the first formal proposal did not come until 1976. Recent studies in a myriad of systems have shown that most, if not all, neurons release several different chemical messengers.
In a 1976 publication, however, Eccles reinterpreted the principle in a subtly different way:
"I proposed that Dale’s Principle be defined as stating that at all the axonal branches of a neurone, there was liberation of the same transmitter substance or substances."
The addition of "or substances" is critical. With this change, the principle allows for the possibility of neurons releasing more than one transmitter, and only asserts that the same set are released at all synapses. In this form, it continues to be an important rule of thumb, with only a few known exceptions., including David Sulzer and Stephen Rayport's finding that dopamine neurons also release glutamate as a neurotransmitter, but at separate release sites. In modern neuroscience, neurons are often classified by their neurotransmitter and most important cotransmitter, for example striatal GABA neurons utilize either opioid peptides or substance P as the primary cotransmitter.
Neurons in a class without a subpopulation of inhibitory interneurons can release at least two neurotransmitters at the same time, the other being a cotransmitter, in order to provide the stabilizing negative feedback required for meaningful encoding. Examples include:
- GABA — glycine co-release.
- Dopamine — glutamate co-release.
- Acetylcholine — glutamate co-release.
- Acetylcholine (ACh) — vasoactive intestinal peptide (VIP) co-release.
- Acetylcholine (ACh) — calcitonin gene-related peptide (CGRP) co-release.
- Glutamate — dynorphin co-release (in Hippocampus).
- ^ Eccles, JC; Fatt P, Koketsu K (1954). "Cholinergic and inhibitory synapses in a pathway from motor-axon collaterals to motoneurones.". J Physiol (Lond) 126: 524–62.
- ^ Strata, P; Harvey R (1999). "Dale's principle.". Brain Res Bull 50 (5–6): 349–50. doi:10.1016/S0361-9230(99)00100-8. PMID 10643431.
- ^ a b c Dale, HH (1934). "Pharmacology and Nerve-endings (Walter Ernest Dixon Memorial Lecture): (Section of Therapeutics and Pharmacology)". Proc Roy Soc Med 28 (3): 319–30. PMC 2205701. PMID 19990108. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2205701.
- ^ The name "adrenaline" is used because this is a historical account. This chemical is now officially called epinephrine
- ^ Shepherd, GM (1988). Neurobiology. Oxford University Press. pp. 163. ISBN 9780195051711.
- ^ Nicoll, RA; Malenka RC (1998). "A tale of two transmitters". Science 281 (5375): 360–1. doi:10.1126/science.281.5375.360. PMID 9705712.
- ^ Burnstock, G (2004). "Cotransmission". Curr Op Pharmacol 4 (1): 47–52. doi:10.1016/j.coph.2003.08.001. PMID 15018838.
- ^ Trudeau, LE; Gutiérrez R (June 2007). "On cotransmission & neurotransmitter phenotype plasticity". Mol Interven 7 (3): 138–46. doi:10.1124/mi.7.3.5. PMID 17609520. http://molinterv.aspetjournals.org/cgi/pmidlookup?view=long&pmid=17609520.
- ^ Eccles, JC (1976). "From electrical to chemical transmission in the central nervous system". R Soc London Notes and Records (Lond) 30 (2): 219–30. doi:10.1098/rsnr.1976.0015.
- ^ Sossin, WS; Sweet-Cordero A, Scheller RH (1990). "Dale's hypothesis revisited: different neuropeptides derived from a common prohormone are targeted to different processes". Proc. Natl. Acad. Sci. U.S.A. 87 (12): 4845–8. doi:10.1073/pnas.87.12.4845. PMC 54215. PMID 2352952. http://www.pnas.org/content/87/12/4845.
- ^ Sulzer, D; Rayport S (2000). "Dale's principle and glutamate corelease from ventral midbrain dopamine neurons". Amino Acids 19 (1): 45–52. doi:10.1007/s007260070032. PMID 11026472. http://www.springerlink.com/content/yeubwa9u577w77am/.
- ^ Inhibitory cotransmission or after-hyperpolarizing potentials can regulate firing in recurrent networks with excitatory metabotropic transmission
Wikimedia Foundation. 2010.
См. также в других словарях:
Dale Carpenter — is an American legal commentator and Earl R. Larson Professor of Civil Rights and Civil Liberties Law at the University of Minnesota Law School. As a professor, Carpenter specializes in constitutional law, the First Amendment, Due Process and… … Wikipedia
Dale Petroskey — Dale A. Petroskey (born August 17, 1955) is the former Executive Vice President of Marketing for the Texas Rangers Baseball Club. He is a former executive of the National Baseball Hall of Fame and Museum and the National Geographic Society, and a … Wikipedia
Henry Hallett Dale — Born 9 June 1875(1875 06 09) London, England Died 23 July 1968(1968 07 23) … Wikipedia
Principe de Dale — Demande de traduction Dale s principle → … Wikipédia en Français
Stephen Dale Petit — (born 19 April, 1960) is a guitarist, singer and songwriter who is a pioneer in a genre called the New Blues, and a major architect for the New Blues Revolution.He is noted for his rock and roll associations with greats such as Eric Clapton and… … Wikipedia
Nellie Dale — Ellen Nellie Dale (February 14, 1865 – February 26, 1967) was a British school teacher who created one of the earliest books on teaching reading. The earliest school based literacy education was started by Dale at Wimbledon High School from… … Wikipedia
nervous system — Anat., Zool. 1. the system of nerves and nerve centers in an animal or human, including the brain, spinal cord, nerves, and ganglia. 2. a particular part of this system. Cf. autonomic nervous system, central nervous system, peripheral nervous… … Universalium
List of eponymous laws — This list of eponymous laws provides links to articles on laws, adages, and other succinct observations or predictions named after a person. In some cases the person named has coined the law – such as Parkinson s law. In others, the work or… … Wikipedia
Brain — This article is about the brains of all types of animals, including humans. For information specific to the human brain, see Human brain. For other uses, see Brain (disambiguation). A chimpanzee brain The brain is … Wikipedia
Nervous system — Nerve redirects here. For other uses, see Nerve (disambiguation). This article is about the nervous system. For parts of the nervous system commonly called nerves, see Peripheral nerve. Nervous system The Human N … Wikipedia