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Neurotransmitter 3D Animation
on Tuesday, December 21, 2010
Neurotransmitters are endogenous chemicals which transmit signals from a neuron to a target cell across a synapse. Neurotransmitters are packaged into synaptic vesicles clustered beneath the membrane on the presynaptic side of a synapse, and are released into the synaptic cleft, where they bind to receptors in the membrane on the postsynaptic side of the synapse. Release of neurotransmitters usually follows arrival of an action potential at the synapse, but may also follow graded electrical potentials. Low level "baseline" release also occurs without electrical stimulation. Neurotransmitters are synthesized from plentiful and simple precursors, such as amino acids, which are readily available from the diet and which require only a small number of biosynthetic steps to convert. The chemical identity of neurotransmitters is often difficult to determine experimentally. For example, it is easy using an electron microscope to recognize vesicles on the presynaptic side of a synapse, but it may not be easy to determine directly what chemical is packed into them. The difficulties led to many historical controversies over whether a given chemical was or was not clearly established as a transmitter. In an effort to give some structure to the arguments, neurochemists worked out a set of experimentally tractable rules. According to the prevailing beliefs of the 1960s, a chemical can be classified as a neurotransmitter if it meets the following conditions: * There are precursors and/or synthesis enzymes located in the presynaptic side of the synapse. * The chemical is present in the presynaptic element. * It is available in sufficient quantity in the presynaptic neuron to affect the postsynaptic neuron; * There are postsynaptic receptors and the chemical is able to bind to them. * A biochemical mechanism for inactivation is present. There are many different ways to classify neurotransmitters. Dividing them into amino acids, peptides, and monoamines is sufficient for some classification purposes. Major neurotransmitters: * Amino acids: glutamate, aspartate, D-serine, γ-aminobutyric acid (GABA), glycine * Monoamines and other biogenic amines: dopamine (DA), norepinephrine (noradrenaline; NE, NA), epinephrine (adrenaline), histamine, serotonin (SE, 5-HT), melatonin * Others: acetylcholine (ACh), adenosine, anandamide, nitric oxide, etc. In addition, over 50 neuroactive peptides have been found, and new ones are discovered regularly. Many of these are "co-released" along with a small-molecule transmitter, but in some cases a peptide is the primary transmitter at a synapse. β-endorphin is a relatively well known example of a peptide neurotransmitter; it engages in highly specific interactions with opioid receptors in the central nervous system. Single ions, such as synaptically released zinc, are also considered neurotransmitters by some[by whom?], as are some gaseous molecules such as nitric oxide (NO) and carbon monoxide (CO). These are not classical neurotransmitters by the strictest definition, however, because although they have all been shown experimentally to be released by presynaptic terminals in an activity-dependent way, they are not packaged into vesicles. By far the most prevalent transmitter is glutamate, which is excitatory at well over 90% of the synapses in the human brain. The next most prevalent is GABA, which is inhibitory at more than 90% of the synapses that do not use glutamate. Even though other transmitters are used in far fewer synapses, they may be very important functionally—the great majority of psychoactive drugs exert their effects by altering the actions of some neurotransmitter systems, often acting through transmitters other than glutamate or GABA. Addictive drugs such as cocaine and amphetamine exert their effects primarily on the dop
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M.Torabi Nami MD, PhDc Department of Neuroscience Institute for Cognitive Science Studies (ICSS), Tehran 15948 Iran Torabi_m@iricss.org Abstract Sleepiness, tiredness and fatigue are complaints which must be thoroughly analyzed to eliminate blur and ambiguity. Physiological sleepiness (“sleep pressure”) increases while being awake and additionally underlies the circadian rhythm with a lower threshold to fall asleep during night time. Excessive daytime sleepiness (EDS) is considered normal only after sleep deprivation. Clinically, EDS manifests by frequents daytime napping and/or reduced alertness with automatic behavior or - in its extreme form - in recurrent attacks of sudden, uncontrollable compulsion to sleep also in inappropriate situations (= “sleep attacks”). EDS is “objectively” addressed by measuring the mean sleep latency to four to five nap opportunities throughout the day using the multiple sleep latency test (MSLT) or the maintenance of wakefulness test (MWT). EDS denotes both, a ready entrance into sleep as well as difficulty in staying awake during daytime or accordingly in inappropriate situations. These two partially independent aspects of EDS are separately assessed by the “passive” MSLT and the “active” MWT respectively. For that reason the MSLT and MWT only weakly correlate with each other when tested over a broad range of patients with EDS. It is important to keep in mind, that these tests are importantly influenced by a great variety of factors such as mood, anxiety, and motivation. “Vigilance” comprises wakefulness, alertness and attention and therefore is more than just the reciprocal to sleepiness. Cognitive performance tasks such as Steer Clear Reaction Time Test (SCRTT) or driving simulators require the complete integrity of vigilance to achieve normal results. Hypersomnia is usually broadly defined as the combination of abnormally prolonged night-time sleep (regularly >10 h) with EDS during ≥1 months. On the other hand, the term hypersomnia has also been used in a narrower scene for the isolated abnormality of a prolonged night-time sleep need (>10 h). “Tiredness”, also in colloquial language often used for sleepiness, in a broader sense also describes the feeling of lack of energy, motivation and initiative. These patients seek rest rather than sleep. They often cannot fall asleep when given the opportunity in spite of feeling tired, and hence, in an MSLT, do not show an abnormally short sleep latency. Furthermore, tiredness (and fatigue) as opposed to sleepiness has a mental (“central”) and physiological (bodily or “peripheral”) component, which the patients can readily distinguish. Patients with insomnia, mild sleep apnea syndrome, or depression rather suffer from mental tiredness than sleepiness during the day. The simple subjective self-assessment using the Epworth Sleepiness Scale (ESS) quite reliably differentiates between sleepiness and mental tiredness (without sleepiness), which makes it a widely used test. The term “fatigue” is also heterogeneously used. In physiology the “fatigue” implied a “time on task performance decrement” to describe decreasing muscle force during a sustained physical effort. In clinical medicine one distinguishes physical (“peripheral”) from mental (“central”) fatigue and the term usually denotes a chronic and more abnormal situation than tiredness. In a broad sense “fatigue” implies a deficiency in coping satisfactorily with mental and physical work load. The chronic fatigue syndrome entails both mental as well as a physical fatigue (so called “leaden paralysis” of limbs). Depressive states are often associated with insomnia and fatigue, but there are also cases with hypersomnia rather than insomnia ( non organic hypersomnia , “atypical depression” or “hypersom