Nervous system synaptic neurotransmission

The concept of chemical neurotransmission originated in the 1920s with the classic experiments of Otto Loewi (which were themselves inspired by a dream), who demonstrated that by transferring the ventricular fluid of a stimulated frog heart onto an unstimulated frog heart he could reproduce the effects of a (parasympathetic) nerve stimulus on the unstimulated heart (Loewi Navratil, 1926). Subsequently, it was found that acetylcholine was the neurotransmitter released from these parasympathetic nerve fibers. As well as playing a critical role in synaptic transmission in the autonomic nervous system and at vertebrate neuromuscular junctions (Dale, 1935), acetylcholine plays a central role in the control of wakefulness and REM sleep. Some have even gone as far as to call acetylcholine a neurotransmitter correlate of consciousness (Perry et al., 1999). 

Finally, perhaps one of the oddest of recent discoveries is that toxic gases, such as nitric oxide (NO) and carbon monoxide (CO), can act as dual first/second messengers in the nervous system (Haley, 1998). Our current ideas of how drugs affect the complex events and regulation of synaptic neurotransmission are very simplistic and the real situation is obviously vastly more complicated. Some of these issues will be addressed in more detail in Chapter 14. 

Neurotrophins influence neurotransmission and synaptic plasticity. The discovery that the neurotrophins have acute effects in the mature nervous system and can modulate synaptic efficiency has forced a substantial reevaluation of the role of these molecules in modulating the dynamic behavior of the nervous system [12]. 

Ionotropic glutamate receptors mediate fast excitatory neurotransmission in practically all areas of the central nervous system (CNS). They are also critical for both the induction and expression of synaptic plasticity, and have been implicated in diverse pathological conditions, such as epilepsy, ischemic brain damage, anxiety, and addiction. There are three subtypes of ionotropic glutamate receptors that are named after their high-affinity agonists as a-amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA), N-1nethyl-D-aspartate (NMDA), and kainate (KA) receptors (1). 

Abstract Neurotransmission in the nervous system is initiated at presynaptic terminals by fusion of synaptic vesicles with the plasma membrane and subsequent exocytic release of chemical transmitters. Currently, there are multiple methods to detect neurotransmitter release from nerve terminals, each with their own particular advantages and disadvantages. For instance, most commonly employed methods monitor actions of released chemical substances on postsynaptic receptors or artificial substrates such as carbon libers. These methods are closest to the physiological setting because they have a rapid time resolution and they measure the action of the endogenous neurotransmitters rather than the signals emitted by exogenous probes. However, postsynaptic receptors only indirectly report neurotransmitter release in a form modified by the properties of receptors themselves, which are often nonlinear detectors of released substances. Alternatively, released chemical substances... 

The synapse is a critical structure in the nervous system and serves as the communication link between neurons (Figure 11.5). Synapses in the mammalian CNS are chemical in nature. They possess three components (1) a presynaptic element, (2) a postsynaptic element, and (3) a synaptic cleft. At a typical synapse, neurotransmission requires four steps (1) synthesis and storage of neurotransmitter, (2) transmitter release, (3) receptor activation, and (4) transmitter inactivation. 

This pharmacological class is one of the most complex since its members act on a variety of newly discovered calcium channels within the central nervous system with either synaptic or somatic localization and numerous functions. Little is known about the impact of calcium antagonists on chemical neurotransmission, neuronal functions and intracellular calcium homeostasis, particularly in neurones and glial cells. This wide area of research and the action of these drugs on cerebral vascularization have been the subject of a number of recent reviews [95, 128-130]. For dihydropyridines, it is also important to note the peripheral (cardiovascular) effects which in turn affect the central nervous system. 

Introduction - In last year s chs terl, ray late colleague. Dr. Giaiman and 1 atten te3 to characterize the current status of research on brain neurotransmitter substances. The major topics of that chapter were the basic biochemistry and physiology underlying chemical neurotransmission in the central nervous system (CNS), including a criti of the recent technical ad ces. Because of the emphasis upon the basics of neurotransmitters, we could not dwell vpon the status of information regarding any core neurotransmitter or any one synaptic junction. Therefore, this chapter will deal with the current status of specific central neurotransmitters for particular neuronal junctions. 

Biogenic monoamine neurotransmitters, specifically serotonin, norepinephrine and dopamine, play a crucial role in various central nervous system (CNS) activities, and monoamine deficiency has been implicated in a variety of CNS disorders. One approach to enhance monoaminergic neurotransmission is by inhibiting its reuptake after release into the synaptic cleft. Drugs that block... 

Intercellular communication in the nervous system is typically mediated through synaptic transmission via the release of neurotransmitters and their subsequent binding to specific receptors. The transmitter-receptor interaction then elicits changes in ion channel permeability and/or second messenger formation in the innervated cell. Neurotransmitters can also interact with receptors located on the presynaptic terminal (either autoreceptors, which are activated by the same transmitter, or heteroreceptors, which are activated by a different transmitter released by a different neuron) to regulate the presynaptic function, often by influencing neurotransmitter release. Termination of synaptic neurotransmission depends upon the removal of neurotransmitter molecules from the synaptic cleft by either enzymatic degradation or by reuptake into the presynaptic terminal. 

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