Floyd Bloom Neurotransmission Neurons nerve

cells) communicate chemically by releasing and responding to a wide range of chemical substances, referred to in the aggregate as NEUROTRANSMITTERS. The process of neurotransmission refers to this form of chemical communication between cells of the central and peripheral nervous system at the anatomically specialized point of transmission, the SYNAPSE (synaptic junctions). Thus, it is convenient to conceive of ''the'' neurotransmitter for a specific instance of synaptic connections between neurons in one brain location (the source neurons) and their synaptic partner cells (the target neurons) in another neuronal location. For example, the phrase ''dopaminergic neurons of the nigro-accum-bens circuit'' refers to the DOPAMINE-transmitting synaptic connections between the brain neurons of the substantia nigra and their targets in the NUCLEUS ACCUMBENS. Current concepts of neurotransmission, however, require a broader view; they would consider as neurotransmitters all the chemical substances that a given neuron employs to signal the other neurons to which it is anatomically connected (its synaptic targets) and through which that neuron may also be able to influence other neuronal and nonneuronal cells in the adjacent spatial environment of its circuitry (nonsynaptic targets).

In some cases—more frequent in invertebrate nervous systems, in more primitive vertebrates, and in the embryonic nervous system than in the adult mammalian nervous system—neurons may also communicate "electrically," by direct ionic coupling between connected cells, through specialized forms of intercellular junctions referred to as "gap junctions,'' or electrotonic junctions. Such electro-tonic transmission sites are of relatively little direct concern to the actions of addictive drugs and ALCOHOL. In contrast, it is the more pervasive process of chemical neurotransmission that underlies the main molecular and cellular mechanisms by which addictive drugs act—and through which the nervous system exposed to such drugs undergoes the adaptations that may lead to DEPENDENCE, Habituation, Withdrawal, and the more enduring changes that persist after withdrawal from the once-dependent state.

The critical characteristic of a substance designated as a neurotransmitter is the manner in which it is made and secreted. To qualify as a neurotransmitter, the release of the substance must be coupled to neuronal activity according to two rather stringent functional rules (see Figure 1).

1. The transmitter substance must be synthesized by the transmitting neuron. In most cases, the substance is made well in advance and stored in small organelles (synaptic vesicles) within the terminal axons of the source neuron, ready for eventual release when called upon.

2. The transmitter substance must be released by that neuron through a special form of activity-dependent, calcium ion (Ca2+) -selective, excitation-secretion coupling. Substances released through other nonactivity-coupled and non-Ca2 +-coupled mechanisms may be regarded as excretion (as with metabolic byproducts to be degraded), rather than secretion.

The synaptic junction is the site at which the axons of the source neuron physically make most intimate contact with the target neuron to form an anatomically specialized junction; concentrated there are the proteins that mediate the processes of transmitter release (from the presynaptic neuron) and response (by the postsynaptic neuron). Indirect evidence for some neurotransmitter systems has suggested to some scientists a general concept of nonsynaptic interneuronal communication, sometimes also referred to as paracrine or volumetransmission communication, in which the neuro-transmitter released by a designated set of presyn-aptic terminals may diffuse to receptive neurons that are not in anatomic contact. The sets of chemical substances that neurons can secrete when they are active can also influence the non-neuronal cells, such as the cells of the vascular system (the glia) and the inflammatory-immune cells (the microglia).

The activity of neurons can also be modified by substances released from the non-neuronal cells of the central or peripheral nervous system, substances often termed neuromodulators. This same term, however, is frequently applied to the effects of neuron-produced transmitter substances whose mechanisms of action and whose time course of effect differ from those of the classic junctional neurotransmitter acetylcholine.

The current research on neurotransmitters and neuromodulators pertinent to drugs and alcohol is devoted to (1) understanding how exposure to addictive drugs may regulate the genes that control the synthesis, storage, release, and metabolism of known neurotransmitters; (2) identifying new substances that may be recognized as neurotransmit-ters, whose effects may be related to the effects of or reactions to addictive drugs and alcohol; (3) understanding the molecular events by which neurons and other cells react to neurotransmitters in both short-term and long-term time frames (a process often termed signal transduction, which cells of the nervous system share with most other cells of the body) and how these processes may themselves be perturbed by the influence of addictive drugs and alcohol; and (4) understanding the operations of neuronal communication in an inte-grative context of the circuits that release and respond to specific transmitters, and the way in which these neuronal circuits participate in defined types of behavior, either normal or abnormal.

Peripheral Neuropathy Natural Treatment Options

Peripheral Neuropathy Natural Treatment Options

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