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ORGANIZATIONAL PRINCIPLES OF THE CNS

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The brain is a complex assembly of interacting neurons and nuclei that regulate their own and each other's activities in a dynamic fashion, generally through chemical neurotransmission. It is useful to examine the major anatomical regions of the CNS and their associations with specific neurotransmitter systems and the effect of pharmacological agents thereon.

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CELLULAR ORGANIZATION OF THE BRAIN

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Neurons. Neurons are classified according to function (sensory, motor, or interneuron), location, the identity of the transmitter they synthesize and release or the class or classes of receptor expressed on the cell surface. Neurons exhibit the cytological characteristics of highly active secretory cells with large nuclei: large amounts of smooth and rough endoplasmic reticulum; and frequent clusters of specialized smooth endoplasmic reticulum (Golgi complex), in which secretory products of the cell are packaged into membrane-bound organelles for transport from the perikaryon to the axon or dendrites. The sites of interneuronal communication in the CNS are termed synapses. Like peripheral "junctions," central synapses are denoted by accumulations of tiny (50-150 nm) synaptic vesicles. The proteins of these vesicles have specific roles in transmitter storage, vesicle docking, and secretion and re-storage of transmitter.

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Support Cells. Neurons in the CNS are outnumbered by support cells, including macroglia, microglia, vascular elements, the cerebrospinal fluid (CSF)-forming cells of the choroid plexus found within the intracerebral ventricular system, and the meninges, which cover the surface of the brain and comprise the CSF-containing envelope. Macroglia are the most abundant support cells; some are categorized as astrocytes (cells interposed between the vasculature and the neurons, often surrounding individual compartments of synaptic complexes). Astrocytes play a variety of metabolic support roles including furnishing energy intermediates and supplementary removal of neurotransmitters following release. The oligodendroglia, a second prominent category of macroglia, are myelin-producing cells. Myelin, made up of multiple layers of compacted membranes, insulate segments of axons bioelectrically and permit nondecremental propagation of action potentials. Microglia are derived from mesoderm and are related to the macrophage/monocyte lineage. Some microglia reside within the brain, while additional cells of this class may be recruited to the brain during periods of inflammation -following either microbial infection or brain injury.

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Blood-Brain Barrier. The blood-brain barrier (BBB) is an important boundary between the periphery and the CNS that forms a permeability barrier to the passive diffusion of substances from the bloodstream into the CNS. The BBB diminishes the rate of access of many chemicals from plasma to the brain and is the localization of several drug export systems in the cells that constitute the BBB (see Chapter 5). An exception exists for lipophilic molecules, which diffuse fairly freely across the BBB and accumulate in the brain.

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This barrier, nonexistent in the peripheral nervous system, is much less prominent in the hypothalamus and in several small, specialized organs (the circumventricular organs) lining the third and fourth ventricles of ...

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