Receptors

Neuroanatomical delineations based on receptor distributions have been popular in pharmacological and neuroanatomical studies since the late 1960s and 1970s, particularly with the development of autoradiographic techniques. As a clear advantage, receptors were often confined to a small area in the brain and thus differentiated specific neuronal projections with great accuracy. This has not only given neuroanato-mical delineations a greater precision and resolution than ever before but also helped our understanding of how drugs work in the brain. For example, neuroana-tomical maps of receptors not only reveal the presence of a receptor specific for a certain drug in the brain but also reveal the specific circuitry to which it belongs. This, in turn, points to a mechanism of drug action. For example, Paxinos and Watson originally delineated the intermediate reticular zone in the rat brain on the basis of a band of negative AChE staining between the gigantocellular and parvicellular reticular nuclei. The area remained ambiguous until another group of researchers demonstrated that the zone exclusively contains angiotensin II receptors in the rat and human brain. Intense angiotensin II receptor binding in the intermediate reticular zone and no binding in the neighboring gigantocellular or parvicellular nuclei revealed clear boundaries of the structure and un ambiguously pointed to its homology between rat and human.

The neurokinin B receptor (NK3) is an integral component of the neural circuitry of neurokinin B, which in turn is a member of the tachykinin family of peptides (also including substance P and neurokinin A). NK3 is also an important element of the hypotha-lamic neuronal circuitry regulating blood pressure. Recent studies used immunohistochemistry to reveal the distribution of NK3 in the human hypothalamus and to compare this with the distribution of the receptor in the rat hypothalamus, in which the structure-function associations are better studied. The strongest NK3-like immunoreactivity in the human hypothalamus was found in neurons of the paraventricular nucleus (Pa), specifically in the parvi-cellular and posterior Pa subnuclei, thus distinguishing these structural subcompartments (Fig. 5). Another prominent population of NK3-positive cells in the human hypothalamus was found in the perifornical nucleus, distinguishing it from the rest of the lateral hypothalamic area. In cross-species comparison there appeared to be a large degree of similarity in the distribution of NK3 in the human and rat hypothalamus.

In the past two decades, the technique of in situ hybridization became available, and with its myriad of probes it allowed further characterization of the cell groups (Fig. 6). The presence of mRNA indicates a condition for protein production within specific neurons. A clear advantage of the method is that the mRNA signal is quantifiable. The quantity of signal can then be compared across species or between human brains. The distribution of mRNA generally falls within the boundaries defined by chemoarchitec-ture but in some rare cases it has been known to differ with the location of the corresponding protein. As an alternative technique to histo- and immuno-histochemistry, in situ hybridization provides an important confirmation of existing neuroanatomical delineations.

In describing chemical neuroanatomy as a methodology to reveal the organization of the human brain, it is useful to demonstrate the application of the approach in specific areas of the brain.

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