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Figure 8 Diagram showing the organization of major cell groups in the developing human hypothalamus depicted at landmark stages of fetal differentiation. Grayscale represents hypothalamic structural entities revealed by cytoarchitecture of the neuroepithelial primordia and transient chemoarchitectonic labeling. Note that these diagrams are not to scale. (Reproduced from J. Comp. Neurol. with permission from John Wiley & Sons, Inc., 2002).

in the lateral hypothalamus, one containing orexin-and another expressing melanin-concentrating hormone. Functional evidence as well as the strong relationship of orexin and melanin-concentrating hormone containing cells in the lateral hypothalamus to both the NPY and agouti gene-related protein systems suggest an important role for these neuronal groups among hypothalamic networks regulating feeding. These findings reinforce the importance of comprehensive use of chemoarchitecture in comparative studies of the adult human brain.

Chemoarchitecture is also useful in the study of the fetal brain. Thus, several chemoarchitectonic studies of the human fetal hypothalamus reported on the development of the hypophyseal portal plasma system, CRF-containing circuitry, GRH neurons, and soma-tostatin-, oxytocin-, vasoperessin-, and neurophysin-containing cells. Another recent study has proved the benefits of using a combination of peptide, receptors, and structural and calcium-binding protein markers on a series of fetal brains at different stages of development to provide insight into the structural development of the human hypothalamus (Fig. 8). Substances that revealed some aspects of synaptogen-esis, such as GAP43 and SYN, and an antibody directed against a cell surface membrane glycoconju-gate, 3-fucosyl-N-acetyl-lactosamine (FAL or CD15) were also found to be useful in the delineation of developing hypothalamic cell groups.

In the fetus, the structural differentiation of the lateral and posterior hypothalamus is apparent at 9 weeks of gestation, when these structures are marked by strong immunoreactivity for GAP43, a nerve terminal membrane phosphoprotein associated with the development and restructuring of axonal connections. This suggests that within the hypothalamus, synaptogenesis is well under way in the lateral and posterior hypothalamic areas as early as 10 weeks of gestation. In addition, GAP43 immunoreactivity clearly reveals, at 13 weeks of gestation, the otherwise ill-defined bundle x, which separates LH ventrally from posterior hypothalamic area (PH) dorsomedial-ly. Following the emergence of GAP43, another significant event in the differentiation of the lateral and posterior hypothalamic areas is the appearance of large Cr- and Cb-immunoreactive neurons at 13 and 16 weeks of gestation, respectively, and their persistence into the postnatal period. The mature morphological appearance of these neurons is reached by approximately 16 weeks of gestation, when they spread far laterally, abutting the pallidum and dorsally mingling with the zona incerta. Observations from the human fetus are consistent with reports on Cb immunoreac-tivity in the developing rat hypothalamus suggesting similarities between the area in the rat and human. In human fetuses chemoarchitecture also reveals distinct differences between the constituent structures of the lateral hypothalamic zone. For example, cells in PH, but not LH, show FAL immunoreactivity from 18 weeks of gestation until birth. Furthermore, the LH area contains Cr- and Cb-positive neurons and GAP43 immunoreactivity early in fetal gestation, unlike the adjacent tuberomammillary nucleus, which acquires Cb-positive neurons only late in gestation.

The distinction between the perifornical hypothala-mic nucleus and lateral hypothalamic area in the rat has been demonstrated by chemoarchitectonic and functional studies. Until recently, the adult human perifornical nucleus was mainly defined by topographic criteria because cytoarchitectonically it largely resembles surrounding structures. According to a recent chemoarchitectonic study in the human fetus, perifornical hypothalamic nucleus (PeF) is formed as a result of passive displacement of LH neurons medially. The studies' conclusions were based on differentiation patterns of calbindin-, calretinin-, and neuromedin K receptor-immunoreactive neurons. Thus, during gestation, the neurons of the lateral hypothalamus, which develop early, are progressively displaced laterally by the successive waves of neurons of the midline and core zones, which develop later. In contrast to LH neurons, the neurons of the PeF that originate from the lateral hypothalamic zone remain anchored in the perifornical position, possibly by virtue of their dendrites invading the fornical bundle.

Aspergers Answers Revealed

Aspergers Answers Revealed

Learn How to Help, Understand amp Cope with your Aspergers Child from a UK Chartered Educational Psychologist. Before beginning any practice relating to Aspergers it is highly recommended that you first obtain the consent and advice of a qualified health,education or social care professional.

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