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| Norbert Ulfig |
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RG Neuroembryology, Department of Anatomy, University of Rostock, GERMANY
e-mail: norbert.ulfig@med.uni-rostock.de |
Presentation: |
| 2002-10-09, 09:00-09:45 |
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| Development of the human amygdala with special reference to the ganglionic eminence. |
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| Recently evidence has been provided that alterations in the development of the amygdala may be of pivotal importance in the pathogenesis of psychiatric diseases. Therefore, the fetal development of the human amygdala has been investigated with special reference to major ontogenetic events and the ganglionic eminence which is the source of the amygdaloid neurons. In the 5th gestational month the inferior portion of the amygdala reveals cell-dense columns which merge with the ganglionic eminence. Within these columns vimentin-positive fibers are present; these fibers most probably represent radial glial fibers which provide a scaffold for migrating neurons. Thus, the cell-dense columns may be regarded as migrational routes. In the 6th and 7th month, these columns gradually disappear and merging between the amygdala and the ganglionic eminence can no longer be detected. So, a distinct cytoarchitectonic reorganization takes place. In MAP (microtubule-associated protein) 1b and SNAP (synaptosomal-associated protein) 25-immunopreparations fibers within the basolateral amygdala are observed to course towards the mantle zone of the ganglionic eminence. At this location an intense punctate MAP1b- and SNAP25-immunolabelling is present. This punctate labelling is indicative of fiber termination. Thus, the mantle region of the ganglionic eminence is likely to be an intermediate target for growing amygdaloid axons which later grow towards the cerebral cortex. Using anti-calbindin and anti-calretinin migrating and immature amygdaloid neurons can be shown in the 5th month. Migrating calretinin-positive neurons also express ARVCF (armadillo repeat gene deleted in velo-cardio-facial syndrome) which belongs to the family of armadillo repeat proteins. It is involved in the modulation of the strength of cell-cell adhesion essential in cell migration. From the 8th month onwards various non-pyramidal neurons and pyramidal neurons are immunostained. A transient expression of calretinin in pyramidal neurons (i.e. projection neurons) is seen. Double-labellings showed that calbindin and calretinin are mainly contained in different subsets of non-pyramidal neurons (i.e. interneurons). The sequential occurrence of afferents within the amygdala can be visualized with the aid of anti-GAP (growth-associated protein) 43. Distinct changes in the distribution of GAP43-positive structures are observed when comparing immunopreparation of the 5th and 8th month. It is apparent that the amygdala has reached a high degree of maturity in the 8th month, for instance the late occurrence of GAP43-positive puncta which can be correlated to synaptogenesis within the lateral and basal nucleus. At this developmental stage AKAP (a kinase anchoring protein) 79 which is enriched in postsynaptic densities displays a characteristic expression pattern within the amygdaloid nuclei. The latter largely corresponds to the distribution pattern of the glutamate receptor NMDAR1. Thus, AKAP79 may have a preference for anchoring enzymes to glutamate receptors. On the whole, the results summerized here provide a basis for investigations on subtle changes that may have been overlooked in developmental disorders so far (for instance autism). Moreover, these results are of importance for studies aiming at investigating the prenatal roots of neuropsychiatric diseases, such as schizophrenia. |
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