Jean-Pierre Bourgeois | PubMed Health

PubMed2005

[Brain synaptogenesis and epigenesis].

Synaptic plasticity, or epigenesis, is present and varies throughout the whole life of the cerebral cortex. The adult synapse is formed of large and variable proteins assemblies acting as molecular switches leading to many distinct functional states. In the flow of activity circulating through the synaptic circuits, these multiple synaptic states transitions are modulated by the levels and sequences of activations of the pre- and post-synaptic domains. The efficiency of synaptic transmission is also modulated by competition and/or cooperativity with neighbouring synapses, and by many neuromodulations. Some transitions eventually lead to synaptogenesis. In the adult cerebral cortex, synaptogenesis remains a local event; axonal and dendritic arbors are not reshaped. On the contrary, during pre- and post-natal synaptogenesis, the same molecular mechanisms lead to a significant reorganization of the axonal and dendritic arbors. Early in the development, synapses are generated and differentiate under the control of robust mechanisms governed by genes. Then, during the critical periods, extending from the end of gestation to the end of puberty, the refinement of the synaptic architecture becomes experience-expectant. This "epigenetic opening" of synaptogenesis to environment is maximal in the human brain. It is the source of the exceptional cognitive adaptability of our species, and possibly one of its major fragility. Epigenetic manipulations of these critical periods are undertaken, allowing restoration of synaptic plasticity also in the adult brain.

Brain↗

PubMed2003

Localization of [3H]nicotine, [3H]cytisine, [3H]epibatidine, and [125I]alpha-bungarotoxin binding sites in the brain of Macaca mulatta.

We determined the localization of [(3)H]nicotine, [(3)H]cytisine, [(3)H]epibatidine, and [(125)I]alpha-bungarotoxin binding sites in the brain of rhesus monkey by means of receptor autoradiography. The labelings by [(3)H]nicotine, [(3)H]cytisine, and [(3)H]epibatidine were highly concordant, except for epibatidine. Layer IV of some cortical areas, most thalamic nuclei, and presubiculum displayed high levels of labeling for the three ligands. Moderate levels of binding were detected in the subiculum, the septum, and the mesencephalon. Low levels were present in layers I-II and VI of the cortex, the cornu Ammonis, the dentate gyrus, and the amygdala. In addition, the level of epibatidine labeling was very high in the epithalamic nuclei and the interpeduncular nucleus, whereas labeling by nicotine and cytisine was very weak in the same regions. The distribution of [(125)I]alpha-bungarotoxin binding differed from the binding of the three agonists. The labeling was dense in layer I of most cortical areas, dentate gyrus, stratum lacunosum-moleculare of CA1 field, several thalamic nuclei, and medial habenula. A moderate labeling was found in layers V and VI of the prefrontal and frontal cortices, layer IV of primary visual cortex, amygdala, septum, hypothalamus, and some mesencenphalic nuclei. A weak signal was also detected in subiculum, claustrum, stratum oriens, and stratum lucidum of cornu Ammonis and also in some mesencephalic nuclei. The distribution of nicotine, cytisine, and epibatidine bindings corresponds broadly to the patterns observed in rodents, with the marked exception of the epithalamus. However, in monkey, those distributions match the distribution of alpha2 messenger RNA, rather than that of alpha4 transcripts as it exists in rodent brains. The distribution of the binding sites for alpha-bungarotoxin is larger in the brain of rhesus monkeys than in rodent brain, suggesting a more important role of alpha7 receptors in primates.

Alkaloids↗