Nadarajah, Bagirathy; (1997) Gap junctions in the adult and developing cerebral cortex of the rat: Regional differences in their distribution and cellular localization of connexins. Doctoral thesis (Ph.D), UCL (University College London).

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Abstract

Neurons and glia of the cerebral cortex arise from the ventricular zone lining the telencephalic ventricles. Recent physiological evidence has demonstrated the presence of low resistance pathways between cortical neurons during corticogenesis and neuronal circuit formation, and proposed a role for gap junctions in the formation of neuronal domains which eventually may lead to the establishment of cortical columns. Gap junctions, the morphological correlates of electrical coupling and low resistance pathways, are plasma membrane channels composed of connexin proteins that connect the cytoplasm of contiguous cells. To date, thirteen mammalian connexins (Cxs) have been described in rodents of which Cxs 26, 32 and 43 are the major isoforms expressed in the adult and developing brain. Using immunocytochemistry, Western blotting, Northern blotting and electron microscopy (thin-section and freeze-fracture), the present study examines the frequency of gap junctions, the cell types involved in the formation of these junctions, gene expression of gap junction proteins, the connexins, and their distribution in the adult and developing cerebral cortex of the rat. The new findings that emerged from this study may be summarised as follows; 1) Cxs 26-, 32- and 43-immunoreactivities showed a differential expression in the developing and adult cortex. Connexin 26 was expressed in abundance during corticogenesis and neuronal circuit formation, whereas Cx 32 labelling was more robust after 2 weeks of postnatal life. Connexin 43 showed high levels of expression both in the developing and in the adult cortex. 2) In the adult, Cxs 43 and 32 showed regional differences in their expression. 3) Characterization of cortical cells demonstrated that Cx 26 was expressed by neurons, in contrast to the prevailing view that this connexin is expressed by ventricular zone cells during corticogenesis and subsequently in non-neuronal tissue. Similarly Cx 43, widely believed to be associated with astrocytes, was also localized in a population of neurons during development that persisted in the adult cortex. In addition, Cx 43 immunoreactivity was localized in radial glial fibres during late corticogenesis, when neurons are migrating to their destination in the cortical plate. 4) Conventional and freeze-fracture electron microscopy revealed the abundant presence of gap junctions in the adult neocortex consistent with the immunocytochemical findings. 5) Examination of the adult neocortex demonstrated homologous and heterologous gap junctions involving neurons and glia, of which the junctions between neurons and astrocytes are of interest as they may implicate the presence of a non-synaptic signalling pathways between these two cell types. These results show that gap junctions and their constituent connexins are abundantly present in the adult cerebral cortex and may provide a major nonsynaptic pathway between cortical cell types. In the developing cerebral cortex, gap junctions may be involved in co-ordinating important developmental events such as cell proliferation, layer specification, neuronal migration and, later, in the synchronisation of neuronal activity prior to the maturation of chemical synapses.

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