A wealth of recent findings has demonstrated the outmost importance of neural activity the establishment of neural networks. GABAergic activity plays a central role in this process by exerting the earliest excitatory drive onto developing neurons. Progenitor proliferation, neuronal migration, arbour elaboration and development are all influenced by GABA. This early excitatory effect is due to an elevated intracellular concentration of C1- ([C1-]in), resulting in an outwardly directed driving force for C1- that renders GABAa transmission excitatory. During late developmental stages, as a result of an ontogenic decrease in [C1-]in that switches the polarity of the driving force for C1-, GABA becomes inhibitory. The commonly accepted hypothesis concerning the mechanisms underlying the shift in [C1-]n stipulates that the Na+/K+/C1- cotransporter 1 (NKCC1) accumulates C1- in embryonic neurons and that an ontogenic increase in the expression of the K+/C1- cotransporter 2 (KCC2) that extrudes C1- from adult neurons, induces the shift. A concurrent downregulation of NKCCl is also thought to participate in the shift. The switch of GABAergic polarity constitutes a major step in the maturation of neural networks.
| Identifer | oai:union.ndltd.org:bl.uk/oai:ethos.bl.uk:501150 |
| Date | January 2009 |
| Creators | Chabrol, Francois |
| Publisher | University of Newcastle Upon Tyne |
| Source Sets | Ethos UK |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
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