RESUMO
The formation of functional neural networks requires precise regulation of the growth and branching of the terminal arbors of axons, processes known to be influenced by early network electrical activity. Here we show that a rule of activity-based competition between neighbouring axons appears to govern the growth and branching of retinal ganglion cell (RGC) axon arbors in the developing optic tectum of zebrafish. Mosaic expression of an exogenous potassium channel or a dominant-negative SNARE protein was used to suppress electrical or neurosecretory activity in subsets of RGC axons. Imaging in vivo showed that these forms of activity suppression strongly inhibit both net growth and the formation of new branches by individually transfected RGC axon arbors. The inhibition is relieved when the activity of nearby 'competing' RGC axons is also suppressed. These results therefore identify a new form of activity-based competition rule that might be a key regulator of axon growth and branch initiation.
Assuntos
Axônios/fisiologia , Rede Nervosa/citologia , Rede Nervosa/crescimento & desenvolvimento , Células Ganglionares da Retina/citologia , Animais , Encéfalo/citologia , Encéfalo/crescimento & desenvolvimento , Cálcio/metabolismo , Sinalização do Cálcio , Movimento Celular , Forma Celular , Humanos , Proteínas de Membrana/genética , Proteínas de Membrana/metabolismo , Modelos Neurológicos , Canais de Potássio Corretores do Fluxo de Internalização/genética , Canais de Potássio Corretores do Fluxo de Internalização/metabolismo , Terminações Pré-Sinápticas/metabolismo , Proteínas R-SNARE , Células Ganglionares da Retina/fisiologia , Peixe-Zebra/embriologia , Peixe-Zebra/genéticaRESUMO
Recent imaging studies show that the formation of neural connections in the central nervous system is a highly dynamic process. The iterative formation and elimination of synapses and neuronal branches result in the formation of a much larger number of trial connections than is maintained in the mature brain. Neural activity modulates development through biasing this process of formation and elimination, promoting the formation and stabilization of appropriate synaptic connections on the basis of functional activity patterns.
