GABAergic control of retinal ganglion cell dendritic development

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  2. Francois Chabrol
  3. Dr Evelyne Sernagor
Author(s)Chabrol F, Eglen SJ, Sernagor E
Publication type Article
ISSN (print)0306-4522
ISSN (electronic)1873-7544
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Developing GABAergic neurons mature long before excitatory neurons, and early GABAA activity exerts important paracrine effects while neurons extend dendrites and axons and they establish neural connections. One of the unique features of early GABAA activity is that it induces membrane depolarization and Ca2+ influx and it shifts to inhibition when networks mature. Although it has been demonstrated in several systems that early GABAA signalling plays a fundamental role in guiding neurite outgrowth, it has never been investigated in the retina. Here we show that chronic GABAergic activity is required for the stabilization and maintenance of newly formed dendritic branches in developing turtle retinal ganglion cells (RGCs) in ovo. Blocking GABAA receptors with bicuculline or inhibiting GABA synthesis with L-allylglycine have contrasting effects on dendritic growth and branching in biocytin-labeled RGCs. Dendritic arbor reconstruction shows that bicuculline induces dendritic branch loss without global change in the extent of dendritic fields whilst L-allylglycine causes the entire tree to shrink. At the same time, multielectrode array recordings and Ca2+ imaging show that L-allylglycine has similar effects to bicuculline (Leitch et al., 2005) on overall network excitability, preventing the disappearance of immature retinal waves of activity and the GABAergic polarity shift. This study demonstrates for the first time that GABA plays an important role in vivo in stabilizing developing dendrites into mature arbors in the retina. However, the way GABA influences dendritic growth appears to be driven by complex mechanisms that cannot be explained solely on the basis of overall network activity levels.
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