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Sequential Interplay of Nicotinic and GABAergic Signaling Guides Neuronal Development
Zhaoping Liu,Robert A. Neff,Darwin K. Berg*
GABA (-aminobutyric acid), the major inhibitory transmitterin the brain, goes through a transitory phase of excitationduring development. The excitatory phase promotes neuronal growthand integration into circuits. We show here that spontaneousnicotinic cholinergic activity is responsible for terminatingGABAergic excitation and initiating inhibition. It does so bychanging chloride transporter levels, shifting the driving forceon GABA-induced currents. The timing of the transition is critical,because the two phases of GABAergic signaling provide contrastingdevelopmental instructions. Synergistic with nicotinic excitation,GABAergic inhibition constrains neuronal morphology and innervation.The results reveal a multitiered activity-dependent strategycontrolling neuronal development.
Division of Biological Sciences, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093–0357, USA.
* To whom correspondence should be addressed. Email: dberg{at}ucsd.edu
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[DOI: 10.1126/stke.3652006tw420] |Abstract »
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-aminobutyric acid), the major inhibitory transmitter in the brain, goes through a transitory phase of excitation during development. The excitatory phase promotes neuronal growth and integration into circuits. We show here that spontaneous nicotinic cholinergic activity is responsible for terminating GABAergic excitation and initiating inhibition. It does so by changing chloride transporter levels, shifting the driving force on GABA-induced currents. The timing of the transition is critical, because the two phases of GABAergic signaling provide contrasting developmental instructions. Synergistic with nicotinic excitation, GABAergic inhibition constrains neuronal morphology and innervation. The results reveal a multitiered activity-dependent strategy controlling neuronal development. 
