Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.
Sequential Interplay of Nicotinic and GABAergic Signaling Guides Neuronal Development
Zhaoping Liu,
Robert A. Neff,
Darwin K. Berg*
Abstract:
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
The editors suggest the following Related Resources on Science sites:
In Science Signaling
EDITORS' CHOICE
Pamela J. Hines (12 December 2006) Sci. STKE2006 (365), tw420.
[DOI: 10.1126/stke.3652006tw420] |Abstract »
THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
Methamidophos Exposure During the Early Postnatal Period of Mice: Immediate and Late-Emergent Effects on the Cholinergic and Serotonergic Systems and Behavior.
C. S. Lima, A. C. Dutra-Tavares, F. Nunes, A. L. Nunes-Freitas, A. Ribeiro-Carvalho, C. C. Filgueiras, A. C. Manhaes, A. Meyer, and Y. Abreu-Villaca (2013)
Toxicol. Sci.
|Abstract »|Full Text »|PDF »
The dominant functional nicotinic receptor in progenitor cells in the rostral migratory stream is the {alpha}3{beta}4 subtype.
Expression of GABA Signaling Molecules KCC2, NKCC1, and GAD1 in Cortical Development and Schizophrenia.
T. M. Hyde, B. K. Lipska, T. Ali, S. V. Mathew, A. J. Law, O. E. Metitiri, R. E. Straub, T. Ye, C. Colantuoni, M. M. Herman, et al. (2011)
J. Neurosci.
31, 11088-11095
|Abstract »|Full Text »|PDF »
Prenatal Nicotine Exposure Increases GABA Signaling and Mucin Expression in Airway Epithelium.
Depolarizing Actions of GABA in Immature Neurons Depend Neither on Ketone Bodies Nor on Pyruvate.
R. Tyzio, C. Allene, R. Nardou, M. A. Picardo, S. Yamamoto, S. Sivakumaran, M. D. Caiati, S. Rheims, M. Minlebaev, M. Milh, et al. (2011)
J. Neurosci.
31, 34-45
|Abstract »|Full Text »|PDF »
Non-cell-autonomous factor induces the transition from excitatory to inhibitory GABA signaling in retina independent of activity.
Endogenous Signaling through {alpha}7-Containing Nicotinic Receptors Promotes Maturation and Integration of Adult-Born Neurons in the Hippocampus.
N. R. Campbell, C. C. Fernandes, A. W. Halff, and D. K. Berg (2010)
J. Neurosci.
30, 8734-8744
|Abstract »|Full Text »|PDF »
Lateral Mobility of Nicotinic Acetylcholine Receptors on Neurons Is Determined by Receptor Composition, Local Domain, and Cell Type.
C. C. Fernandes, D. K. Berg, and D. Gomez-Varela (2010)
J. Neurosci.
30, 8841-8851
|Abstract »|Full Text »|PDF »
A potential role for nerve growth factor in regulating the maturation of inhibitory neurotransmission..
D. L. Jones (2010)
J. Neurosci.
30, 6813-6814
|Full Text »|PDF »
How GABA generates depolarization.
N. C. Spitzer (2010)
J. Physiol.
588, 757-758
|Full Text »|PDF »
In the Adult Hippocampus, Chronic Nerve Growth Factor Deprivation Shifts GABAergic Signaling from the Hyperpolarizing to the Depolarizing Direction.
L. Lagostena, M. Rosato-Siri, M. D'Onofrio, R. Brandi, I. Arisi, S. Capsoni, J. Franzot, A. Cattaneo, and E. Cherubini (2010)
J. Neurosci.
30, 885-893
|Abstract »|Full Text »|PDF »
Characterization of Rhythmic Ca2+ Transients in Early Embryonic Chick Motoneurons: Ca2+ Sources and Effects of Altered Activation of Transmitter Receptors.
S. Wang, L. Polo-Parada, and L. T. Landmesser (2009)
J. Neurosci.
29, 15232-15244
|Abstract »|Full Text »|PDF »
Novel Repression of Kcc2 Transcription by REST-RE-1 Controls Developmental Switch in Neuronal Chloride.
M. Yeo, K. Berglund, G. Augustine, and W. Liedtke (2009)
J. Neurosci.
29, 14652-14662
|Abstract »|Full Text »|PDF »
The Potassium Chloride Cotransporter KCC-2 Coordinates Development of Inhibitory Neurotransmission and Synapse Structure in Caenorhabditis elegans.
J. E. Tanis, A. Bellemer, J. J. Moresco, B. Forbush, and M. R. Koelle (2009)
J. Neurosci.
29, 9943-9954
|Abstract »|Full Text »|PDF »
Expression of mutant {beta}2 nicotinic receptors during development is crucial for epileptogenesis.
I. Manfredi, A. D. Zani, L. Rampoldi, S. Pegorini, I. Bernascone, M. Moretti, C. Gotti, L. Croci, G. G. Consalez, L. Ferini-Strambi, et al. (2009)
Hum. Mol. Genet.
18, 1075-1088
|Abstract »|Full Text »|PDF »
Inhibition of 7-containing nicotinic ACh receptors by muscarinic M1 ACh receptors in rat hippocampal CA1 interneurones in slices.
Mammalian Nicotinic Acetylcholine Receptors: From Structure to Function.
E. X. Albuquerque, E. F. R. Pereira, M. Alkondon, and S. W. Rogers (2009)
Physiol Rev
89, 73-120
|Abstract »|Full Text »|PDF »
Neurogenic Role of the Depolarizing Chloride Gradient Revealed by Global Overexpression of KCC2 from the Onset of Development.
A. Reynolds, E. Brustein, M. Liao, A. Mercado, E. Babilonia, D. B. Mount, and P. Drapeau (2008)
J. Neurosci.
28, 1588-1597
|Abstract »|Full Text »|PDF »
Prenatal and Adolescent Exposure to Tobacco Smoke Modulates the Development of White Matter Microstructure.
L. K. Jacobsen, M. R. Picciotto, C. J. Heath, S. J. Frost, K. A. Tsou, R. A. Dwan, M. P. Jackowski, R. T. Constable, and W. E. Mencl (2007)
J. Neurosci.
27, 13491-13498
|Abstract »|Full Text »|PDF »
Cell-Autonomous Inhibition of {alpha}7-Containing Nicotinic Acetylcholine Receptors Prevents Death of Parasympathetic Neurons during Development.
GABAA Receptor-Mediated Signaling Alters the Structure of Spontaneous Activity in the Developing Retina.
C.-T. Wang, A. G. Blankenship, A. Anishchenko, J. Elstrott, M. Fikhman, S. Nakanishi, and M. B. Feller (2007)
J. Neurosci.
27, 9130-9140
|Abstract »|Full Text »|PDF »
Dendritic Ca2+ signalling due to activation of {alpha}7-containing nicotinic acetylcholine receptors in rat hippocampal neurons.
-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. 
