Sequential interplay of nicotinic and GABAergic signaling guides neuronal development
Abstract
GABA (gamma-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.
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Disrupting nicotinic receptor signaling delays the switch from GABA-mediated excitation to inhibition.
“Disrupting nAChR signaling delays the switch from GABA-mediated excitation to inhibition.”
From Acetylcholine as a Neuromodulator: Cholinergic Signaling Shapes Nervous System Function and Behavior (2012) · cites this paper as Liu et al., 2006
One fundamental role for acetylcholine signaling through nicotinic receptors is to regulate the timing of expression of the chloride transporter that is necessary for the ability of GABA to hyperpolarize, and therefore inhibit, central neurons.
“For example, one fundamental role for ACh signaling through nAChRs is to regulate the timing of expression of the chloride transporter that is necessary for the ability of GABA to hyperpolarize, and therefore inhibit, central neurons (Liu et al., 2006).”
From Acetylcholine as a Neuromodulator: Cholinergic Signaling Shapes Nervous System Function and Behavior (2012) · cites this paper as Liu et al., 2006
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References 27 · Cited by 227
- Authors
- Liu, Z., Neff, R. A., & Berg, D. K.
- Affiliations
- University of California San Diego (US)
- Corresponding author
- Berg, Darwin K.
- Venue
- Science
- Published
- 2006-12-08
- Volume
- 314
- Issue
- 5805
- Pages
- 1610-1613
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- OpenAlex
- W2083548678
- Cited by
- 227
- References
- 27
- Citations by year
- 2026: 3 · 2025: 3 · 2024: 9 · 2023: 7 · 2022: 5 · 2021: 7 · 2020: 4 · 2019: 10 · 2018: 12 · 2017: 14 · 2016: 9 · 2015: 9 · 2014: 12 · 2013: 18 · 2012: 23
- FWCI
- 5.43
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Science (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute of Neurological Disorders and Stroke (NS 035469, NS012601, R01NS012601, R01NS035469)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Nicotinic Acetylcholine Receptors Study
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Keywords
- nicotinic acetylcholine receptors, GABAergic inhibition, neuronal development, chloride transporters, inhibitory interneurons, neuronal morphology, innervation, activity-dependent development
- MeSH terms
- K Cl- Cotransporters, Animals, Cadmium, Calcium, Chick Embryo, Chlorides, gamma-Aminobutyric Acid, Ganglia, Parasympathetic, Hippocampus, Mice, Inbred C57BL, Synaptic Transmission, Neurons, Nicotine, Receptors, Nicotinic, Recombinant Fusion Proteins, Transfection, Signal Transduction, Mice, Knockout, Patch-Clamp Techniques, Nicotinic Antagonists, Symporters, Sodium-Potassium-Chloride Symporters, Mice, Solute Carrier Family 12, Member 2, alpha7 Nicotinic Acetylcholine Receptor
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