GABA: A Pioneer Transmitter That Excites Immature Neurons and Generates Primitive Oscillations
Abstract
Developing networks follow common rules to shift from silent cells to coactive networks that operate via thousands of synapses. This review deals with some of these rules and in particular those concerning the crucial role of the neurotransmitter gamma-aminobuytric acid (GABA), which operates primarily via chloride-permeable GABA(A) receptor channels. In all developing animal species and brain structures investigated, neurons have a higher intracellular chloride concentration at an early stage leading to an efflux of chloride and excitatory actions of GABA in immature neurons. This triggers sodium spikes, activates voltage-gated calcium channels, and acts in synergy with NMDA channels by removing the voltage-dependent magnesium block. GABA signaling is also established before glutamatergic transmission, suggesting that GABA is the principal excitatory transmitter during early development. In fact, even before synapse formation, GABA signaling can modulate the cell cycle and migration. The consequence of these rules is that developing networks generate primitive patterns of network activity, notably the giant depolarizing potentials (GDPs), largely through the excitatory actions of GABA and its synergistic interactions with glutamate signaling. These early types of network activity are likely required for neurons to fire together and thus to "wire together" so that functional units within cortical networks are formed. In addition, depolarizing GABA has a strong impact on synap…
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During this period, GABA-induced currents are the main source of depolarization and are critical for the generation of synchronized patterns of activity that characterize developing networks.
“During this period, GABAinduced currents are the main source of depolarization and are critical for the generation of synchronized patterns of activity that characterize developing networks 26 .”
From Developmental timing and critical windows for the treatment of psychiatric disorders (2016) · cites this paper as [26]
In both the neocortex and hippocampus, network oscillations dependent on glutamatergic and GABAergic synapses emerge near the middle of the first postnatal week.
“In both the neocortex and hippocampus, network oscillations dependent on glutamatergic and GABAergic synapses emerge near the middle of the first postnatal week”
From Hippocampal GABAergic Inhibitory Interneurons (2017) · cites this paper as [92]
In principal cells, the earliest synaptic currents detected postnatally are mediated by GABAARs and NMDARs; AMPAR-mediated currents are initially absent and appear later during the first postnatal week.
“In PCs, the earliest synaptic currents detected postnatally are mediated by GABAARs and NMDARs; AMPA receptor (AMPAR)-mediated currents are initially absent, only appearing later during the first postnatal week”
From Hippocampal GABAergic Inhibitory Interneurons (2017) · cites this paper as [92]
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- Authors
- Ben-Ari, Y., Gaiarsa, J.-L., Tyzio, R., & Khazipov, R.
- ORCID
- Tyzio, Roman
- Venue
- Physiological Reviews
- Publisher
- American Physiological Society
- Published
- 2007-10
- Volume
- 87
- Issue
- 4
- Pages
- 1215-1284
- ISSN
- 0031-9333 (ISSN-L)
- 1522-1210
- OpenAlex
- W2117329255
- Cited by
- 1,304
- References
- 18
- Citations by year
- 2026: 35 · 2025: 41 · 2024: 45 · 2023: 54 · 2022: 69 · 2021: 72 · 2020: 107 · 2019: 56 · 2018: 52 · 2017: 66 · 2016: 65 · 2015: 82 · 2014: 65 · 2013: 108 · 2012: 90
- FWCI
- 6.11
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Physiological Reviews (publishedVersion)
- PubMed (publishedVersion)
- HAL (submittedVersion)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Neuroscience › Cognitive Neuroscience › Neural dynamics and brain function
- Health Sciences › Medicine › Psychiatry and Mental health › Epilepsy research and treatment
- Keywords
- GABA, immature neurons, intracellular chloride concentration, giant depolarizing potentials, network oscillations, synaptogenesis, glutamate signaling, neuronal migration, cell cycle, synaptic plasticity, seizures
- MeSH terms
- Animals, gamma-Aminobutyric Acid, Synaptic Transmission, Neuronal Plasticity, Neurons, Seizures, Synapses, Signal Transduction
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