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 γ-aminobuytric acid (GABA), which operates primarily via chloride-permeable GABAAreceptor 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 synaptic plasticity and pathological insults, notably seizures of the immature brain. In conclusion, it is suggested that an evolutionary preserved role for excitatory GABA in immature cells provides an important mechanism in the formation of synapses and activity in neuronal networks.

Early‐life single‐episode sevoflurane exposure impairs social behavior and cognition later in life

“…GABA exerts excitatory signaling in neurons during early development and then undergoes a switch to inhibition (Ben‐Ari et al. 2007). In rodents, the GABA switch extends over the entire second postnatal week and is completed in the third week.…”

Regulation of neuronal chloride homeostasis by neuromodulators

“…However, unlike glutamate, which maintains its function as an excitatory neurotransmitter throughout its lifetime, there is a change in the function of GABA across development and during pathophysiological states (Ben‐ari et al . 2007). GABA is an excitatory neurotransmitter during embryonic development, and an inhibitory neurotransmitter in the adult brain.…”

GABA transaminases from Saccharomyces cerevisiae and Arabidopsis thaliana complement function in cytosol and mitochondria

“…The role of GABA as a neuronal transmission inhibitor is well established in animals and GABA-T and SSADH defects result in non-specific neurological disorders, including psychomotor retardation, language delay and seizures (Hogema et al, 2001;Gropman, 2003), GABA also possesses excitory actions in immature neurons (Ben-Ari et al, 2007).…”