GABA as a Neurotransmitter and Neurogenic Signal

Abstract

γ‐Aminobutyric acid (GABA) is an amino acid formed enzymatically from glutamate during and after brain development. GABA helps to produce, position and differentiate nerve cells before it mediates modulatory signals between them.

Keywords: GAD 65; GAD 67; GABA; GABAA receptor channel; anaesthetics

Figure 1.

During development γ‐aminobutyric acid (GABA) becomes progressively more restricted to synapses. (a) Neurons cultured from the embryonic rat cortex recapitulate development in vivo. Here, embryonic neurons photographed with phase‐contrast optics at the light microscopic level are shown differentiating processes. (b) GABA, visualized using fluorescent antibodies that detect GABA (green), is widely distributed throughout most of many embryonic neurons. (c,d) After processes have differentiated into active networks, the number of GABA‐containing neurons decreases and GABA is restricted primarily to synapses, which appear as green spots. Bar, 20 μm. (Courtesy of Dragan Maric.)

Figure 2.

Model of the pentameric γ‐aminobutyric acid type A (GABAA) receptor channel complex. The five subunits (two α, two β and one γ) forming the pentameric complex presumed to form the GABAA receptor channel span the plasma membrane and interact with two accessory proteins, gephyrin and GABAA receptor‐associated protein (GABARAP), in the cytoplasm, which serve to target the complex to the membrane. Two GABA molecules bind to extracellular sites formed at the two interfaces between α and β subunits to transform the receptor into a channel. The tranquillizer midazolam targets a site formed at the interfaces between α and γ subunits. Other anaesthetics and a socially relevant drug such as ethanol bind elsewhere. (Courtesy of Neil Harrison and Andrew Jenkins.)

Figure 3.

During development, continuous GABAergic signalling is replaced by brief intermittent transients and γ‐aminobutyric acid (GABA) becomes a modulatory transmitter. (a) Neurons were cultured from the embryonic rat brain, then recorded individually with ion‐filled glass pipettes to reveal their membrane properties (ion currents and potentials). Newly developing neurons exhibit continuous rather than intermittent fluctuations in chloride ion flux and create a noisy trace of ion current flow. The noisy trace reflects GABA's continuous and random activation of many GABAA receptor channels. Superfusion of the neuronal surface with saline (stream) to disperse GABA molecules accumulating at receptors eliminates the noisy fluctuating signal. (b) The contributions of individual chloride ion channels contributing to the current flow, which are magnified from the end of the trace in (a), are indicated by the 14 evenly spaced dotted lines. The channels close in an all‐or‐none manner, as GABA is dispersed from GABAA receptor channels. (c) After synapses form, GABAergic signalling at GABA receptor channels becomes intermittent as spontaneous, rapidly rising, exponentially decaying transients appear. (d) Superimposition of individual transients shows signals of different amplitudes, reflecting activation of variable numbers of GABAA receptor channels by different numbers of GABA molecules released in an all‐or‐none manner. The rapid rising phases of the signals are due to the well synchronized opening of the channels following receptor activation by GABA. The exponential decay reflects the unbinding of GABA and closing of many channels. The frequency distribution in the numbers of channels opened for different durations thus underlies the GABAergic signal. (e) GABAergic modulatory signals (downward‐going transients) abort action potentials evoked by stimulatory current injections (rectangular pulses). (Figure contributed by Jean Vautrin.)

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Further Reading

Barker JL, Behar T and Li Y‐X et al. (1998) GABAergic cells and signals in CNS development. Perspectives on Developmental Neurobiology 5: 305–322.

Ben‐Ari Y (2001) Developing networks play a similar melody. Trends in Neurosciences 24: 353–360.

Ben‐Ari Y (2002) Excitatory actions of GABA during development: the nature of the nurture. Nature Neuroscience Reviews 3: 728–739.

Jonas P, Bischofberger J, Fricker D and Miles R (2004) Interneuron diversity series: Fast in: fast out – temporal and spatial signal processing in hippocampal interneurons. Trends in Neurosciences 27: 30–40.

Olsen RW and Martin DL (eds) (2000) GABA in the Nervous System: The View at Fifty Years. Philadelphia: Lippincott Williams & Wilkins.

Owens DF and Kriegstein AR (2002) Is there more to GABA than synaptic inhibition? Nature Neuroscience Reviews 3: 715–727.

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How to Cite close
Barker, Jeffery L(May 2005) GABA as a Neurotransmitter and Neurogenic Signal. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1038/npg.els.0000121]