GABA Itself Promotes the Developmental Switch of Neuronal GABAergic Responses from Excitation to Inhibition

Program in Neuroscience, Division of Biology, University of California, San Diego, La Jolla, CA 92093, USA.
Cell (Impact Factor: 32.24). 06/2001; 105(4):521-32. DOI: 10.1016/S0092-8674(01)00341-5
Source: PubMed


GABA is the main inhibitory neurotransmitter in the adult brain. Early in development, however, GABAergic synaptic transmission is excitatory and can exert widespread trophic effects. During the postnatal period, GABAergic responses undergo a switch from being excitatory to inhibitory. Here, we show that the switch is delayed by chronic blockade of GABA(A) receptors, and accelerated by increased GABA(A) receptor activation. In contrast, blockade of glutamatergic transmission or action potentials has no effect. Furthermore, GABAergic activity modulated the mRNA levels of KCC2, a K(+)-Cl(-) cotransporter whose expression correlates with the switch. Finally, we report that GABA can alter the properties of depolarization-induced Ca(2+) influx. Thus, GABA acts as a self-limiting trophic factor during neural development.

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Available from: Alejandro F Schinder, Jan 02, 2015
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    • "These classical neurotransmitters could interact with NKCC1 and/or KCC2 and play a trophic role during development . GABA appears essential for the development of KCC2-dependent inhibition in the cortex and retina (Ganguly et al., 2001; Leitch et al., 2005). "
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    • "Another critical instance with regard to life stage-specifi cities is given by the developmental switch of neuronal GABAergic responses from excitation to inhibition. This switch is dependent on GABA-induced GABA A receptor activation (Ganguly et al. 2001). Therefore, interference with GABA receptors during development and after brain maturation (see AOP III) is likely to cause distinctly diff erent AOs (Westerholz et al. 2010). "
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    • "Data suggests that GABA release in the early developing cortex is able to facilitate the transition of cellular responses to GABA from depolarizing to hyperpolarizing (Ganguly et al., 2001). Although this is mainly hypothesized to be an action potential-independent process (Ganguly et al., 2001), depolarization of GABAergic interneurons by thalamocortical afferents may increase the likelihood of this spontaneous release. Although controversial (Leinekugel et al., 1995; Ben-Ari et al., 1997), AMPA receptor-mediated excitation has been shown to play a role in the facilitation of GABA-induced depolarization. "
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