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Estimation of ambient GABA levels in layer I of the mouse neonatal cortex in brain slices
Author(s) -
Dvorzhak Anton,
Myakhar Olga,
Unichenko Petr,
Kirmse Knut,
Kirischuk Sergei
Publication year - 2010
Publication title -
the journal of physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.802
H-Index - 240
eISSN - 1469-7793
pISSN - 0022-3751
DOI - 10.1113/jphysiol.2010.187054
Subject(s) - gabaergic , gabaa receptor , gamma aminobutyric acid , inhibitory postsynaptic potential , glutamate receptor , neocortex , glutamate decarboxylase , vigabatrin , bicuculline , postsynaptic potential , extracellular , chemistry , neuroscience , gabab receptor , stimulation , biology , receptor , biochemistry , epilepsy , anticonvulsant , enzyme
GABAergic synapses on Cajal–Retzius neurons in layer I of the murine neocortex experience GABA B receptor (GABA B R)‐mediated tonic inhibition. Extracellular GABA concentration ([GABA] o ) that determines the strength of GABA B R‐mediated inhibition is controlled by GABA transporters (GATs). In this study, we hypothesized that the strength ofpresynaptic GABA B R activation reflects [GABA] o in the vicinity of synaptic contacts. Slices obtained from two age groups were used, namely postnatal days (P)2–3 and P5–7. GABAergic postsynaptic currents (IPSCs) were recorded using the whole‐cell patch‐clamp technique. Minimal electrical stimulation in layer I was applied to elicit evoked IPSCs (eIPSCs) using a paired‐pulse protocol. Three parameters were selected for comparison: the mean eIPSC amplitude, paired‐pulse ratio, and failure rate. When GAT‐1 and GAT‐2/3 were blocked by NO‐711 (10 μ m ) and SNAP‐5114 (40 μ m ), respectively, no tonic GABA B R‐mediated inhibition was observed. In order to restore the control levels of GABA B R‐mediated inhibition, 250 and 125 n m exogenous GABA was required at P2–3 and P5–7, respectively. Addition of 3‐mercaptopropionic acid, a glutamate decarboxylase inhibitor, did not significantly change the obtained values arguing against the suggestion that a mechanism different from GATs contributes to [GABA] o control. We conclude that juxtasynaptic [GABA] o is higher (about 250 n m ) at P2–3 than at P5–7 (about 125 n m ). As both radial cell migration and corticogenesis in general are strongly dependent on [GABA] o and the formation of the last layer 2/3 is finished by P4 in rodents, the observed [GABA] o reduction in layer I might reflect this crucial event in the cortical development.