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The Journal of Neuroscience, April 19, 2006, 26(16):4216-4227; doi:10.1523/JNEUROSCI.0589-06.2006

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Cellular/Molecular
Ambient GABA Constrains the Strength of GABAergic Synapses at Cajal-Retzius Cells in the Developing Visual Cortex

Knut Kirmse and Sergei Kirischuk

Sensory and Developmental Physiology Group, Institute of Neurophysiology, Johannes-Mueller-Center of Physiology, Charité-University Medicine Berlin, 10117 Berlin, Germany

Correspondence should be addressed to Dr. Sergei Kirischuk, Sensory and Developmental Physiology Group, Institute of Neurophysiology, Johannes-Mueller-Center of Physiology, Charité-University Medicine Berlin, Tucholskystrasse 2, 10117 Berlin, Germany. Email: sergei.kirischuk{at}charite.de

At early stages of brain development, GABA plays a dual role. It fulfills important trophic functions and provides a major excitatory drive for the immature neuronal network. Here, we investigated whether GABA itself can limit the strength of excitatory GABAergic synapses on Cajal-Retzius (CR) cells in sagittal slices from the mouse visual cortex. (2S)-3-[[(1S)-1-(3,4-dichlorophenyl)ethyl]amino-2-hydroxypropyl](phenylmethyl)phosphinic acid (CGP55845), a specific GABA_B receptor (GABA_BR) blocker, increased the frequency of spontaneous Ca²⁺ transients and spontaneous and miniature IPSCs (mIPSCs) but did not affect mIPSC amplitudes or kinetics. CGP55845 significantly increased evoked IPSC (eIPSC) amplitudes and decreased the paired-pulse ratio (PPR). Baclofen, a specific GABA_BR agonist, produced opposite effects. The size of the readily releasable pool was not affected by these GABA_BR modulators. The same CGP55845 actions were observed at physiological temperatures, but they were abolished after glutamate decarboxylase block with 3-mercaptopropionic acid (3-MP). These results indicate that presynaptic GABA_BRs dynamically regulate GABA release probability. SNAP-5114, a specific GABA transporter-2/3 (GAT-2/3) blocker, enhanced mIPSC frequencies, decreased PPR, and increased eIPSC amplitudes without changing eIPSC kinetics. These effects were blocked by CGP55845 and 3-MP. NO-711, a specific GAT-1 blocker, prolonged eIPSC decay and decreased eIPSC/mIPSC amplitudes. These NO-711-mediated effects were not sensitive to CGP55845 and 3-MP. We conclude that the strength of GABAergic inputs to CR cells is constrained by GABA_BRs that are persistently activated by ambient GABA. The latter is also provided by GAT-2/3 operating in the reversed mode. Presynaptic GAT-1 functions in the uptake mode and possibly provides GABA for presynaptic vesicle filling.

Key words: presynaptic inhibition; GABA_B receptor; readily releasable pool; release probability; IPSCs; GAT-1; GAT-2/3

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Received Oct. 18, 2005; revised March 16, 2006; accepted March 14, 2006.

Correspondence should be addressed to Dr. Sergei Kirischuk, Sensory and Developmental Physiology Group, Institute of Neurophysiology, Johannes-Mueller-Center of Physiology, Charité-University Medicine Berlin, Tucholskystrasse 2, 10117 Berlin, Germany. Email: sergei.kirischuk{at}charite.de

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