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

Abstract

CGP55845 significantly increased evoked IPSC (eIPSC) amplitudes and decreased the paired-pulse ratio (PPR).Baclofen, a specific GABA B R agonist, produced opposite effects. The size of the readily releasable pool was not affected by these GABA B R 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 B Rs 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 B Rs 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.

The Mammalian Interaural Time Difference Detection Circuit Is Differentially Controlled by GABAB Receptors during Development

“…Furthermore, GABA B Rs have been implicated both in the regulation of circuit formation during development (Behar et al, 2000;Represa and Ben-Ari, 2005) and in the acute modulation of network properties in the mature animal (Scanziani, 2000;Magnusson et al, 2008;Oswald et al, 2009;Pan et al, 2009). Consistent with our data, anatomical and physiological studies in other brain structures suggest that presynaptic GABA B Rs are present and functional on excitatory and inhibitory inputs during early development and in adult animals (Gaiarsa et al, 1995;Varela et al, 1997;Ló pez-Bendito et al, 2002;Kirmse and Kirischuk, 2006). However, there is little information on changes in GABA B R function during development.…”

Ethanol Consumption during Early Pregnancy Alters the Disposition of Tangentially Migrating GABAergic Interneurons in the Fetal Cortex

“…In many brain regions examined to date, ambient levels of GABA and/or glutamate have been demonstrated and implicated in maintaining a baseline level of activity that regulates neuronal excitability and circuit function (Ge et al, 2006;Kirmse and Kirischuk, 2006;Herman and Jahr, 2007;LeMeur et al, 2007). With specific regard to GABA, the prevailing thought is that synaptic spillover results in the ambient extracellular accumulation of GABA, which tonically activates high-affinity, slowly desensitizing extra-synaptic GABA A receptor isoforms with cell-type specific pharmacological prop- erties (Nusser and Mody, 2002;Fritschy and Brunig, 2003;Caraiscos et al, 2004).…”

Presynaptic GABABReceptors Regulate Experience-Dependent Development of Inhibitory Short-Term Plasticity

“…In paired-pulse studies, GABA released from the first pulse activates GABA B autoreceptors, which inhibit release on the subsequent pulse. Therefore, these receptors are associated with STP at various inhibitory synapses (Deisz and Prince, 1989;Davies and Collingridge, 1993;Fukuda et al, 1993;Mott et al, 1993;Pearce et al, 1995;Poncer et al, 2000;Kirmse and Kirischuk, 2006). Despite the primacy of GABA B receptors to synaptic transmission, it is unknown whether their development depends on experience.…”