In the developing rat hippocampus a tonic GABAA-mediated conductance selectively enhances the glutamatergic drive of principal cells.
In the adult hippocampus, two different forms of GABA(A) receptor-mediated inhibition have been identified: phasic and tonic. The first is due to the activation of GABA(A) receptors facing the presynaptic releasing sites, whereas the second is due to the activation of receptors localized away from the synapses. Because of their high affinity and low desensitization rate, extrasynaptic receptors are persistently able to sense low concentrations of GABA. Here we show that, early in postnatal life, between postnatal day (P) 2 and P6, CA1 and CA3 pyramidal cells but not stratum radiatum interneurons, express a tonic GABA(A)-mediated conductance. Block of the neuronal GABA transporter GAT-1 slightly enhanced the persistent GABA conductance in principal cells but not in GABAergic interneurons. However, in adulthood, a tonic GABA(A)-mediated conductance could be revealed in stratum radiatum interneurons, indicating that the ability of these cells to sense ambient GABA levels is developmentally regulated. Pharmacological analysis of the tonic conductance in principal cells demonstrated the involvement of beta2/beta 3, alpha 5 and gamma 2 GABA(A) receptor subunits. Removal of the tonic depolarizing action of GABA with picrotoxin, reduced the excitability and the glutamatergic drive of principal cells but did not modify the excitability of stratum radiatum interneurons. The increased cell excitability and synaptic activity following the activation of extrasynaptic GABA(A) receptors by ambient GABA would facilitate the induction of giant depolarizing potentials.
Marchionni
Ivan
I
Neuroscience Programme, International School for Advanced Studies, Via Beirut 2-4, 34014 Trieste, Italy.
Omrani
Azar
A
Cherubini
Enrico
E
D000818:Animals; D000831:Animals, Newborn; D004558:Electric Stimulation; D018756:GABA Antagonists / Q000494:pharmacology; D050485:GABA Plasma Membrane Transport Proteins / Q000378:metabolism; D058805:GABA Uptake Inhibitors; D058787:GABA-A Receptor Antagonists; D005973:Glutamine / Q000378:metabolism*; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects / Q000254:growth & development / Q000378:metabolism*; D066298:In Vitro Techniques; D007395:Interneurons / Q000378:metabolism; D008564:Membrane Potentials; D009433:Neural Inhibition / Q000187:drug effects; D009473:Neuronal Plasticity / Q000187:drug effects; D014179:Neurotransmitter Uptake Inhibitors / Q000494:pharmacology; D009557:Nipecotic Acids / Q000494:pharmacology; D010091:Oximes / Q000494:pharmacology; D018408:Patch-Clamp Techniques; D010852:Picrotoxin / Q000494:pharmacology; D017966:Pyramidal Cells / Q000187:drug effects / Q000378:metabolism*; D011724:Pyridazines / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D011963:Receptors, GABA-A / Q000378:metabolism*; D009435:Synaptic Transmission / Q000187:drug effects; D013997:Time Factors; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
D018756:GABA Antagonists; D050485:GABA Plasma Membrane Transport Proteins; D058805:GABA Uptake Inhibitors; D058787:GABA-A Receptor Antagonists; D005973:Glutamine; D014179:Neurotransmitter Uptake Inhibitors; D009557:Nipecotic Acids; D010091:Oximes; D010852:Picrotoxin; D011724:Pyridazines; D011963:Receptors, GABA-A; D005680:gamma-Aminobutyric Acid; C511535:Gabra5 protein, rat; C502185:Gabrb2 protein, rat; C546276:Gabrb3 protein, rat; C493415:Slc6a1 protein, rat; C078793:NNC 711; C049853:gabazine