Laminar difference in GABA uptake and GAT-1 expression in rat CA1.
1. The axonal plexus of most hippocampal interneurons is restricted to certain strata within the target region. This lamination suggests a possible functional heterogeneity of inhibitory synapses between different interneurons and CA1 pyramidal cells. 2. We therefore compared inhibitory postsynaptic potentials (IPSPs) and currents (IPSCs) in CA1 pyramidal cells, which were evoked from two stimulation sites (stratum oriens and stratum radiatum). Stimulation in stratum oriens yielded faster decaying IPSPs and IPSCs than stimulation in stratum radiatum. 3. IPSP and IPSC kinetics were regulated by GABA uptake in both layers as indicated by the prolongation of the signals under tiagabine, a GAT-1 (neuronal GABA plasma membrane transporter)-specific GABA-uptake blocker. However, the effect of tiagabine was significantly more pronounced following stimulation in stratum radiatum than in stratum oriens (prolongation of IPSC half-decay time by 167 vs. 115 %, respectively). 4. In situ hybridization with antisense mRNA for the GABA-synthesizing enzyme glutamate decarboxylase (GAD65/67) and the GABA transporter GAT-1 showed that the proportion of interneurons expressing GAT-1 was lower in stratum oriens than in stratum radiatum/lacunosum-moleculare. 5. From these functional and molecular data we conclude that the regulation of IPSP and IPSC kinetics in CA1 pyramidal cells by neuronal GABA uptake differs between layers. Our findings suggest that this laminar difference is caused by a lower expression of GAT-1 in interneurons in stratum oriens than in stratum radiatum/lacunosum-moleculare.
Institut fur Physiologie der Charite, Humboldt-Universitat, Tucholskystrasse 2, 10117 Berlin, Germany. engeldo@comcom.rz.charite.hu-berline.de
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Engel
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Schmitz
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Gloveli
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Frahm
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Heinemann
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Draguhn
D000818:Animals; D001369:Axons / Q000378:metabolism / Q000502:physiology; D002352:Carrier Proteins / Q000096:biosynthesis*; D004558:Electric Stimulation; D019706:Excitatory Postsynaptic Potentials / Q000502:physiology; D018756:GABA Antagonists / Q000494:pharmacology; D050485:GABA Plasma Membrane Transport Proteins; D005968:Glutamate Decarboxylase / Q000378:metabolism; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism*; D017403:In Situ Hybridization; D007395:Interneurons / Q000201:enzymology; D007700:Kinetics; D008565:Membrane Proteins / Q000096:biosynthesis*; D026901:Membrane Transport Proteins; D009557:Nipecotic Acids / Q000494:pharmacology; D027361:Organic Anion Transporters; D017966:Pyramidal Cells / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D000078308:Tiagabine; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
D002352:Carrier Proteins; D018756:GABA Antagonists; D050485:GABA Plasma Membrane Transport Proteins; D008565:Membrane Proteins; D026901:Membrane Transport Proteins; D009557:Nipecotic Acids; D027361:Organic Anion Transporters; C493415:Slc6a1 protein, rat; D005680:gamma-Aminobutyric Acid; D005968:Glutamate Decarboxylase; D000078308:Tiagabine