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 p ossible functional heterogeneity of inhibitory synapses between differ ent interneurons and CA1 pyramidal cells. 2. We therefore compared inh ibitory postsynaptic potentials (IPSPs) and currents (IPSCs) in CA1 py ramidal cells, which were evoked from two stimulation sites (stratum o riens and stratum radiatum). Stimulation in stratum oriens yielded fas ter 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 bloc ker. However, the effect of tiagabine was significantly more pronounce d following stimulation in stratum radiatum than in stratum oriens (pr olongation of IPSC half-decay time by 167 vs. 115%, respectively). 4. In situ hybridization with antisense mRNA for the GABA-synthesizing en zyme glutamate decarboxylase (GAD65/67) and the GABA transporter GAT-1 . showed that the proportion of interneurons expressing GAT-1 was lowe r in stratum oriens than in stratum radiatum/lacunosum-moleculare. 5. From these functional and molecular data we conclude that the regulati on of IPSP and IPSC kinetics in CA1 pyramidal cells by neuronal GABA u ptake differs between layers. Our findings suggest that this laminar d ifference is caused by a lower expression of GAT-1 in interneurons in stratum oriens than in stratum radiatum/lacunosum-moleculare