Hyperpolarizing and depolarizing GABA(A) receptor-mediated dendritic inhibition in area CA1 of the rat hippocampus

1. γ-Aminobutyric acid(A) (GABA(A)) receptor-mediated inhibition of pyramidal neuron dendrites was studied in area CA1 of the rat hippocampal slice preparation with the use of intracellular and extracellular recording and one-dimensional current source-density (CSD) analysis. 2. Electrical stimulation of Schaffer collateral/commissural fibers evoked monosynaptic excitatory postsynaptic potentials (EPSPs) and population EPSPs, which were followed by biphasic inhibitory postsynaptic potentials (IPSPs). In the presence of the excitatory amino acid receptor antagonists 6,7- dinitroquinoxaline-2,3-dione (DNQX) and D,L-2-amino-5-phosphonovalerate (APV), stimulation in stratum radiatum evoked monosynaptic fast, GABA(A) and late, GABA(B) receptor-mediated IPSPs and fast and late positive field potentials recorded in s. radiatum. 3. Fast monosynaptic IPSPs and fast positive field potentials evoked in the presence of DNQX and APV were reversibly abolished by the GABA(A) receptor antagonist bicuculline methiodide (BMI; 30 μM) and were not changed by the GABA(B) receptor antagonist P-[3-aminopropyl]-P-diethoxymethylphosphinic acid (CGP 35 348; 0.1-1.0 mM). CGP 35 348 (0.1 mM) reversibly blocked late monosynaptic IPSPs and late positive field potentials. These results suggest that fast field potentials are GABA(A) receptor-mediated population IPSPs (GABA(A), fast pIPSPs) and that late field potentials are GABA(B) receptor-mediated population IPSPs (GABA(B), late pIPSPs). 4. Fast pIPSPs were reversibly abolished when the extracellular Cl^- concentration ([Cl^-](o)) was reduced from 132 to 26 mM in parallel with a depolarizing shift in the reversal potential of fast IPSPs. Paired or repetitive stimulation in s. radiatum reversibly depressed fast pIPSPs and fast IPSPs. Paired-pulse depression of fast pIPSPs was reversibly antagonized by CGP 35 348 (0.4-0.8 mM). 5. Laminar analysis of s. radiatum-evoked fast pIPSPs and one-dimensional CSD analysis revealed active current sources in s. radiatum and passive current sinks in s. oriens and s. lacunosum moleculare. S. radiatum sources were abolished by pressure application of BMI in s. radiatum but not in s. oriens. Stimulation in s. oriens, s. pyramidale, or s. lacunosum moleculare evoked GABA(A) current sources horizontal to the stimulation site. Changes in the dendritic location of inhibitory current with changes in stimulus location paralleled changes in the distribution of excitatory current. 6. In the presence of 4- aminopyridine (50-100 μM), DNQX and APV long-lasting depolarizing GABA(A) receptor-mediated responses (LLDs) occurred spontaneously or could be evoked. Current sinks associated with s. radiatum-evoked LLDs were located in the same dendritic area as sources associated with hyperpolarizing fast IPSPs. 7. These results suggest that activation of GABA(A) receptors located on pyramidal neuron apical and basal dendrites produces outward Cl^-1 current and hyperpolarizing IPSPs. This suggests that depolarizing responses to dendritic GABA application and orthodromic activation in area CA1 do not result from inward chloride current.