Hyperpolarizing and depolarizing GABAA receptor-mediated dendritic inhibition in area CA1 of the rat hippocampus.
1. gamma-Aminobutyric acidA (GABAA) 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, GABAA and late, GABAB 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 GABAA receptor antagonist bicuculline methiodide (BMI; 30 microM) and were not changed by the GABAB 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 GABAA receptor-mediated population IPSPs (GABAA, fast pIPSPs) and that late field potentials are GABAB receptor-mediated population IPSPs (GABAB, 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 GABAA 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 microM), DNQX and APV long-lasting depolarizing GABAA 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.(ABSTRACT TRUNCATED AT 400 WORDS)
Department of Neurobiology, Northeastern Ohio Universities College of Medicine, Rootstown 44272.
N A
NA
Lambert
A M
AM
Borroni
L M
LM
Grover
T J
TJ
Teyler
D015763:2-Amino-5-phosphonovalerate / Q000494:pharmacology; D000818:Animals; D001640:Bicuculline / Q000031:analogs & derivatives / Q000494:pharmacology; D002712:Chlorides / Q000494:pharmacology; D003712:Dendrites / Q000187:drug effects / Q000502:physiology*; D005071:Evoked Potentials / Q000187:drug effects; D058787:GABA-A Receptor Antagonists; D006624:Hippocampus / Q000502:physiology*; D066298:In Vitro Techniques; D007700:Kinetics; D008433:Mathematics; D008564:Membrane Potentials / Q000187:drug effects; D008959:Models, Neurological; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D009943:Organophosphorus Compounds / Q000494:pharmacology; D011712:Pyramidal Tracts / Q000187:drug effects / Q000502:physiology*; D011810:Quinoxalines / Q000494:pharmacology; D051381:Rats; D011963:Receptors, GABA-A / Q000187:drug effects / Q000502:physiology*; D013569:Synapses / Q000187:drug effects / Q000502:physiology
D002712:Chlorides; D058787:GABA-A Receptor Antagonists; D009943:Organophosphorus Compounds; D011810:Quinoxalines; D011963:Receptors, GABA-A; C017069:bicuculline methiodide; C056723:FG 9041; D015763:2-Amino-5-phosphonovalerate; C066430:CGP 35348; D001640:Bicuculline