Effects of baclofen and bicuculline on inhibition in the fascia dentata and hippocampus regio superior.
The effects of microiontophoretically applied baclofen, bicuculline and phaclofen were studied on evoked field responses, paired-pulse (PP) plasticity and single-unit activity of dentate granule cells (DGCs) and CA1 pyramidal cells (PCs) in anesthetized rats. The GABAB agonist, baclofen, increased population spike (PS) amplitudes in the dentate evoked by perforant path stimulation but decreased PS amplitudes in CA1 evoked by Schaffer collateral stimulation, whereas the GABAA antagonist, bicuculline, increased PS amplitudes in both regions. Neither baclofen nor bicuculline had significant effects on dendritically recorded population excitatory postsynaptic potentials (EPSPs) in the dentate or CA1 evoked by stimulation of their respective afferents. Control PP curves in the dentate revealed a triphasic response of inhibition/potentiation/inhibition, whereas control PP curves in CA1 manifested a biphasic response of inhibition/potentiation of test/conditioned PS amplitudes. Baclofen and bicuculline reversed the early and late phases of PP inhibition in the dentate and the early phase of PP inhibition in CA1. The GABAB antagonist, phaclofen, selectively reversed the effects of baclofen on PP inhibition in both the dentate and CA1. Whereas baclofen had no effect, bicuculline incre sed and phaclofen decreased DGC single-unit spontaneous firing rate, while baclofen decreased and bicuculline and phaclofen increased PC firing rate. These results support and extend studies suggesting that GABAergic feedback inhibition of DGCs and PCs is mediated by postsynaptic GABAA receptors and feedback inhibition of PCs is mediated by postsynaptic GABAB receptors. Our results also provide significant new evidence suggesting that postsynaptic inhibition in the dentate is not regulated by GABAB receptors and that feedback and feedforward inhibition of DGCs and PCs is regulated by presynaptic GABAB receptors located on GABAergic interneurons.
Steffensen
S C
SC
Department of Neuropharmacology, Research Institute of Scripps Clinic, La Jolla, CA 92037.
Henriksen
S J
SJ
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D001418:Baclofen / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000494:pharmacology*; D001640:Bicuculline / Q000008:administration & dosage / Q000494:pharmacology*; D004558:Electric Stimulation / Q000379:methods; D005071:Evoked Potentials / Q000187:drug effects; D006624:Hippocampus / Q000187:drug effects / Q000502:physiology*; D007395:Interneurons / Q000187:drug effects / Q000502:physiology; D007478:Iontophoresis; D008297:Male; D011712:Pyramidal Tracts / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D011919:Rats, Inbred Strains; D011963:Receptors, GABA-A / Q000187:drug effects / Q000502:physiology; D013569:Synapses / Q000187:drug effects / Q000502:physiology
D011963:Receptors, GABA-A; C052329:phaclofen; D001418:Baclofen; D001640:Bicuculline