Phaclofen inhibition of the slow inhibitory postsynaptic potential in hippocampal slice cultures: a possible role for the GABAB-mediated inhibitory postsynaptic potential.
The GABAA antagonist bicuculline methiodide and the GABAB antagonist phaclofen were used to examine the function of the fast inhibitory postsynaptic potential and slow inhibitory postsynaptic potential, in hippocampal slice cultures in the rat. These cultures form easily-visualized monolayers of nerve cells which maintain the structure and synaptic organization of transverse hippocampal slices. The present study shows that the cellular and synaptic physiological properties of slice cultures are very similar, but not identical, to those observed in acutely-prepared hippocampal slices. The major difference is a higher incidence of fast excitatory postsynaptic potentials and inhibitory postsynaptic potentials compared to slices, and the appearance of spontaneous slow inhibitory postsynaptic potentials. This increase in synaptic drive has been useful for our investigation of the role of GABA-mediated inhibitory postsynaptic potentials. Bath application of 10 microM bicuculline blocked the fast inhibitory postsynaptic potentials and gave rise to bursts 1-11 s in duration. The presence of the slow inhibitory postsynaptic potentials did not prevent bicuculline-induced burst activity. Phaclofen (1 mM) perfused in the bath reversibly blocked the slow inhibitory postsynaptic potential, but did not result in the formation of large paroxysmal depolarizing shift-like bursts as seen with bicuculline. Rather, block of the slow inhibitory postsynaptic potential resulted in the formation of repetitive "afterdischarge bursts". These afterdischarge potentials typically appeared with a delay of 2-15 min following block of the slow inhibitory postsynaptic potential, during which time there was a gradual increase in non-synchronized excitatory activity. Once established, this cycle of increasing excitatory activity culminating in afterdischarge potentials recurred at 2-4 min intervals while phaclofen was present.(ABSTRACT TRUNCATED AT 250 WORDS)
Malouf
A T
AT
Department of Neurological Surgery, University of Washington, Seattle 98195.
Robbins
C A
CA
Schwartzkroin
P A
PA
D000200:Action Potentials; D000818:Animals; D001418:Baclofen / Q000031:analogs & derivatives* / Q000494:pharmacology; D001640:Bicuculline / Q000494:pharmacology; D018756:GABA Antagonists; D006624:Hippocampus / Q000187:drug effects / Q000502:physiology*; D009433:Neural Inhibition / Q000187:drug effects*; D009924:Organ Culture Techniques; D051381:Rats; D005680:gamma-Aminobutyric Acid / Q000502:physiology*
D018756:GABA Antagonists; C052329:phaclofen; D005680:gamma-Aminobutyric Acid; D001418:Baclofen; D001640:Bicuculline