Baclofen reduces post‐synaptic potentials of rat cortical neurones by an action other than its hyperpolarizing action.

Abstract

1. Intracellular recordings were obtained from neurones in layers 2 and 3 of the rat frontal neocortex in an in vitro slice preparation. Three distinct types of stimulation-evoked post-synaptic potentials were recorded in these neurones: excitatory post-synaptic potentials (e.p.s.p.s.): bicuculline-sensitive, chloride-dependent inhibitory post-synaptic potentials (i.p.s.p.s.) with times to peak of 20-25 ms (fast(f)-i.p.s.p.s.): bicuculline-insensitive, potassium-dependent i.p.s.p.s. with times to peak of 150-250 ms (long(l)-i.p.s.p.s.). 2. The effects of baclofen were investigated on seventy-one neurones. Baclofen was applied by ionophoresis or pressure ejection from micropipettes or was added to the superfusion medium. 3. Baclofen depressed stimulation-evoked e.p.s.p.s. in fifty-seven of the sixty neurones tested. This effect was associated with an increase in the stimulation intensity required to produce a synaptically evoked action potential for thirty-nine of forty-four neurones. 4. Baclofen depressed f-i.p.s.p.s. in thirty-seven of the thirty-nine neurones tested and l-i.p.s.p.s. in each one of the seventeen neurones tested. Reversal potential values for each type of i.p.s.p. were not changed by baclofen and its depressions of each were independent of membrane potential (Em). Baclofen reduced the magnitude and the duration of the conductance increases that were associated with f- and l-i.p.s.p. 5. Baclofen hyperpolarized forty of seventy-one neurones and produced outward currents in three of four neurones recorded in voltage clamp at holding potentials between -55 and -65 mV. These actions were associated with 10-58% reductions of neuronal input resistance (RN) and 10-20% increases in neuronal input conductance (gN), respectively. Baclofen decreased the direct excitability of twenty-three of twenty-seven neurones tested. Determinations of the reversal potential for baclofen-induced changes of Em indicate that baclofen increases the conductance of rat neocortical neurones to potassium ions. 6. The EC50 for each action of DL-baclofen was approximately 1 .mu.M. L-Baclofen was > 100 times more potent than D-baclofen. 7. Concentrations of bicuculline that blocked f-i.p.s.p.s. and responses to ionophoretically applied .gamma.-aminobutyric acid (GABA) had no effect on the depressions of e.p.s.p.s. or the hyperpolarizations and decreases in RN that baclofen produced. 8. Baclofen did not reduce the duration of action potentials that were prolonged with intracellular injections of caesium ions or by superfusions with medium that contained 10-mM-tetraethylammonium (TEA). 9. Almost complete depressions of post-synaptic potentials were observed for some neurones on which baclofen produced no hyperpolarization or apparent decrease in RN. Baclofen''s depressions of post-synaptic potentials outlasted the hyperpolarizations and the decreases in RN and direct excitability that baclofen produced, often by several minutes. Applications of baclofen that produced almost complete depressions of post-synaptic potentials did not significantly reduce depolarizations produced by L-glutamate, L-asparate, N-methyl-D-aspartate (NMDA), or GABA. At the same time that baclofen decreased resting RN, conductance increases during stimulation-evoked i.p.s.p.s. were reduced by baclofen. These results indicate that baclofen depresses post-synaptic potentials evoked in rat neocortical neurones by an action that is additional to and separate from its action to increase post-synaptic potassium conductance.