MUSCIMOL-INDUCED LONG-TERM DEPRESSION IN THE HIPPOCAMPUS - LACK OF DEPENDENCE ON EXTRACELLULAR CALCIUM

We have recently reported a new protocol for inducing long-term depres sion through activation of GABA, receptors in the hippocampal slice. T his long-term depression is reversed by bicuculline and potentiated by neurosteroids such as alphaxalone and 5 alpha-pregnan-3 alpha-ol-20-o ne. It was also shown that glutamate receptor activity is not involved in the induction of this type of long-term depression. The present st udy investigates the role of calcium in the induction of this novel fo rm of long-term depression and attempts to determine the mechanism of reversal of muscimol-induced long-term depression. Extracellular recor dings were made in the CAI pyramidal cell layer of rat hippocampal sli ces following orthodromic stimulation of Schaffer collateral fibres in stratum radiatum (0.01 Hz). It was observed that the muscimol-induced long-term depression can be obtained in the absence of calcium in the bathing medium. In addition to this, the long-term depression was rev ersed by N-methyl-D-aspartate, kainic acid, high potassium medium, ver atrine and the calcium ionophore A23187 but not high calcium (10 mM) m edium. High potassium medium in the absence of calcium reversed the lo ng-term depression induced by muscimol 10 mu M. The results suggest th at this type of glutamate-independent long-term depression can be indu ced in the absence of extracellular calcium. Extracellular calcium is not necessary for reversal of the long-term depression, although when intracellular calcium levels are raised, as by A23187, this is capable of inducing reversal.