PRESYNAPTIC GABA(B) RECEPTORS MODULATE IPSPS EVOKED IN NEURONS OF DEEP CEREBELLAR NUCLEI IN-VITRO

1. Recording from deep cerebellar nuclei neurons, we investigated the role of presynaptic gamma-aminobutyric acid-B (GABA(B)) receptors in t he modulation of monosynaptic inhibitory postsynaptic potentials (IPSP s) evoked by stimulation of Purkinje cells in rat slice cultures. 2. B ath application of the GABA(B) receptor agonist, baclofen (10 and 100 mu M) induced two effects in cerebellar nuclei neurons: a postsynaptic hyperpolarization of 4.2 +/- 1.7 (SD) mV and a reduction in the ampli tude of evoked IPSPs (30 +/- 10%). 3. When the postsynaptic GABA(B) re sponse was blocked by filling the electrode with cesium methanesulfona te (2 M), or with a solution containing QX 314 (50 mM), bath applicati on of baclofen (10 mu M) reversibly depressed the evoked IPSPs by 36.7 +/- 18.7% and 42 +/- 20.3%, respectively. Under these experimental co nditions, baclofen (10 mu M) also reduced the amplitude of spontaneous IPSPs (10.2 +/- 9.5%) and decreased their frequency by 45.6 +/- 8.8%, suggesting a presynaptic site of action. 4. The presynaptic action of baclofen was not due to activation of receptors on the somata of Purk inje cells: baclofen (100 mu M) failed to alter membrane holding curre nt in Purkinje cells, and it had no effect on the rate of spontaneous action-potential discharge in Purkinje cells in the presence of ionotr opic glutamate receptor antagonists (6-cyano-7-nitroquinoxaline-2,3-di one, 20 mu M; D-2-amino-5-phosphonovalerate, 40 mu M). 5. IPSPs could be evoked by extracellular stimulation of the Purkinje cell layer or b y direct stimulation of the fiber bundle connecting Purkinje cells to deep cerebellar neurons. In both situations, baclofen (10 mu M) reduce d the amplitude of evoked IPSPs by 32.7 +/- 8.8% and 31.2 +/- 10.2%, r espectively. 6. These results demonstrate that GABA(B) receptors are p resent on the terminals of Purkinje cells. Their activation causes a d ecrease in the amplitude of evoked IPSPs recorded in deep cerebellar n uclei and also reduces the frequency of spontaneous inhibitory events.