COMPARISON OF RESPONSES OF SPONTANEOUSLY ACTIVE-CELLS IN THE CEREBELLAR PURKINJE LAYER TO PARALLEL FIBER STIMULATION IN SLICE PREPARATIONS AND URETHANE-ANESTHETIZED RATS - EFFECTS OF BENZODIAZEPINE RECEPTOR LIGANDS

1. GABA-mediated inhibitory responses were induced in spontaneously ac tive Purkinje cells by parallel fibre stimulation in cerebellar slices or in urethane anaesthetised rats. Effects of agonist and inverse ago nist benzodiazepine (BDZ) receptor ligands were compared in the prepar ations. 2. Purkinje cells fired simple spikes at higher rates in slice preparations while complex spikes were seldom (in vivo) or never obse rved (slice). Cells fired more regularly in vivo resulting in the occu rrence of rhythmic postinhibitory responses in the PSTH analysis in so me preparations. 3. Single pulse stimulation of parallel fibres at jus t suprathreshold intensity induced inhibition of Purkinje cell activit y in both preparations. At lower firing rates there was a marked incre ase in the duration of this response, which was more evident in vivo w here more slowly firing cells were encountered. 4. BDZ receptor ligand s modified inhibitory responses in slice preparations with only weak e ffects on the firing rates of the cells. These compounds predominately induced changes in firing rate in the anaesthetised rat with little e vidence of direct modification of GABA-mediated synaptic transmission, 5. In a few experiments, following injection of the partial inverse a gonists beta-CCE and beta-CCM, block of the inhibitory response was ob served independent of changes in firing rate. Bidirectional efficacy o f BDZ receptor ligand (agonists decrease firing and increase inhibitor y response, inverse agonists increase firing and decrease inhibitory r esponse) was demonstrated for modulation of inhibitory responses in sl ices and for changes in firing rate in vivo. The increased firing rate response in vivo was biphasic the magnitude of the later phase being correlated with efficacy of inverse agonists. 6. It is concluded that cerebellar slice preparations are more appropriate for studying direct effects of BDZ receptor ligands on GABA-mediated synaptic inhibition than in vivo preparations. (C) 1998 Elsevier Science Inc.