FREQUENCY-DEPENDENT ACTIVATION OF A SLOW N-METHYL-D-ASPARTATE-DEPENDENT EXCITATORY POSTSYNAPTIC POTENTIAL IN TURTLE CEREBELLUM BY MOSSY FIBER AFFERENTS

The synaptic responses of turtle cerebellar Purkinje cells to stimulat ion of localized messy fibre systems have been studied by use of intra somatic and intradendritic recordings in a brainstem-cerebellum prepar ation in vitro. Activation of messy fibre inputs from the spinocerebel lar pathway evoked fast, disynaptic postsynaptic potentials which were graded in amplitude with stimulus intensity and elicited at latencies consistent with those reported for peripheral nerve stimulation. Repe titive activation (50-100 Hz, 2-10 stimuli) of both spinocerebellar an d trigeminocerebellar pathways evoked a slow, long-lasting excitatory postsynaptic potential regardless of whether single stimuli resulted i n excitatory, inhibitory, or no postsynaptic responses. This slow pote ntial was capable of triggering dendritic pacemaker discharges in reco rded Purkinje cells in addition to volleys of simple spikes when activ ated at or near resting membrane potential. The fast excitatory synapt ic potentials evoked by spinocerebellar stimulation were blocked by th e glutamate receptor antagonist 6-cyano-7-nitroquinoxaline-2,3-dione, consistent with the hypothesis that they are mediated by activation of ionotropic glutamate receptors of the pha-amino-3-hydroxy-5-methyliso xazole-4-proprionic acid subtype at the messy fibre-granule cell synap se and the subsequent parallel fibre-Purkinje cell synapse. The slow e xcitatory synaptic potential evoked by repetitive stimulation of eithe r the spinocerebellar tract or trigeminal nerve was blocked by DL-2-am ino-5-phosphonvalerate, indicating that this potential is primarily de pendent upon N-methyl-D-aspartate receptors at the messy fibre-granule cell synapse for its expression. This slow potential was reversibly p otentiated by L-2-amino-4-phosphonobutyrate and bicuculline; the metab otropic glutamate antagonist(+)-alpha-methyl-4-carboxyphenylglycine di d not block this potentiation. The ability of messy fibre inputs to dr ive long, slow excitatory events in Purkinje cells adds another dimens ion to the mechanisms by which various sensory modalities can be proce ssed interactively in the cerebellar cortex. The ability of incoming s ystems to access a second, longer duration response of the cerebellar output neuron may be of significant consequence to our understanding o f the manner in which this neural centre integrates sensory informatio n from multiple sources.