title: Frequency dependent activation of a slow N-methyl-D-aspartate-dependent excitatory postsynaptic potential in turtle cerebellum by mossy fibre afferents.
abstract: The synaptic responses of turtle cerebellar Purkinje cells to stimulation of localized mossy fibre systems have been studied by use of intrasomatic and intradendritic recordings in a brainstem-cerebellum preparation in vitro. Activation of mossy fibre inputs from the spinocerebellar 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. Repetitive activation (50-100 Hz, 2-10 stimuli) of both spinocerebellar and trigeminocerebellar pathways evoked a slow, long-lasting excitatory postsynaptic potential regardless of whether single stimuli resulted in excitatory, inhibitory, or no postsynaptic responses. This slow potential was capable of triggering dendritic pacemaker discharges in recorded Purkinje cells in addition to volleys of simple spikes when activated at or near resting membrane potential. The fast excitatory synaptic potentials evoked by spinocerebellar stimulation were blocked by the 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 alpha-amino-3-hydroxy-5-methylisox-azole-4-proprionic acid subtype at the mossy fibre-granule cell synapse and the subsequent parallel fibre-Purkinje cell synapse. The slow excitatory synaptic potential evoked by repetitive stimulation of either the spinocerebellar tract or trigeminal nerve was blocked by DL-2-amino-5-phosphonvalerate, indicating that this potential is primarily dependent upon N-methyl-D-aspartate receptors at the mossy fibre-granule cell synapse for its expression. This slow potential was reversibly potentiated by L-2-amino-4-phosphonobutyrate and bicuculline; the metabotropic glutamate antagonist (+)-alpha-methyl-4-carboxyphenylglycine did not block this potentiation. The ability of mossy fibre inputs to drive long, slow excitatory events in Purkinje cells adds another dimension to the mechanisms by which various sensory modalities can be processed interactively in the cerebellar cortex. The ability of incoming systems to access a second, longer duration response of the cerebellar output neuron may be of significant consequence to our understanding of the manner in which this neural centre integrates sensory information from multiple sources.
authors.affiliation: Department of Neuroscience and Anatomy, Pennsylvania State University College of Medicine, M.S. Hershey Medical Center, Hershey 17033, USA.
authors.forename: L J
authors.initials: LJ
authors.lastname: Larson-Prior
authors.forename: P D
authors.initials: PD
authors.lastname: Morrison
authors.forename: R M
authors.initials: RM
authors.lastname: Bushey
authors.forename: N T
authors.initials: NT
authors.lastname: Slater
mesh_terms: D015763:2-Amino-5-phosphonovalerate / Q000494:pharmacology; D018750:6-Cyano-7-nitroquinoxaline-2,3-dione / Q000494:pharmacology; D000344:Afferent Pathways / Q000187:drug effects*; D000818:Animals; D001640:Bicuculline / Q000494:pharmacology; D002531:Cerebellum / Q000187:drug effects*; D004558:Electric Stimulation; D005071:Evoked Potentials / Q000187:drug effects; D016202:N-Methylaspartate / Q000494:pharmacology*; D017729:Presynaptic Terminals / Q000187:drug effects*; D011689:Purkinje Cells / Q000187:drug effects; D014426:Turtles
chemical_list: D016202:N-Methylaspartate; D018750:6-Cyano-7-nitroquinoxaline-2,3-dione; D015763:2-Amino-5-phosphonovalerate; D001640:Bicuculline