Comparative effects of methylmercury on parallel-fiber and climbing-fiber responses of rat cerebellar slices

The environmental neurotoxicant methylmercury (MeHg) causes profound disrup tion of cerebellar function. Previous studies have shown that acute exposur e to MeHg impairs synaptic transmission in both the peripheral and central nervous systems. However, the effects of MeHg on cerebellar synaptic functi on have never been examined. In the present study, effects of acute exposur e to MeHg on synaptic transmission between parallel fibers or climbing fibe rs and Purkinje cells were compared in 300- to 350-mu m cerebellar slices b y using extracellular and intracellular microelectrode-recording techniques . Field potentials of parallel-fiber volleys (PFVs) and the associated post synaptic responses (PSRs) were recorded in the molecular layer by stimulati ng the parallel fibers in transverse cerebellar slices. The climbing-fiber responses were also recorded in the molecular layer by stimulating white ma tter in sagittal cerebellar slices. At 20, 100, and 500 mu M, MeHg reduced the amplitude of both PFVs and the associated PSRs to complete block, howev er, it blocked PSRs more rapidly than PFVs. MeHg also decreased the amplitu des of climbing-fiber responses to complete block. For all responses, an in itial increase in amplitude preceded MeHg-induced suppression. Intracellula r recordings of excitatory postsynaptic potentials of Purkinje cells were c ompared before and after MeHg. At 100 mu M and 20 mu M, MeHg blocked the Na +-dependent, fast somatic spikes and Ca++-dependent, slow dendritic spike b ursts. MeHg also hyperpolarized and then depolarized Purkinje cell membrane s, suppressed current conduction from parallel fibers or climbing fibers to dendrites of Purkinje cells, and blocked synaptically activated local resp onses. MeHg switched the pattern of repetitive firing of Purkinje cells gen erated spontaneously or by depolarizing current injection at Purkinje cell soma from predominantly Na+ dependent, fast somatic spikes to predominantly Ca++-dependent, low amplitude, slow dendritic spike bursts. Thus, acute ex posure to MeHg causes a complex pattern of effects on cerebellar synaptic t ransmission, with apparent actions on both neuronal excitability and chemic al synaptic transmission.