Vol. 288, Issue 3, 1015-1025, March 1999

Comparative Effects of Methylmercury on Parallel-Fiber and Climbing-Fiber Responses of Rat Cerebellar Slices¹

Yukun Yuan² and William D. Atchison

Department of Pharmacology and Toxicology, Neuroscience Program and Institute for Environmental Toxicology, Michigan State University, East Lansing, Michigan

The environmental neurotoxicant methylmercury (MeHg) causes profound disruption of cerebellar function. Previous studies have shown that acute exposure to MeHg impairs synaptic transmission in both the peripheral and central nervous systems. However, the effects of MeHg on cerebellar synaptic function have never been examined. In the present study, effects of acute exposure to MeHg on synaptic transmission between parallel fibers or climbing fibers and Purkinje cells were compared in 300- to 350-µm cerebellar slices by using extracellular and intracellular microelectrode-recording techniques. Field potentials of parallel-fiber volleys (PFVs) and the associated postsynaptic responses (PSRs) were recorded in the molecular layer by stimulating the parallel fibers in transverse cerebellar slices. The climbing-fiber responses were also recorded in the molecular layer by stimulating white matter in sagittal cerebellar slices. At 20, 100, and 500 µM, MeHg reduced the amplitude of both PFVs and the associated PSRs to complete block, however, it blocked PSRs more rapidly than PFVs. MeHg also decreased the amplitudes of climbing-fiber responses to complete block. For all responses, an initial increase in amplitude preceded MeHg-induced suppression. Intracellular recordings of excitatory postsynaptic potentials of Purkinje cells were compared before and after MeHg. At 100 µM and 20 µM, MeHg blocked the Na⁺-dependent, fast somatic spikes and Ca⁺⁺-dependent, slow dendritic spike bursts. MeHg also hyperpolarized and then depolarized Purkinje cell membranes, suppressed current conduction from parallel fibers or climbing fibers to dendrites of Purkinje cells, and blocked synaptically activated local responses. MeHg switched the pattern of repetitive firing of Purkinje cells generated 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 exposure to MeHg causes a complex pattern of effects on cerebellar synaptic transmission, with apparent actions on both neuronal excitability and chemical synaptic transmission.