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Research ArticleArticle

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

Yukun Yuan and William D. Atchison
Journal of Pharmacology and Experimental Therapeutics March 1999, 288 (3) 1015-1025;
Yukun Yuan
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William D. Atchison
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Abstract

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.

Footnotes

  • Send reprint requests to: Address all correspondence including reprint requests to: Dr. William D. Atchison, Ph.D., Michigan State University, Department of Pharmacology and Toxicology, B-331 Life Sciences Building, East Lansing, Michigan 48824-1317. E-mail:atchisol{at}pilot.msu.edu

  • ↵1 This study was supported by National Institutes of Health Grant R01ES03299. Portions of this work were presented at the 1997 and 1998 Annual Meetings of the Society of Toxicology in Cincinnati, Ohio and Seattle, Washington, respectively, and were published as abstracts in The Toxicologist,36:13, 1997 and The Toxicologist,37:195, 1998.

  • ↵2 This paper was submitted (Y.Y.) in partial completion of the requirements of the Ph.D. degree in Pharmacology and Toxicology at Michigan State University. Current address: Department of Opthalmology, University of Michigan, Ann Arbor, MI.

  • Abbreviations:
    ACSF
    artificial cerebrospinal fluid
    [Ca++]i
    intracellular concentration of Ca++
    CFRs
    climbing-fiber responses
    CF-EPSPs
    climbing-fiber excitatory postsynaptic potentials
    DNQX
    6,7-dinitroquinoxaline-2,3-dione
    MeHg
    methylmercury
    PFVs
    parallel-fiber volleys
    PSRs
    postsynaptic responses
    PF-EPSPs
    parallel-fiber excitatory postsynaptic potentials
    TTX
    tetrodotoxin
    • Received May 14, 1998.
    • Accepted October 7, 1998.
  • The American Society for Pharmacology and Experimental Therapeutics
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Journal of Pharmacology and Experimental Therapeutics: 288 (3)
Journal of Pharmacology and Experimental Therapeutics
Vol. 288, Issue 3
1 Mar 1999
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Research ArticleArticle

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

Yukun Yuan and William D. Atchison
Journal of Pharmacology and Experimental Therapeutics March 1, 1999, 288 (3) 1015-1025;

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Research ArticleArticle

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

Yukun Yuan and William D. Atchison
Journal of Pharmacology and Experimental Therapeutics March 1, 1999, 288 (3) 1015-1025;
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