Disruption by methylmercury of membrane excitability and synaptic transmission of CA1 neurons in hippocampal slices of the rat.
In order to examine the effects of methylmercury (MeHg) on central synaptic transmission, field potentials were recorded in the CA1 neurons of hippocampal slices by using extracellular microelectrode recording techniques. After stimulation of Schaffer collaterals at low frequency (0.25 Hz), population spikes and excitatory postsynaptic potentials (EPSPs) were recorded at the cell bodies and apical dendrites of CA1 pyramidal cells, respectively. Antidromically activated population spikes were also recorded at the cell bodies of CA1 pyramidal cells by stimulating the alveus. Long-term potentiation (LTP) was induced by application of brief high-frequency stimulation (15 trains of four stimuli per train at 100 Hz) after 25 min of population spike baseline recordings. MeHg was applied to slices acutely by bath perfusion with artificial cerebrospinal fluid (ACSF). At 20-500 microM, MeHg significantly increased and then decreased the amplitudes of, or blocked, the population spikes, EPSPs, and antidromically activated population spikes. Time to increase and time to block of these field potentials were concentration-dependent. Exposure of slices to 4 microM MeHg for 180 min increased but did not reduce the amplitudes of population spikes, EPSPs, or antidromically activated population spikes. The effects of MeHg on population spikes induced by either orthodromic or antidromic stimulation were similar. In the absence of MeHg, application of high-frequency stimulation increased population spike amplitudes by 60-100%. This effect (LTP) could be sustained for more than 2 hr in the absence of MeHg. When 100 microM MeHg was applied concomitantly with high-frequency stimulation, the population spike amplitudes were increased by an additional 20-50% based on the already elevated population spike amplitude by high-frequency stimulation. Subsequently, population spike amplitudes were reduced and finally blocked in a manner similar to the effect of MeHg on population spikes recorded without high-frequency stimulation. Application of MeHg (100 microM) for 20 min prior to high-frequency stimulation did not prevent induction of LTP even though the population spike amplitudes had been decreased by more than 10% of the control level, suggesting that MeHg may not alter induction of LTP. Reversibility of the effects of MeHg was examined by washing slices with MeHg-free ACSF or 1 mM D-penicillamine for 60-120 min after MeHg treatment. Washing slices with MeHg-free ACSF caused at best partial reversal of effects of MeHg. D-Penicillamine, a chelator of MeHg, completely reversed the effects of MeHg on EPSPs but only partially reversed the effects of MeHg on population spikes, antidromically activated population spikes, and LTP.(ABSTRACT TRUNCATED AT 400 WORDS)
Yuan
Y
Y
Department of Pharmacology and Toxicology, Michigan State University, East Lansing 48824-1317.
Atchison
W D
WD
D000818:Animals; D004558:Electric Stimulation; D006624:Hippocampus / Q000187:drug effects* / Q000502:physiology; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D008767:Methylmercury Compounds / Q000494:pharmacology*; D010396:Penicillamine / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013569:Synapses / Q000187:drug effects
D008767:Methylmercury Compounds; D010396:Penicillamine