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Muscarinic cholinergic modulation of synaptic transmission and plasticity in rat hippocampus following chronic lead exposure

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Abstract

The cholinergic system is believed to be associated with learning and memory functions. Lead (Pb2+) is a well-known neurotoxic metal that causes irreversible damage to the central nervous system (CNS). To investigate whether Pb2+ interferes with cholinergic modulation, we examined the effects of carbachol (CCh), a muscarinic cholinergic agonist, on synaptic transmission and plasticity in the CA1 area of the hippocampus of developmentally Pb2+-exposed rats. The results showed that: (1) In both control and Pb2+-exposed rats, 0.1 μM CCh significantly enhanced tetanus-induced long-term potentiation (LTP), while 5 μM CCh induced a reversible depression of field excitatory postsynaptic potentials (fEPSPs). However, both the enhancement of LTP and depression of fEPSPs were significantly smaller in Pb2+-exposed rats than in controls, suggesting that the extent of the effect of CCh on the cholinergic system was depressed by Pb2+. (2) In Pb2+-exposed rats, the enhancement of LTP induced by 0.1 μM CCh was attenuated by pirenzepine, a M1AChR antagonist, but was not affected by methoctramine tetrahydrochloride (M-105), a M2/4AChR antagonist. The depression of fEPSPs induced by 5 μM CCh was reduced by either pirenzepine or M-105. (3) Furthermore, paired-pulse facilitation (PPF) was not affected by 0.1 μM CCh in control and Pb2+-exposed rats but was increased by 5 μM CCh in either group; the increase in PPF was less pronounced in Pb2+-treated when compared to control rats. These results suggested that cholinergic modulation could be impaired by Pb2+, and this kind of impairment might occur via different mAChR subtypes. Our study delineated the effects of Pb2+ on muscarinic modulation, and this might be one of the underlying mechanisms by which Pb2+ impairs learning and memory.

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Abbreviations

Ach:

acetylcholine

ACSF:

artificial cerebrospinal fluid

CCh:

carbachol

fEPSPs:

field excitatory postsynaptic potentials

LTP:

long-term potentiation

mAChRs:

muscarinic acetylcholine receptors

NMDA:

N-methyl-d-aspartate

Pb2+ :

lead

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Acknowledgments

This work was supported by the National Basic Research Program of China (no. 2002CB512907), the National Nature Science Foundation of China (nos. 30630057; 30670554; 30670662; 30672290), Academia Sinica (no. KZCX3-SW-437), China Postdoctoral Science Foundation (no. 20060400719), K. C. Wong Education Foundation of Hong Kong and Anhui High Education Natural Science Program (no. ZD2008010-2).

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  1. Department of Neurobiology and Biophysics, School of Life Sciences, University of Science and Technology of China, Hefei, Anhui, 230027, People’s Republic of China

    Mingliang Tang, Le Luo, Damiao Zhu, Ming Wang, Yunyun Luo, Huili Wang & Di-Yun Ruan

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  1. Mingliang Tang
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  2. Le Luo
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Correspondence to Di-Yun Ruan.

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Tang, M., Luo, L., Zhu, D. et al. Muscarinic cholinergic modulation of synaptic transmission and plasticity in rat hippocampus following chronic lead exposure. Naunyn-Schmied Arch Pharmacol 379, 37–45 (2009). https://doi.org/10.1007/s00210-008-0344-1

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