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

作者：Tang Mingliang; Luo Le; Zhu Damiao; Wang Ming; Luo Yunyun; Wang Huili; Ruan Di Yun^*

来源：Naunyn-Schmiedeberg's Archives of Pharmacology, 2009, 379(1): 37-45.

DOI：10.1007/s00210-008-0344-1

• Carbachol
• Hippocampus
• Lead
• Learning and memory
• Muscarinic receptor

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

• 出版日期2009-1
• 单位中国科学技术大学