title: Muscarinic cholinergic modulation of synaptic transmission and plasticity in rat hippocampus following chronic lead exposure.
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 microM CCh significantly enhanced tetanus-induced long-term potentiation (LTP), while 5 microM 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 microM 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 microM CCh was reduced by either pirenzepine or M-105. (3) Furthermore, paired-pulse facilitation (PPF) was not affected by 0.1 microM CCh in control and Pb2+-exposed rats but was increased by 5 microM 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.
authors: Department of Neurobiology and Biophysics, School of Life Sciences, University of Science and Technology of China, Hefei, Anhui, 230027, People's Republic of China.
authors: Mingliang
authors: M
authors: Tang
authors: Le
authors: L
authors: Luo
authors: Damiao
authors: D
authors: Zhu
authors: Ming
authors: M
authors: Wang
authors: Yunyun
authors: Y
authors: Luo
authors: Huili
authors: H
authors: Wang
authors: Di-Yun
authors: DY
authors: Ruan
mesh_terms: D000818:Animals; D002217:Carbachol / Q000494:pharmacology; D003959:Diamines / Q000494:pharmacology; D004785:Environmental Pollutants / Q000633:toxicity*; D019706:Excitatory Postsynaptic Potentials; D005260:Female; D006624:Hippocampus / Q000187:drug effects* / Q000502:physiology; D066298:In Vitro Techniques; D007854:Lead / Q000633:toxicity*; D007858:Learning / Q000187:drug effects; D017774:Long-Term Potentiation / Q000187:drug effects / Q000502:physiology; D008297:Male; D008568:Memory / Q000187:drug effects; D018721:Muscarinic Agonists / Q000494:pharmacology*; D018727:Muscarinic Antagonists / Q000494:pharmacology; D009473:Neuronal Plasticity / Q000187:drug effects* / Q000502:physiology; D010890:Pirenzepine / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D011976:Receptors, Muscarinic / Q000502:physiology; D009435:Synaptic Transmission / Q000187:drug effects* / Q000502:physiology
chemical_list: D003959:Diamines; D004785:Environmental Pollutants; D018721:Muscarinic Agonists; D018727:Muscarinic Antagonists; D011976:Receptors, Muscarinic; D007854:Lead; D010890:Pirenzepine; D002217:Carbachol; C054938:methoctramine