The Modulation Of Muscarinic System On Synaptic Transmission And Plasticity In Rat Hippocampus And The Effect Of Lead

The roles of the muscarinic acetylcholine receptors(mAChRs)in synaptic transmission and Plasticity at many areas of the central nervous system including the hippocampus,have been extensively studied.However,not much is known about the modulation of LTP through individual subtypes of mAChR(M1-M5 subtype).Lead, known as a heavy metal pollutant,is a neurotoxicant.Lead exposure impairs many neurotransmitter systems and nerve system function.Few has been reported about whether lead can affect muscarinic modulation.In this study,using electrophysiological methods,we investigated muscarinic modulation on synaptic transmission and Plasticity and the effect of lead on it.1)we investigated the involvement of each individual subtypes of mAChR in LTP induction by intrahippocampal administration of cholinergic ligands at the dentate gyrus(DG)of anaesthetized rats.We found atropine,an antagonist of mAChRs,suppressed the induction of LTP.This observation confirmed that the muscarinic system is involved in LTP.We then examined the effects of M1AChR antagonists(pirenzepine and telenzepine),M2/4AChR antagonists(Methoctramine and{11-[[2-[(diethylamino)methyl]-1-piperidinyl]acetyl]-5,11 -dihydro-6H-pyrido[2, 3-b][1,4]benzodiazepin-6-one}(AFDX-116)),and M3/5AChR antagonist (4-diphenylacetoxy-N-methylpiperidine methiodide(4-DAMP))on LTP.Our results showed that both M1AChR and M2/4AChR antagonists but not M3/5AChR antagonist suppressed the amplitude of LTP.We also examined the effects of these cholinergic ligands on basal synaptic transmission and found that only pirenzepine augmented the amplitude of population spike(PS).This study suggests that individual mAChR subtypes play different modulation roles in LTP induction in the DG of rats.2)we investigated the the muscarinic modulation in the CA1 area of hippocampal slices and the effect of lead on it.Carbachol is an agonist of cholinergic receptors.In this study,application of 5 M carbacbol by perfusion inhibited the amplitude of glutamatergic EPSC in rat hippocampal CA1 pyramidal neurons.This inhibition was maily mediated by mAChRs.With the nAChRs blocked by perfusion of mecamylamine(10 M),carbachol inhibited EPSC concentration-dependently; 5 M carbachol enhanced paired-pulse facilitation(PPF)and responses to 10 Hz train of pulses;5 M carbachol also reduced sEPSCs frequency and decreased the amplitudes and decay time of sEPSCs.In the same conditions,10 M lead showed no slgnificant effect on the amplitude of EPSC,but slightly weakened the inhibition of carbachol on EPSC;lead inhibited the enhancement of PPF and responses to 10 Hz train of pulses;and lead reduced the frequency and decay of sEPSCs,and blocked the effect of carbachol while did not has significant effect on sEPSCs amplitudes and the inhibition by carbachol.Cholinergic system modulates synaptic transmission and plasticity in hippocampus through pre- and postsynaptic mAChRs, and plays an important role in learning and memory.The effects of lead on the cholinergic modulation of glutamatergic synaptic transmission and plasticity might be involved in the impairment of learning and memory by lead.