Facilitatory but nonessential role of the muscarinic cholinergic system in the generation of long-term potentiation of population spikes in the dentate gyrus in vivo.

The role of the muscarinic cholinergic system in the generation of LTP in the medial perforant path-dentate granule cell synapses in vivo was investigated using anesthetized rats. Cholinergic denervation with AF64A, a cholinergic toxin, did not significantly affect LTP induced by a strong tetanus (100 pulses at 100 Hz), but attenuated the LTP induced by a weak tetanus (30 pulses at 60 Hz). The i.c.v. injection of scopolamine (1.5-50 nmol) did not significantly affect the LTP induced by the strong tetanus but attenuated the magnitude of LTP produced by the weak tetanus in a concentration-dependent manner. These results suggest that the cholinergic system is not essential for induction of LTP by strong stimuli but plays a role in facilitating the generation of LTP by weak stimuli. Furthermore, the induction of LTP by a weak tetanus was blocked by pirenzepine but affected by neither AF-DX116 nor 4-diphenylacetoxy-N-methylpiperidine. The LTP-facilitatory action of the cholinergic system is probably mediated by muscarinic M1 receptors.