Acetylcholinesterase induces long-term potentiation in CA1 pyramidal cells by a mechanism dependent on metabotropic glutamate receptors.
Acetylcholinesterase (AChE) has additional functions within the central nervous system that are unrelated to cholinergic transmission. In the cerebellar cortex AChE has been shown to potentiate synaptic responses evoked by excitatory amino acids. Because AChE is also secreted from the terminal regions of cholinergic nerves within the hippocampus, this study investigates the actions of AChE on synaptic transmission in guinea pig hippocampal slices. Application of AChE produced a long-lasting potentiation of both the field epsp and the resulting population spike evoked by stimulation of the Schaffer/commissural-CA1 pathway. This effect was independent of any cholinergic receptor stimulation since it persisted in the presence of the cholinergic antagonists atropine and mecamylamine. Furthermore, the effect was not mimicked by butyrylcholinesterase despite its cholinolytic activity. However, the effect of AChE was dependent on metabotropic glutamate receptor stimulation since it was prevented by the metabotropic receptor antagonist (+/-)-alpha-methyl-4-carboxyphenylglycine. Perfusion with AChE therefore induces a long-lasting potentiation of hippocampal synaptic transmission which is reminiscent of the classical LTP produced by tetanic stimulation. Consequently the secreted protein could play an important role in the molecular mechanisms of learning and memory in vertebrates.
Appleyard
M E
ME
Department of Physiology, Royal Free Hospital School of Medicine, London, UK.
D000110:Acetylcholinesterase / Q000494:pharmacology*; D000818:Animals; D001285:Atropine / Q000494:pharmacology; D006168:Guinea Pigs; D006624:Hippocampus / Q000502:physiology; D017774:Long-Term Potentiation / Q000187:drug effects*; D008464:Mecamylamine / Q000494:pharmacology; D017966:Pyramidal Cells / Q000187:drug effects*; D018094:Receptors, Metabotropic Glutamate / Q000502:physiology*; D009435:Synaptic Transmission / Q000187:drug effects
D018094:Receptors, Metabotropic Glutamate; D008464:Mecamylamine; D001285:Atropine; D000110:Acetylcholinesterase