Acetylcholinesterase has a non-cholinergic neuromodulatory action in the guinea-pig substantia nigra.

Acetylcholinesterase is released within the substantia nigra from the soma/dendrites of nigrostriatal neurons. Previous work suggests that this phenomenon is independent of cholinergic systems, but rather serves to modulate the sensitivity of dopamine-containing nigrostriatal cells to synaptic events. This hypothesis was tested directly in the anaesthetized guinea-pig. Micro-infusion of acetylcholinesterase into the substantia nigra led to an increase in spontaneous firing of nigrostriatal neurons. Furthermore, the pattern of firing evoked by stimulation of the striatum was markedly enhanced. By contrast, administration of butyrylcholinesterase had no effect. It thus appears that acetylcholinesterase has a modulatory action on the firing of nigrostriatal cells, independent of hydrolysis of acetylcholine.