Release of acetylcholinesterase in the rat nigrostriatal pathway: relation to receptor activation and firing rate

Abstract

Acetylcholinesterase is released from both axon terminals and dendrites of nigrostriatal neurons. The relationship of this phenomenon to: (1) activation of receptors, and (2) firing rate, has been examined. In the first series of experiments, apomorphine or acetylcholine were infused into substantiae nigrae of urethane anaesthetized rats, via push-pull cannulae. In the ipsilateral striatum, the release of acetylcholinesterase was modified in a fashion reminiscent of the changes in firing rate induced by these drugs in nigrostriatal cells. Thus, application of acetylcholine into the substantia nigra induced an increase, while apomorphine induced a decrease in the release of acetylcholinesterase from the striatum. However, in the substantia nigra, the release of acetylcholinesterase did not follow this pattern: acetylcholine reduced local release, while apomorphine caused no change. In the second part of this study we studied the relationship between firing rate of nigrostriatal cells and the release of acetylcholinesterase. Two compounds known to block neuronal impulse flow were infused into the substantia nigra. These drugs were tetrodotoxin (a Na+ channel blocker), or gamma-hydroxybutyrate (a drug which blocks impulse flow specifically in dopaminergic cells). Both compounds reduced the release of acetylcholinesterase in the ipsilateral striatum. However, locally in the substantia nigra there was no decrease in release of the enzyme. In fact, following administration of gamma-hydroxybutyrate, there was a large Ca2+ dependent increase in release of acetylcholinesterase in the substantia nigra. These results suggest that release of acetylcholinesterase in the striatum may be linked to the discharge frequency of nigrostriatal neurons. On the other hand, release of acetylcholinesterase from the substantia nigra, which probably occurs from dendrites, is independent of Na+ mediated action potentials. This release may instead be associated with specific dendritic Ca2+ conductances.