Response of nucleus raphe magnus neurons to electrical stimulation of nucleus cuneiformis: Role of acetylcholine

Abstract

There is considerable evidence that cells in the ventral medulla which includes nucleus raphe magnus (NRM) and nucleus magnocellularis are involved in a descending pain inhibitory system. Anatomical studies indicate a strong projection from nucleus cuneiformis (NCF) to the ventral medulla and histochemical studies suggest that many NCF neurons are cholinergic. Therefore, we investigated the effect of NCF stimulation on NRM unit activity and explored the possible role of acetylcholine (ACh) in this interaction. Of 180 NRM neurons examined, 43% were excited and 14% were inhibited by NCF stimulation. The average latency to the peak excitatory response was about 14 ms with a range of 5–32 ms. There was a tendency for the response latencies to cluster around 5 and 14 ms. Inhibitory responses were between 10 and 65 ms in duration. The anatomical specificity of the effective stimulation site was assessed by determining the response of a given NRM neuron to stimulation of areas dorsal and ventral as well as within NCF. The most reliable and intense responses of NRM neurons was observed with electrode placements within NCF. The most effective NCF region for activating NRM neurons corresponded to that region of NCF that contains a large population of neurons that project directly to NRM as seen in the present histochemical studies. The involvement of ACh in the interaction between NCF and NRM was examined with iontophoretic application of ACh and its antagonists. Of NRM neurons that responded to ACh, 79% were excited, an effect which was blocked by scopolamine. Comparison of the effect of both NCF stimulation and ACh iontophoresis on the same NRM neuron revealed a highly significant relationship between the two responses suggesting that the effect of NCF stimulation on NRM unit activity may be mediated by a cholinergic synapse. Furthermore, the response of 60% of NRM neurons driven by NCF stimulation could be partially or completely blocked by scopolamine iontophoresis. These data suggest that a cholinergic projection plays a role in mediating the effect of NCF on NRM unit activity; however, other excitatory transmitters may also be important.