COTRANSMITTER-MEDIATED LOCUS-COERULEUS ACTION ON MOTONEURONS

This article reviews evidence for a direct noradrenergic projection fr om the dorsolateral pontine tegmentum (DLPT) to spinal motoneurons. Th e existence of this direct pathway was first inferred by the observati on that antidromically evoked responses occur in single cells in the l ocus coeruleus (LC), a region within the DLPT, following electrical st imulation of the ventral horn of the lumbar spinal cord of the cat. We subsequently confirmed that there is a direct noradrenergic pathway f rom the LC and adjacent regions of the DLPT to the lumbar ventral horn using anatomical studies that combined retrograde tracing with immuno histochemical identification of neurotransmitters. These anatomical st udies further revealed that many of the noradrenergic neurons in the L C and adjacent regions of the DLPT of the cat that send projections to the spinal cord ventral horn also contain colocalized glutamate (Glu) or enkephalin (ENK). Recent studies from our laboratory suggest that Glu and ENK may function as cotransmitters with norepinephrine (NE) in the descending pathway from the DLPT. Electrical stimulation of the L C evokes a depolarizing response in spinal motoneurons that is only pa rtially blocked by alpha(1), adrenergic antagonists. In addition, NE m imicks only the slowly developing and not the fast component of LC-evo ked depolarization. Furthermore, the depolarization evoked by LC stimu lation is accompanied by a decrease in membrane resistance, whereas th at evoked by NE is accompanied by an increased resistance. That Glu ma y be a second neurotransmitter involved in LC excitation of motoneuron s is supported by our observation that the excitatory response evoked in spinal cord ventral roots by electrical stimulation of the LC is at tenuated by a non-N-methyl-D-aspartate glutamatergic antagonist. ENK m ay participate as a cotransmitter with NE to mediate LC effects on lum bar monosynaptic reflex (MSR) amplitude. Electrical stimulation of the LC has a biphasic effect on MSR amplitude, facilitation followed by i nhibition. Adrenergic antagonists block only the facilitatory effect o f LC stimulation on MSR amplitude, whereas the ENK antagonist naloxone reverses the inhibition. The chemical heterogeneity of the cat DLPT s ystem and the differential responses of motoneurons to the individual cotransmitters help to explain the diversity of postsynaptic potential s that occur following LC stimuli.