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Recent anatomic and physiologic experiments revealed that a major afferent to the nucleus locus coeruleus (LC) is the nucleus paragigantocellularis (PGi) in the rostral ventrolateral medulla (Aston- Jones et al., 1986). In the present studies, responses of LC neurons to electrical activation of PGi were characterized in anesthetized rats. Low-intensity stimulation of PGi synaptically activated 73% of LC neurons at short latencies (mean onset, 11.3 msec), while a smaller population (16%) of LC neurons exhibited purely inhibitory responses. The excitatory transmission from PGi to LC was pharmacologically analyzed, revealing it to be resistant to cholinergic receptor antagonism, but completely abolished by the excitatory amino acid (EAA) antagonists kynurenic acid and gamma-D-glutamylglycine. The specific N- methyl-D-aspartate antagonist 2--amino-7-phosphonoheptanoic acid (AP7) and the preferential quisqualate receptor antagonist glutamate diethyl ester (GDEE) did not block LC responses to PGi stimulation, leading us to the tentative conclusion that EAAs may operate primarily at a kainate-type receptor on LC neurons to effect excitation from PGi. In addition to their blockade of PGi-evoked activity, kynurenic acid and DGG exerted a similar, simultaneous blockade of the characteristic excitation of LC neurons evoked by electrical stimulation of the hindpaw. These and other results indicate that the proposed EAA pathway from PGi may serve as a final link in a variety of sensory inputs to LC.

Activation of locus coeruleus from nucleus paragigantocellularis: a new excitatory amino acid pathway in brain