Periaqueductal gray neurons monosynaptically innervate extranuclear noradrenergic dendrites in the rat pericoerulear region

Previous reports using light microscopy have provided anatomical evidence t hat neurons in the ventrolateral periaqueductal gray (PAG) innervate the me dial pericoerulear dendrites of noradrenergic neurons in the nucleus locus coeruleus (LC). The present study used anterograde tracing and electron mic roscopic analysis to provide more definitive evidence that neurons in the v entrolateral PAG form synapses with the somata or dendrites of noradrenergi c LC neurons. Deposits of either biotinylated dextran amine or Phaseolus vu lgaris leucoagglutinin into the rat ventrolateral FAG labeled a moderate to high number of axons in the region of the medial pericoerulear region and Barrington's nucleus, but a relatively low number were labeled in the nucle ar core of the LC. Ultrastructural analysis of anterogradely labeled termin als at the levels of the rostral (n = 233) and caudal (n = 272) subdivision s of the LC indicated that approximately 20% of these form synapses with ty rosine hydroxylase-immunoreactive dendrites; most of these were located in the medial pericoerulear region. In rostral sections, about 12% of these we re symmetric synapses, 9% were asymmetric synapses, and 79% were membrane a ppositions without clear synaptic specializations. In caudal sections, abou t 30% were symmetric synapses, 11% were asymmetric synapses, and 59% were a ppositions. In both rostral and caudal sections, 60% of the anterogradely l abeled terminals formed synapses with noncatecholamine dendrites, and 20% f ormed axoaxonic synapses. These results provide direct evidence for monosyn aptic projections from neurons in the ventrolateral FAG to the extranuclear dendrites of noradrenergic LC neurons. This monosynaptic pathway may media te in part the analgesia, reduced responsiveness to external stimuli, and d ecreased excitability of somatic motoneurons produced by stimulation of neu rons in the ventrolateral PAG. J. Comp. Neurol. 427:649-662, 2000. (C) 2000 Wiley-Liss, Inc.