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

Previous reports using light microscopy have provided anatomical evidence that neurons in the ventrolateral periaqueductal gray (PAG) innervate the medial pericoerulear dendrites of noradrenergic neurons in the nucleus locus coeruleus (LC). The present study used anterograde tracing and electron microscopic analysis to provide more definitive evidence that neurons in the ventrolateral PAG form synapses with the somata or dendrites of noradrenergic LC neurons. Deposits of either biotinylated dextran amine or Phaseolus vulgaris leucoagglutinin into the rat ventrolateral PAG 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 nuclear core of the LC. Ultrastructural analysis of anterogradely labeled terminals at the levels of the rostral (n = 233) and caudal (n = 272) subdivisions of the LC indicated that approximately 20% of these form synapses with tyrosine hydroxylase-immunoreactive dendrites; most of these were located in the medial pericoerulear region. In rostral sections, about 12% of these were symmetric synapses, 9% were asymmetric synapses, and 79% were membrane appositions without clear synaptic specializations. In caudal sections, about 30% were symmetric synapses, 11% were asymmetric synapses, and 59% were appositions. In both rostral and caudal sections, 60% of the anterogradely labeled terminals formed synapses with noncatecholamine dendrites, and 20% formed axoaxonic synapses. These results provide direct evidence for monosynaptic projections from neurons in the ventrolateral PAG to the extranuclear dendrites of noradrenergic LC neurons. This monosynaptic pathway may mediate in part the analgesia, reduced responsiveness to external stimuli, and decreased excitability of somatic motoneurons produced by stimulation of neurons in the ventrolateral PAG.