Ultrastructural analysis of ventrolateral periaqueductal gray projections to the A7 catecholamine cell group

Stimulation of neurons in the ventrolateral periaqueductal gray produces antinociception that is mediated in part by pontine noradrenergic neurons. Previous light microscopic analysis provided suggestive evidence for a direct projection from neurons in the ventrolateral periaqueductal gray to noradrenergic neurons in the A7 cell group that innervate the spinal cord dorsal horn. Therefore, the present ultrastructural study used anterograde tracing combined with tyrosine hydroxylase immunoreactivity to provide definitive evidence that neurons in the ventrolateral periaqueductal gray form synapses with the somata and dendrites of noradrenergic neurons of the A7 cell group. Injections of the anterograde tracers biotinylated dextran amine or Phaseolus vulgaris leucoagglutinin into the ventrolateral periaqueductal gray of Sasco Sprague-Dawley rats yielded a dense innervation in the region of the lateral pons containing the A7 cell group. Electron microscopic analysis of anterogradely labeled terminals (n=401) in the region of the A7 cell group indicated that approximately 10% of these formed plasmalemmal appositions to tyrosine hydroxylase-immunoreactive dendrites with no intervening astrocytic processes. About 23% of these were asymmetric synapses, 10% were symmetric synapses, and 67% did not exhibit clearly differentiated synaptic specializations. The majority of anterogradely labeled terminals (60%) formed plasmalemmal appositions with dendrites and somata that lacked detectable tyrosine hydroxylase immunoreactivity. About 35% of these were symmetric synapses, 9% were asymmetric synapses and 56% did not form synaptic specializations. Approximately 30% of all anterogradely labeled terminals displayed features characteristic of axo-axonic synapses.The present results provide direct ultrastructural evidence to support the hypothesis that the analgesia produced by stimulation of neurons in the ventrolateral periaqueductal gray is mediated, in part, by activation of spinally projecting noradrenergic neurons in the A7 catecholamine cell group.