Ultrastructural morphometric analysis of GABA-immunoreactive terminals in the ventrocaudal periaqueductal grey: analysis of the relationship of GABA terminals and the GABAA receptor to periaqueductal grey-raphe magnus projection neurons

Abstract

The periaqueductal grey (PAG) plays an important role in the descending modulation of nociception. Inhibitory influences of GABAergic terminals, located within the periaqueductal grey, are thought to play a role in antinociception by influencing the activity of neurons that project to the nucleus raphe magnus and adjacent reticular nuclei. The present study utilized electron microscopic immunocytochemistry to quantitate the normal neuronal associations of GABA-immunoreactive terminals, and to visualize the neuronal distribution of the GABAA receptor in the ventrolateral periaqueductal grey of the rat. Of particular interest was a quantitative description of the interaction between GABA-immunoreactive axon terminals and periaqueductal grey neurons that were retrogradely-labelled from the nucleus raphe magnus and adjacent medullary reticular nuclei. Most terminals were observed to be immediately apposed only to two or three dendrites, although axonal and perikaryal associations were also observed. In the ventrolateral periaqueductal grey, 37.5% of all GABA-immunoreactive terminals were adjacent to periaqueductal grey-nucleus raphe magnus and periaqueductal grey-reticular nucleus projection neurons. Symmetrical synapses with these retrogradely-labelled neurons were formed by 17% of GABA-immunoreactive terminals in the ventrolateral periaqueductal grey. We also noted that 13.2% of the GABA-immunoreactive terminals formed symmetrical synapses with GABA-immunoreactive dendrites in the periaqueductal grey, and occasionally those dendrites were retrogradely labelled. Only 0.8% of the GABA-immunoreactive terminals formed putative symmetrical synapses with other GABA-immunoreactive terminals. Consistent with these findings, GABAA receptor immunoreactivity was only associated with dendrites and perikarya in neurons of the ventrolateral PAG. These results are consistent with an inhibitory role for GABA on PAG neurons, a configuration required by hypothetical models for opoid disinhibitory circuitry within the PAG. In addition, the data further suggest that other kinds of GABAergic connections may be important in descending antinociception, and that a population of GABAergic PAG projection neurons exists that may be inhibitory within nucleus raphe magnus and the adjacent reticular nuclei.