Excitatory amino acid projections to the periaqueductal gray in the rat: A retrograde transport study utilizing d[³H]aspartate and [³H]GABA

The afferents to the periaqueductal gray utilizing excitatory amino acid transmitters have been described in rat brain by autoradiography following microinfusion and retrograde transport of d[³H]aspartate. Parallel experiments employing injections of [³H]GABA established that the retrograde labelling found with d[³H]aspartate was transmitter-selective. Following infusion of d[³H]aspartate, perikaryal labelling was found in nine subcortical areas, particularly infralimbic and cingulate cortices, with a predominance of ipsilateral labelled perikarya. Heaviest cortical labelling was localized in perirhinal cortex, in an extensive band of cells adjoining the rhinal sulcus. The hypothalamus contained the heaviest perikaryal labelling within brain: d[³H]aspartate labelled cells in 11 hypothalamic and mammillary nuclei. Intense bilateral labelling was obtained in ventromedial hypothalamus, although the number of perikarya was lower contralaterally. d[³H]Aspartate also produced heavy ipsilateral labelling of perikarya in posterior hypothalamus. Labelling patterns in cortex and hypothalamus were precise and topographic, and [³H]GABA never labelled cells in these regions. Other telencephalic and diencephalic areas containing prominent, retrogradely labelled cells were the lateral septum, amygdala, zona incerta and lateral habenula. The relative density of labelled cells in mesencephalic areas was much lower than that found in cortex and hypothalamus, although d[³H]aspartate labelled a moderate number of perikarya in the inferior colliculus and cuneiform nucleus. A smaller number of heavily labelled cells was found in the parabrachial nuclei, Kolliker-Fuse nucleus and laterodorsal tegmental nucleus. Only occasional labelled perikarya were observed in the myencephalon. Low densities of labelled cells were found after the injection of [³H]GABA into the periaqueductal gray, and the only regions in which a small number of perikarya were labelled by both [³H]GABA and d[³H]aspartate were the dorsal raphe and parabrachial nuclei. Overall, the retrograde transport of d[³H]aspartate revealed a complex topographic and convergent network of afferent pathways to the periaqueductal gray likely to utilize an excitatory amino acid transmitter. Our findings confirm the selectivity of this neurochemical mapping technique and provide evidence that hypothalamic, habenular, subthalamic and cuneiform afferents to the periaqueductal gray utilize an acidic amino acid as their transmitter. They also confirm that corticofugal afferents to periaqueductal gray utilize an excitatory amino acid.