Amino Acids and N-acetyl-aspartyl-glutamate as Neurotransmitter Candidates in the Monkey Retinogeniculate Pathways

The lateral geniculate nucleus (LGNd) receives chemically identified inputs from brain stem structures, the thalamus and visual cortex. The identity of the neurotransmitter(s) in the retinal input, however, is unknown. To investigate the possibility that some amino acids and certain dipeptides, such as N-acetyl-aspartyl-glutamate (NAAG), fulfill this function, changes in their concentration were measured in the optic tract, parvocellular and magno-cellular segments of the LGNd, superior colliculus and visual cortex of six monkeys (Macaca fascicularis), seven days after right optic tractotomy. The LGNd was studied also in two additional macaques, three months after occipital lobectomy. Tissue was frozen within five minutes of death, regions were dissected with the micropunch technique, and substances were analyzed by HPLC. Of the ten compounds measured in the normal side, glutamate, glutamine, glycine, and alanine had homogeneous distributions. GABA was highest in the superior colliculus, cystathionine and NAAG decreased in the rostrocaudal direction, and N-acetyl-aspartate showed an opposite gradient of concentration. The heterogeneity in taurine and aspartate was less systematic. Optic tract section induced significant, large reductions in NAAG, glutamate and aspartate in the optic tract distal to the lesion. Significant decreases in NAAG, and to a lesser extent in glutamate, were observed in the LGNd. Changes in the dipeptide were apparent in both the parvocellular and magnocellular segments. Reductions in glutamate reached significance in the parvocellular laminae, and those of aspartate approached significance in the magnocellular division. No significant differences were detected in the superior colliculus and striate cortex. Occipital lobectomy produced large declines in aspartate and glutamate in the LGNd, as well as moderate reductions in alanine and GABA, and minor changes in glutamine and glycine. The results of optic tractotomy support the role of NAAG as a neurotransmitter candidate in the monkey retinogeniculate pathways; its significant decrease in both geniculate segments suggests that X- and Y- retinal axons utilize this substance. Although at times the reductions in glutamate or aspartate failed to reach significance, their role cannot be excluded. The findings after occipital lobectomy strongly favor these latter substances as corticogeniculate transmitters