Relay cells, not interneurons, of cat's lateral geniculate nucleus contain N-acetylaspartylglutamate.

N-acetylaspartylglutamate (NAAG) is an endogenous brain dipeptide that satisfies many of the criteria for a neurotransmitter. We have previously identified NAAG immunoreactivity in neurons of the lateral geniculate nucleus (LGN) of the cat and monkey. To determine whether all LGN neurons contain NAAG, we treated sections of cat LGN with affinity-purified antibodies to NAAG and counterstained them with thionin. The larger neurons contained NAAG, but the smaller neurons did not. We treated other sections with antiserum to glutamic acid decarboxylase (GAD), the rate-limiting enzyme in the synthesis of gamma-aminobutyric acid (GABA), in order to label interneurons of the LGN. In these sections, the smaller cells were labeled; the larger neurons were not. We hypothesized that NAAG was present in relay cells, but not interneurons. We used two double-labeling paradigms to test this hypothesis. We combined immunocytochemistry for NAAG using a fluorescent secondary antibody with either (1) fluorescent retrograde tracers (true blue, granular blue, rhodamine beads, or propidium iodide) injected into areas 17 and/or 18 or (2) immunocytochemistry for GAD using a second fluorescent secondary antibody. In the LGN, over 99% of retrogradely labeled cells contained NAAG, but few GAD-positive neurons did. In contrast, neurons of the perigeniculate nucleus contained both NAAG and GAD, demonstrating that staining by one set of antisera did not inhibit staining by the other and that perigeniculate neurons are chemically distinct from the interneurons of the LGN. We conclude that in LGN, the relay cells, which project to visual cortex, contain NAAG, whereas most of the interneurons, which contain GABA, do not.