Conclusions

NAAG is found in a subset of neurons throughout the brain and spinal cord of vertebrates ranging from turtle to man. Within those neurons, NAAG is found in all parts of the cell except the nucleus. In many cases the filling of dendrites and axons is sufficient to classify the types of neuron labeled. In other cases, double-labeling paradigms have been used.

Among mammals, the pattern of localization is remarkably consistent. NAAG is found in projection neurons at all stages from periphery up to cortex of all sensory systems except perhaps gustatory. In vestibular and somatosensory systems, only large ganglion cells are labeled, whereas in visual system, all or nearly all retinal ganglion cells are labeled. Various sensory relay cells in spinal cord and medulla are labeled, including cells of dorsal horn, Clarke's column, dorsal column nuclei and vestibular nuclei. Similarly, sensory thalamic relay cells are labeled, as are the mitral cells of the olfactory bulb. Subcortical projection neurons of the motor systems are labeled, down to and including those projecting to the periphery. Only in cerebral cortex is there significant variation: in cat, monkey and man, NAAG is seen in both pyramidal and non-pyramidal cells, whereas in rat it is seen only in non-pyramidal cells.

NAAG co-localizes with a variety of classical neurotransmitters. It is seen in subsets of cells that also label for acetylcholine, GABA, dopamine, nor-adrenaline, serotonin and somatostatin.

Finally, as has been reported for a variety of other neurotransmitters, the level of NAAG expression is regulated by neural activity.

9. ACKNOWLEDGMENTS

The author's research on NAAG was supported in part by NSF grants BNS-8811039 and IBN-9212426. Drs. Joseph H. Neale of Georgetown University and David Tieman of the University at Albany collaborated on much of the research. I thank Drs. Joe Neale and John Moffett for their generous contribution of antibodies.

10. QUESTION AND ANSWER SESSION

DR. COYLE: This presentation is open for discussion.

DR. BASLOW: Just one comment about the frog. Frog brain has no measurable NAA, and so it is a different kind of a brain structure. Apparently, it does have NAAG, though. I am not sure where that is.

DR. TIEMAN: What I was hoping you would comment upon was the activity dependent expression of NAAG.

DR. MOFFETT: As it relates to what I have seen, basically, in areas of thalamus, for example, where we have extremely high levels of glutamate input -- for example, ventrobasal thalamus and lateral geniculate, which receive large amounts of glutamatergic input -- the plexus of NAAG staining is incredibly dense.

I have a sense that what we are seeing with the down-regulation of NAAG in post-synaptic neurons like that is probably due to the lack of the glutamate input. In places where glutamate input is high, even if there are no glutamatergic cell bodies there, if the terminals are glutamatergic, then the level of NAAG staining in either interneurons or principal neurons in the area, and the expression of NAAG in synaptic terminals in the neuropil is very high.

DR. TIEMAN: Except in LGN, where the interneurons are not labeled.

DR. MOFFETT: Yes. Whereas in other places they are, like in neocortex.

PARTICIPANT: I will ask a question about your activities. Which -- I mean, the up-regulation of NAAG -- we have heard Dr. Ross, I think, talking about ways that that can be regulated. It is either due to a decrease in its breakdown or an increase in its synthesis. Do you have any inference from your -- or anyone else here -- of what might be happening?

DR. TIEMAN: I would be happy to hear from anyone else on this.

DR. LIEBERMAN: I will comment about it. To some extent, when you do stimulate, you do get an increase in synthesis, in some cases both NAAG and NAA, so there is some activity-dependent regulation.

DR. COYLE: I might mention that both John and our laboratories have shown loss of NAAG release with the optic nerve transection, both radiolabeled as well as endogenous NAAG, confirming not only the localization but also the functional significance of this process. Any other questions?

Thank you very much Dr. Tieman.

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