Reductions in N-acetylaspartylglutamate and the 67 kDa form of glutamic acid decarboxylase immunoreactivities in the visual system of albino and pigmented rats after optic nerve transections

This study compares the immunohistochemical distributions of N-acetylaspartylglutamate (NAAG) and the large isoform of the gamma-aminobutyric acid (GABA)-synthesizing enzyme glutamic acid decarboxylase (GAD(67)) in the visual system of albino and pigmented rats. Most retinal ganglion cells and their axons were strongly immunoreactive for NAAG, whereas GAD(67) immunoreactivity was very sparse in these cells and projections. In retinorecipient zones, NAAG and GAD(67) immunoreactivities occurred in distinct populations of neurons and in dense networks of strongly immunoreactive fibers and synapses. Dual-labeling immunohistochemistry indicated that principal neurons were stained for NAAG, whereas local interneurons were stained for GAD(67). In contrast to the distribution observed in retinorecipient zones, most or all neurons were doubly stained for NAAG and GAD(67) in the thalamic reticular nucleus. Ten days after unilateral optic nerve transection, NAAG-immunoreactive fibers and synapses were substantially reduced in all contralateral retinal terminal zones. The posttransection pattern of NAAG-immunoreactive synaptic loss demarcated the contralateral and ipsilateral divisions of the retinal projections. In addition, an apparent transynaptic reduction in GAD,, immunoreactivity was observed in some deafferented areas, such as the lateral geniculate. These findings suggest a complicated picture in which NAAG and GABA are segregated in distinct neuronal populations in primary visual targets, yet they are colocalized in neurons of the thalamic reticular nucleus. This is consistent with NAAG acting as a neurotransmitter release modulator that is coreleased with a variety of classical transmitters in specific neural pathways. (C) 2003 Wiley-Liss, Inc.