COMPARATIVE DISTRIBUTION OF N-ACETYLASPARTYLGLUTAMATE AND GAD(67) IN THE CEREBELLUM AND PRECEREBELLAR NUCLEI OF THE RAT UTILIZING ENHANCED CARBODIIMIDE FIXATION AND IMMUNOHISTOCHEMISTRY

The most prevalent peptide in the nervous system, N-acetylaspartylglut amate (NAAG), specifically activates N-methyl D-aspartate (NMDA) recep tors and a subclass of metabotropic glutamate receptors. One action of this peptide may be to modulate the release of other neurotransmitter s, including gamma-aminobutyric acid (GABA). The present study describ es the cellular distribution of NAAG, relative to GABA, in the cerebel lum and precerebellar nuclei as a foundation for further physiological investigations. Numerous cells of origin for messy fibers, including many of the larger neurons of the pontine nuclei, lateral reticular nu clei, vestibular nuclei, reticulotegmental nuclei, and spinal grey, we re moderately to strongly stained for NAAG. Many NAAG-labeled fibers w ere clearly visible in the cerebellar peduncles and central white matt er. Messy fibers and messy endings were among the most prominent NAAG- immunoreactive elements in the cerebellar cortex. Most neurons in the inferior olive were not stained for NAAG, and only sparse, lightly imm unoreactive, climbing fiber-like endings could be identified in restri cted regions of the cortical molecular layer. Purkinje neurons ranged from nonreactive to moderately positive, with the great majority being unstained. Cerebellar granule cells did not exhibit any NAAG immunore activity. A population of neurons in the deep cerebellar nuclei was hi ghly immunoreactive for NAAG. Additionally, many neurons of the red nu cleus were intensely stained for NAAG. Comparisons with staining for t he 67 kD form of glutamic acid decarboxylase in serial sections reveal ed complementary distributions, with NAAG in excitatory pathways and c ell groups, and glutamic acid decarboxylase in inhibitory systems. The se findings suggest a significant functional involvement of NAAG in th e excitatory afferent and efferent projection systems and provide an a natomical basis for investigations into the interactions of NAAG and G ABA in the cerebellum. (C) 1994 Wiley-Liss, Inc.