RELATIVE SURVIVAL OF STRIATAL PROJECTION NEURONS AND INTERNEURONS AFTER INTRASTRIATAL INJECTION OF QUINOLINIC ACID IN RATS

An excitotoxic process mediated by the NMDA type glutamate receptor ma y be involved in striatal neuron death in Huntington's disease (HD). T o explore this possibility, we have injected an NMDA-receptor-specific excitotoxin, quinolinic acid (QA), into the striatum in adult rats an d 2-4 months postlesion explored the relative patterns of survival for the various different types of striatal projection neurons and intern eurons and for the striatal efferent fibers in the different striatal projection areas. The perikarya of specific types of striatal neurons were identified by neurotransmitter immunohistochemical labeling or by retrograde labeling from striatal target areas, while the striatal ef ferent fiber plexuses were identified by neurotransmitter immunohistoc hemical labeling. The pattern of survival for the perikarya of each ne uron type as a function of distance from the center of the injection s ite was determined, and the relative survival of each type was compare d. For the fibers in target areas, computer-assisted image analysis wa s used to determine the degree of fiber loss for each projection targe t. In the study of perikaryal vulnerability, we found that the somatos tatin-neuropeptide Y (SS/NPY) interneurons were the most vulnerable to QA and the cholinergic neurons were invulnerable to QA. The perikarya of all projection neuron types (striatopallidal, striatonigral, and s triato-entopeduncular) were less vulnerable than the SS/NPY interneuro ns and more vulnerable than the cholinergic interneurons. Among projec tion neuron perikarya, there was evidence of differential vulnerabilit y, with striatonigral neurons appearing to be the most vulnerable. Exa mination of immunolabeled striatal fibers in the striatal target areas indicated that striato-entopeduncular fibers better survived intrastr iatal QA than did striatopallidal or striatonigral fibers. The apparen t order of vulnerability observed in this study among projection neuro ns and/or their efferent fiber plexuses and the invulnerability observ ed in this study of cholinergic interneurons is similar to that observ ed in HD. The vulnerability of the SS/NPY interneurons to QA is, howev er, in stark contrast to their invulnerability in HD. The results thus suggest that although the excitotoxin hypothesis of striatal neuron d eath in KD has merit, QA injections into adult rat striatum do not str ictly mimic the outcome in HD. This suggests that either adult rats ar e not a completely suitable subject for mimicking HD or the HD excitot oxic process does not involve a freely circulating excitotoxin such as QA. (C) 1994 Academic Press, Inc.