Blair H. Turner

MPTP produces a pattern of nigrostriatal degeneration which coincides with the mosaic organization of the caudate nucleus.

In the normal dog we have found that cholinesterase and tyrosine hydroxylase (TH) histochemistry define a mosaic structure of the caudate nucleus that is similar to that described in other species. To determine if nigrostriatal afferents interlocked with this mosaic we injected dogs with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), a toxin specific to dopaminergic nigrostriatal cells. Alternate sections in the caudate nucleus stained for acetylcholinesterase, TH, and terminal degeneration revealed that the areas of densest degeneration were localized to the matrix, thereby outlining areas of much lighter degeneration which were coincident with the patches. This pattern of terminal degeneration suggests the existence of subcomponents of the dopaminergic nigrostriatal pathway, at least one of which might be selectively vulnerable to MPTP.

MPTP produces a mosaic-like pattern of terminal degeneration in the caudate nucleus of dog

This paper describes the spatial pattern of terminal degeneration in the caudate nucleus and putamen of the dog following an injection of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Marked inhomogeneities in the filed of terminal degeneration were found in the head of the caudate nucleus, which are reminiscent of the fundamental patch/matrix organization of the striatum. Using MPTP as a selective lesioning method, our results provide further evidence that the dopaminergic, nigrostriatal projection has a heterogeneous organization.

Distribution of the anterior commissure to the amygdaloid complex in the monkey.

Although the anterior commissure is known to carry fibers to the amygdaloid complex in infraprimate species4,8,16, no evidence for such a projection has been reported in primates6, 9. As part of an investigation 13 15 into the connections of the amygdala in the rhesus monkey (Macaca mulatta), we examined this question of commissural amygdaloid projections using the method of anterograde degeneration v. In one monkey, a control transection was made in that part of the body of the corpus callosum overlying the third ventricle through which the anterior commissure can be approached. In two experimental animals, the same part of the corpus callosum was cut, and the anterior commissure was visualized and sectioned. Details of the surgical procedures and the histological results of this type of commissural lesion have been reported previously 7 (see Fig. 2, Animal No. 56, for illustration). Following a survival period of 6 days, the monkeys were given a lethal dose of anesthetic and their brains prepared using the Fink-Heimer technique 5. In the control brain, no evidence of terminal degeneration was found either in the allocortex that covers the amygdala medially and anteriorly, or in the amygdala itself. In the experimental brains, however, degeneration was observed in both of these locations (see Figs. 2 and 3). In the allocortex, moderate degeneration was seen in the subdivision of entorhinal cortex that covers the anterior pole of the amygdala (Epol of Rose) ~I and also in the temporal prepiriform cortex (Prpy 3 of Rose tl) and the medial amygdaloid nucleus which cover the dorsomedial surface of the amygdala. In all 3 of these periamygdaloid allocortical areas, degeneration was heavier in layers IA and I B and progressively thinned out in layers II and III. Within the deep amygdaloid nuclei, moderately dense degeneration was seen in the lateral nucleus throughout its rostrocaudal and dorsoventral extent. In its mediolateral extent, degeneration was heavier in the lateral two-thirds than in the medial third. In addition, light degeneration was seen in the claustral area of the amygdala (as well as in the ventral part of

A PROGRESSIVE BALLOONING OF MYELINATED, TH-POSITIVE AXONS IS PRODUCED BY MPTP IN THE DOG

Systemic injections of l-methyl-4-phenyl-l,2,3,6-tetrahydropyridine (MPTP) produce selective degeneration of the dopaminergic neurons of the nigrostriatal pathway in some mammals such as dogs, monkeys, and humans but not others such as rats. The mechanism of MPTP’s actions has been studied by biochemical and pharmacological techniques which have found that MPTP’s toxicity requires its oxidation by glial MAO-B to l-methyl-4-phenylpyridinium (MPP+)1–3. Surprisingly, MPP+ is not selectively toxic to dopaminergic neurons but damages or kills most cells with which it comes into contact including hepatocytes and granule cells of the cerebellum4,5.