We have employed axonal transport techniques to study the organization of projections from the medullary reticular formation (RF) to the forebrain of the North American opossum. The results of retrograde transport studies using large injections of horseradish peroxidase (HRP), wheat germ agglutinin conjugated to HRP (WGA-HRP), and fluorescent markers suggest that all nuclei of the medullary RF project to the forebrain although the parvocellular reticular nucleus makes only a very small contribution. When injections of 3H-leucine or WGA-HRP are centered within areas shown by the retrograde transport studies to innervate the forebrain, characteristic patterns of orthograde labeling are produced. In most cases labeled axons form a major pathway which splits into dorsal and ventral divisions. The dorsal division innervates the parafascicular and central nuclei of the thalamus as well as the pretectum. In contrast, the ventral division projects to the lateral hypothalamus, the zona incerta, the ventral and dorsal lateral geniculate nuclei, the lateral part of the ventrobasal nucleus of the thalamus, the lateral preoptic area, the septal-diagonal band region, and the cerebral cortex. When injections are centered within specific ventrolateral areas of the medullary RF, ventral division labeling is also found within the dorsomedial, paraventricular and supraoptic nuclei of the hypothalamus. Relatively small injections of HRP or WGA-HRP into specific areas of the forebrain produce labeling which suggests that some areas receive projections from all nuclei of the medullary RF, whereas others do not. Our results suggest that forebrain projections of the medullary RF, like those to the spinal cord, are connectionally heterogeneous.

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