That the hypothalamus exerts an important regulatory influence on the autonomic nervous system has long been known1, 6, s, but the exact pathways through which this influence is mediated have not been established. Physiological studies, principally by Ranson, Magoun and their co-workers, have indicated that there are descending hypothalamic pathways which extend caudally through the midbrain tegmentum into the lateral funiculus of the spinal cord to reach the intermediolateral cell column. These experiments, combining electrical stimulation and lesions at various levels, established that the descending pathways are bilateral, some fibers crossing to the contralateral side at virtually all levelsT, 1~. However, it was impossible to determine from studies of this kind whether the pathways involved are direct or polysynaptic. From time to time reports have appeared in the neuroanatomical literature suggesting that there may be a direct input from the hypothalamus to the preganglionic sympathetic outflow in the spinal cord 2,~ 4 but, as yet, these have not been confirmed, and in most experimental studies using axonal degeneration techniques, it has not been possible to trace degenerating fibers much beyond the caudal midbrain or rostral ponsS, t3. As a result, the concensus of opinion has been that the hypothalamus influences the autonomic centers of the brain stem and spinal cord through a system of poorly defined connections through the brain stem reticular formationS, 5, 1L

This issue has recently been re-opened by the observation of Kuypers and Maisky 9 that certain neurons in the hypothalamus can be retrogradely labeled by injections of the enzyme marker horseradish peroxidase (HRP) into the spinal cord. In view of the importance of unequivocally establishing whether or not direct hypothalamo-autonomic connections exist, we have carried out a series of experiments similar to those of Kuypers and Maisky, using the retrograde transport of HRP from various brain stem and spinal autonomic centers, and have complemented these observations by studying the anterograde transport of radioactively labeled proteins from the hypothalamus to these centers, in the cat, rat and monkey.