Parasympathetic and Sympathetic Control of the Pancreas: A Role for the Suprachiasmatic Nucleus and Other Hypothalamic Centers That Are Involved in the Regulation of Food Intake RUUD M. BUIJS, 1 * SOO JIN CHUN, 1,2 AKIRA NIIJIMA, 3 HERMS J. ROMIJN, 1 AND KATSUYA NAGAI 2 1 Netherlands Institute for Brain Research, Meibergdreef 33, Amsterdam 1105 AZ, The Netherlands 2 Division of Protein Metabolism, Institute for Protein Research, Osaka University, 3-2 Yamada-oka, Suita, Osaka 565-0871, Japan 3 Niigata University School of Medicine, Niigata, Niigata 951-8510, Japan ABSTRACT To reveal brain regions and transmitter systems involved in control of pancreatic hormone secretion, specific vagal and sympathetic denervation were combined with injection of a retro- grade transsynaptic tracer, pseudorabies virus (PRV), into the pancreas. After sympathetic or vagal transsection first-order neurons were revealed in the dorsal motor nucleus of the vagus (DMV) or in preganglionic spinal cord neurons (SPN), respectively. Careful timing of the survival of the animals allowed the detection of cell groups in immediate control of these DMV or SPN neurons. A far larger number of cell groups is involved in the control of DMV than of SPN neurons. Examples are given of a high level of interaction between the sympathetic and para- sympathetic nervous system. Several cell groups project to both branches of the autonomic nervous system, sometimes even the same neurotransmitter is used, e.g., oxytocin neurons in the paraventricular nucleus and melanin-concentrating hormone and orexin neurons in the lateral hypothalamus project to both the DMV and SPN neurons. Moreover, the appearance of third- order neurons located in the sympathetic SPN after complete sympathectomy and in the DMV after complete vagotomy illustrates the possibility that motor neurons of the sympathetic and parasympathetic system may exchange information by means of interneurons. The presence of second-order neurons in prefrontal, gustatory, and piriform cortex may provide an anatomic basis for the involvement of these cortices in the cephalic insulin response. The observation that second-order neurons in both vagal and sympathetic control of the pancreas contain neuropep- tides that are known to play a role in food intake indicates a direct association between behavioral and autonomic functions. Finally, the observation of third-order neurons in the suprachiasmatic nucleus and ventromedial hypothalamus shows the modulatory action of the time of the day and metabolic state, respectively. J. Comp. Neurol. 431:405– 423, 2001. © 2001 Wiley-Liss, Inc. Indexing terms: glucagon; paraventricular nucleus; prefrontal cortex; circadian rhythm In mammals, the central nervous system (CNS) re- quires glucose as an essential source of energy. Therefore, to survive, mammals have to maintain their blood glucose within a narrow range by means of central and peripheral mechanisms (Oomura and Yoshimatsu, 1984; Choi et al., 1996; Dallman et al., 1999). Blood glucose concentration itself directly controls the secretion of the pancreatic hor- mones insulin and glucagon. Not surprisingly, because of the critical role glucose plays in the CNS, the brain also affects insulin and glucagon release through the auto- nomic nervous system (Frohman et al., 1967; Kaneto et *Correspondence to: Ruud M. Buijs, Netherlands Institute for Brain Research, Meibergdreef 33, Amsterdam 1105 AZ, The Netherlands. E-mail: r.buijs@nih.knaw.nl Received 17 July 2000; Revised 8 December 2000; Accepted 8 December 2000 THE JOURNAL OF COMPARATIVE NEUROLOGY 431:405– 423 (2001) © 2001 WILEY-LISS, INC.