Cerebellar Fastigial Nuclear Inputs and Peripheral Feeding Signals Converge on Neurons in the Dorsomedial Hypothalamic NucleusLi B.a · Guo C.-L.a · Tang J.b · Zhu J.-N.a · Wang J.-J.a
aDepartment of Biological Science and Technology and State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, and bModel Animal Research Center, Nanjing University, Nanjing, China
Jian-Jun Wang and Jing-Ning Zhu
School of Life Sciences, Mailbox 426
22 Hankou Road, Nanjing 210093 (China)
Tel./Fax +86 25 8359 2714, E-Mail email@example.com and firstname.lastname@example.org
Do you have an account?
Previous studies have indicated that neurons in the dorsomedial hypothalamic nucleus (DMN) receive feeding-related signals from the gastric vagal nerves, glycemia as well as leptin. On the other hand, it is intriguing that the cerebellum participates in regulating nonsomatic visceral activities including food intake via the direct cerebellohypothalamic projections. The present study was designed to examine, by using extracellular recordings in vivo in rats, whether the cerebellar fastigial nucleus (FN) could reach and converge with the feeding-associated gastric vagal, glycemia and leptin signals onto single DMN neurons. Of the 200 DMN neurons recorded, 104 (52%) responded to the cerebellar FN stimulation, in which 95 (91.3%) were also responsive to the gastric vagal stimulation, suggesting a convergence of cerebellar FN and gastric vagal inputs on the DMN neurons. Moreover, a summation of responses was observed (n = 10) when the cerebellar FN and gastric vagal nerve were simultaneously stimulated. Among the 18 DMN neurons receiving convergent inputs from the cerebellar FN and gastric vagal nerves, 16 (88.9%) cells also responded to the systemic administrations of glucose and leptin. These results demonstrated that the cerebellar FN-afferent inputs, together with the feeding signals from the gastric vagal nerves, blood glucose as well as leptin, converge onto single DMN neurons, suggesting that a somatic-visceral integration related to the feeding may occur in the DMN and the cerebellum may actively participate in the feeding regulation through the cerebellar FN-DMN projections.
© 2009 S. Karger AG, Basel
- Bellinger LL, Bernardis LL: The dorsomedial hypothalamic nucleus and its role in ingestive behavior and body weight regulation: lessons learned from lesioning studies. Physiol Behav 2002;76:431–442.
- Zhu JN, Guo CL, Li HZ, Wang JJ: Dorsomedial hypothalamic nucleus neurons integrate important peripheral feeding-related signals in rats. J Neurosci Res 2007;85:3193–3204.
- Fuller PM, Lu J, Saper CB: Differential rescue of light- and food-entrainable circadian rhythms. Science 2008;320:1074–1077.
- Gooley JJ, Schomer A, Saper CB: The dorsomedial hypothalamic nucleus is critical for the expression of food-entrainable circadian rhythms. Nat Neurosci 2006;9:398–407.
- Chou TC, Scammell TE, Gooley JJ, Gaus SE, Saper CB, Lu J: Critical role of dorsomedial hypothalamic nucleus in a wide range of behavioral circadian rhythms. J Neurosci 2003;23:10691–10702.
- Friedman JM, Halaas JL: Leptin and the regulation of body weight in mammals. Nature 1998;395:763–770.
- Bray GA: Afferent signals regulating food intake. Proc Nutr Soc 2000;59:373–384.
- Schwartz GJ: The role of gastrointestinal vagal afferents in the control of food intake: current prospects. Nutrition 2000;16:866–873.
- Campfield LA, Smith FJ: Blood glucose dynamics and control of meal initiation: a pattern detection and recognition theory. Physiol Rev 2003;83:25–58.
- Schwartz MW, Woods SC, Porte D Jr, Seeley RJ, Baskin DG: Central nervous system control of food intake. Nature 2000;404:661–671.
- Elmquist JK, Ahima RS, Elias CF, Flier JS, Saper CB: Leptin activates distinct projections from the dorsomedial and ventromedial hypothalamic nuclei. Proc Natl Acad Sci USA 1998;95:741–746.
- Shioda S, Funahashi H, Nakajo S, Yada T, Maruta O, Nakai Y: Immunohistochemical localization of leptin receptor in the rat brain. Neurosci Lett 1998;243:41–44.
- Zhu JN, Wang JJ: The cerebellum in feeding control: possible function and mechanism. Cell Mol Neurobiol 2008;28:469–478.
- Scalera G: Effects of corticocerebellar lesions on taste preferences, body weight gain, food and fluid intake in the rat. J Physiol (Paris) 1991;85:214–222.
- Mahler JM: An unexpected role of the cerebellum: involvement in nutritional organization. Physiol Behav 1993;54:1063–1067.
- Liu YJ, Gao JH, Liu HL, Fox PT: The temporal response of the brain after eating revealed by functional MRI. Nature 2000;405:1058–1061.
- Reis DJ, Golanov EV: Autonomic and vasomotor regulation. Int Rev Neurobiol 1997;41:121–149.
- Xu FD, Frazier DT: Modulation of respiratory motor output by cerebellar deep nuclei in the rat. J Appl Physiol 2000;89:996–1004.
Dietrichs E, Haines DE: Possible pathway for cerebellar modulation of autonomic response: micturition. Scand J Urol Nephrol 2002;210:16–20.
- Peng YP, Qiu YH, Chao BB, Wang JJ: Effect of lesions of cerebellar fastigial nuclei on lymphocyte functions of rats. Neurosci Res 2005;51:275–284.
- Peng YP, Qiu YH, Qiu J, Wang JJ: Cerebellar interposed nucleus lesions suppress lymphocyte function in rats. Brain Res Bull 2006;71:10–17.
- Ito M: Cerebellar long-term depression: characterization, signal transduction, and fuctional roles. Physiol Rev 2001;81:1143–1195.
- Schmahmann JD, Sherman JC: The cerebellar cognitive affective syndrome. Brain 1998;121:561–579.
- Martner J: Cerebellar influences on autonomic mechanisms: An experimental study in the cat with special reference to the fastigial nucleus. Acta Physiol Scand 1975;425:1–42.
- Dietrichs E, Haines DE, Røste GK, Røste LS: Hypothalamocerebellar and cerebellohypothalamic projections: circuits for regulating nonsomatic cerebellar activity? Histol Histopathol 1994;9:603–614.
- Haines DE, Dietrichs E, Mihailoff GA, McDonald EF: The cerebellar-hypothalamic axis: basic circuits and clinical observations. Int Rev Neurobiol 1997;41:83–107.
- Çavdar S, Şan T, Aker R, Şehirli U, Onat F: Cerebellar connections to the dorsomedial and posterior nuclei of the hypothalamus in the rat. J Anat 2001;198:37–45.
- Çavdar S, Onat F, Aker R, Şehirli U, Şan T, Yananli HR: The afferent connections of the posterior hypothalamic nucleus in the rat using horseradish peroxidase. J Anat 2001;198:463–472.
- Wang JJ, Pu YM, Wang T: Influences of cerebellar interpositus nucleus and fastigial nucleus on the neuronal activity of lateral hypothalamic area. Sci China C Life Sci 1997;40:176–183.
- Zhang YP, Ma C, Wen YQ, Wang JJ: Convergence of gastric vagal and cerebellar fastigial nuclear inputs on glycemia-sensitive neurons of lateral hypothalamic area in the rat. Neurosci Res 2003;45:9–16.
- Min B, Oomura Y, Katafuchi T: Responses of rat lateral hypothalamic neuronal activity to fastigial nucleus stimulation. J Neurophysiol 1989;61:1178–1184.
- Katafuchi T, Koizumi K: Fastigial inputs to paraventricular neurosecretory neurons studied by extra- and intracellular recordings in rats. J Physiol (London) 1990;421:535–551.
- Haywood JR, Fink GD, Buggy J, Phillips MI, Brody MJ: The area postrema plays no role in the pressor action of angiotensin in the rat. Am J Physiol Heart Circ Physiol 1980;239:H108–H113.
- Zhang ZH, Felder RB: Melanocortin receptors mediate the excitatory effects of blood-borne murine leptin on hypothalamic paraventricular neurons in rat. Am J Physiol Regul Integr Comp Physiol 2004;286:R303–R310.
Paxinos G, Watson C: The Rat Brain in Stereotaxic Coordinates, ed 4. San Diego, Academic Press, 1998.
- Yuan CS, Barber WD: Hypothalamic unitary responses to gastric vagal input from the proximal stomach. Am J Physiol Gastrointest Liver Physiol 1992;262:G74–G80.
- Yuan CS, Barber WD: Interactions of gastric vagal and peripheral nerves on single neurons of lateral hypothalamus in the cat. Am J Physiol Gastrointest Liver Physiol 1996;271:G858–G865.
- Oomura Y, Kimura K, Ooyama H, Maeno T, Iki M, Kuniyoshi M: Reciprocal activities of the ventromedial and lateral hypothalamic areas of cats. Science 1964;143:484–485.
- Orsini JC, Wiser AK, Himmi T, Boyer A: Sensitivity of lateral hypothalamic neurons to glycemia level: possible involvement of an indirect adrenergic mechanism. Brain Res Bull 1991;26:473–478.
- Himmi T, Boyer A, Orsini JC: Changes in lateral hypothalamic neuronal activity accompanying hyper- and hypoglycemias. Physiol Behav 1988;44:347–354.
- Yettefti K, Orsini JC, Perrin J: Characteristics of glycemia-sensitive neurons in the nucleus tractus solitarii: possible involvement in nutritional regulation. Physiol Behav 1997;61:93–100.
- Zhang YP, Zhu JN, Chen K, Li HZ, Wang JJ: Neurons in the rat lateral hypothalamic area integrate information from the gastric vagal nerves and the cerebellar interpositus nucleus. Neurosignals 2005;14:234–243.
- Zhu JN, Zhang YP, Song YN, Wang JJ: Cerebellar interpositus nuclear and gastric vagal afferent inputs reach and converge onto glycemia-sensitive neurons of the ventromedial hypothalamic nucleus in rats. Neurosci Res 2004;48:405–417.
- Zhu JN, Li HZ, Ding Y, Wang JJ: Cerebellar modulation on feeding-related neurons in rat dorsomedial hypothalamic nucleus. J Neurosci Res 2006;84:1597–1609.
- Wen YQ, Zhu JN, Zhang YP, Wang JJ: Cerebellar interpositus nuclear inputs impinge on paraventricular neurons of the hypothalamus in rats. Neurosci Lett 2004;370:25–29.
- Kita H, Oomura Y: An HRP study of the afferent connections to rat medial hypothalamic region. Brain Res Bull 1982;8:53–62.
- Bernardis LL, Bellinger LL: The dorsomedial hypothalamic nucleus revisited: 1998 update. Proc Soc Exp Biol Med 1998;218:284–306.
- Zhu JN, Yung WH, Chow BKC, Chan YS, Wang JJ: The cerebellar-hypothalamic circuits: potential pathways underlying cerebellar involvement in somatic-visceral integration. Brain Res Rev 2006;52:93–106.
- Colombel C, Lalonde R, Caston J: The effects of unilateral removal of the cerebellar hemispheres on motor functions and weight gain in rats. Brain Res 2002;950:231–238.
- Schmahmann JD, Doyon J, McDonald D, Holmes C, Lavoie K, Hurwitz AS, Kabani N, Toga A, Evans A, Petrides M: Three-dimensional MRI atlas of the cerebellum in proportional stereotaxic space. NeuroImage 1999;10:233–260.
- Tataranni PA, Gautier JF, Chen K, Uecker A, Bandy D, Salbe AD, Pratley RE, Lawson M, Reiman EM, Ravussin E: Neuroanatomical correlates of hunger and satiation in humans using positron emission tomography. Proc Natl Acad Sci USA 1999;96:4569–4574.
- Parsons LM, Denton D, Enga G, McKinley M, Shade R, Lancaster J, Fox PT: Neuroimaging evidence implicating cerebellum in support of sensory/cognitive processes associated with thirst. Proc Natl Acad Sci USA 2000;97:2332–2334.
- Pu YM, Wang JJ, Wang T, Yu QX: Cerebellar interpositus nucleus modulates neuronal activity of lateral hypothalamic area. NeuroReport 1995;6:985–988.
- Gzgzian DM, Kuzina MM, Tanasiĭchuk OF: Effect of the cerebellum on the motor activity of the stomach in the scorpion fish, Scorpaena porcus. Zh Evol Biokhim Fiziol 1978;14:408–410.
- Lam QL, Lu L: Role of leptin in immunity. Cell Mol Immunol 2007;4:1–13.
- Paraskevas KI, Liapis CD, Mikhailidis DP: Leptin: a promising therapeutic target with pleiotropic action besides body weight regulation. Curr Drug Targets 2006;7:761–771.
- Holzer P: Role of visceral afferent neurons in mucosal inflammation and defense. Curr Opin Pharmacol 2007;7:563–569.
- Turina M, Miller FN, Tucker C, Polk HC: Effects of hyperglycemia, hyperinsulinemia, and hyperosmolarity on neutrophil apoptosis. Surg Infect (Larchmt) 2006;7:111–121.
- Milak MS, Shimansky Y, Bracha V, Bloedel JR: Effects of inactivating individual cerebellar nuclei on the performance and retention of an operantly conditioned forelimb movement. J Neurophysiol 1997;78:939–959.
- Martin JH, Cooper SE, Hacking A, Ghez C: Differential effects of deep cerebellar nuclei inactivation on reaching and adaptive control. J Neurophysiol 2000;83:1886–1899.
Article / Publication Details
Copyright / Drug Dosage / DisclaimerCopyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.