Journal of Vestibular Research 14 (2004) 95-294 95 IOS Press

Abstracts currently unclear as to how the vestibular system can modulate energy metabolism, both altered autonomic and O001 neuroendocrine outflow are implicated. Vestibular Function Revisited: Influence on Physiologi- cal Homeostasis C. A. Fuller O002 Neurobiology, Physiology & Behavior, University of Cali- The Role of the Vestibular System in Respiratory Regu- fornia, Davis, United States lation B. J. Yates1, I. Billig1, L. Cotter1, A. Anker2, T. Shintani3, Background: Previous work by our laboratory as well as K. Wilkinson2 others has demonstrated that gravity influences the regula- 1Otolaryngology, 2Neuroscience, University of Pittsburgh, tion of body mass, body composition, intermediary metabo- Pittsburgh, United States, 3Otolaryngology, St. Marianna lism and energy metabolism. More recent work by our University School of Medicine, Kawasaki, Japan laboratory has suggested that the vestibular system may largely mediate this gravitational influence on the physio- Background: Changes in posture can affect the resting logical regulation of energetics and metabolism. Data sup- length of respiratory pump muscles, requiring alterations in porting this vestibular-metabolism interrelationship in- the activity of these muscles if ventilation is to be unaf- cludes the observations that mice lacking macular gravity fected. For example, nose-up tilt of quadrupeds or standing reception demonstrate different food intake, body mass and in humans from a supine position can produce diaphragm composition responses to long-term increases in gravity shortening. The activity of some upper airway muscles also (+G). increases during certain postural alterations. This increase Objectives: The objective of these studies has been to elu- in activity is most evident when humans assume a supine cidate the role of the vestibular system in the regulation of position or quadrupeds are tilted nose-up, because under physiological homeostasis. these conditions the tongue tends to shift to the back of the Methods: We have generated our observations by utilizing throat and may obstruct the airway. In particular, the surgical and chemical bilaterally labyrinthectomized rats tongue protruder muscle genioglossus must be more active (Labx), as well as recombinant and mutant mouse vestibu- during these postural changes in order to maintain airway lar animal models, to ascertain the influence of vestibular patency. inputs on physiological homeostasis, including food intake, Objectives: The results from four groups of experiments body mass and composition, temperature regulation, activ- will be discussed, which indicate the following: 1) stimula- ity and plasma leptin at normal Earth gravity (1G). tion of vestibular receptors alters the activity of respiratory Results: Thus far, we have consistently observed a signifi- muscles; 2) bilateral labyrinthectomy alters the responses cant decrease in body mass, adiposity, and plasma leptin in of respiratory muscles during postural alterations; 3) the Labx animals as compared to Sham-operated (sham) con- medial medullary reticular formation (MRF) participates in trols. The lower body mass in the Labx animals appears to relaying vestibular signals to respiratory motoneurons. be a ‘regulated’ phenomenon. We conclude this based on Methods: In the first experiment, electrodes were surgi- our observation that fasted Labx animals, upon re- cally placed on the round window of felines for stimulating alimentation, recover lost body mass as quickly as their vestibular afferents, and the effects of this stimulation on Sham counterparts, suggested nutrient uptake and assimila- activity of the respiratory pump muscles and the airway tion is not compromised in Labx animals. In addition, body muscle genioglossus were recorded while the animals were composition analysis suggests that this loss of body mass is conscious. In the second experiment, the effects of a bilat- almost entirely attributable to a selective loss of carcass fat. eral labyrinthectomy on the background activity and re- Consistent with the loss of carcass fat is a corresponding sponses to nose-up and ear-down tilts of respiratory mus- decrease in plasma leptin levels. Somewhat paradoxically, cles were ascertained. In a third experiment, a neural tracer mass-independent food intake is elevated in the Labx ani- (pseudorabies virus) that was transported retrogradely mals as compared with Sham controls. In contrast to body across synapses was used to determine pathways that may mass, body composition and leptin, neither body tempera- relay vestibular signals to respiratory motoneurons. As ture nor locomotor activity levels were significantly differ- noted below, these experiments revealed that the MRF ent between the Labx and Sham groups. Finally, using c- likely participates in generating vestibulo-respiratory re- Fos immunoreactivity, we have confirmed vestibular sponses. In a fourth experiment, we recorded from MRF modulation of hypothalamic centers involved in physio- neurons whose axons could be stimulated from the vicinity logical homeostasis, including energy balance. of diaphragm motoneurons, and determined whether these Conclusion: Collectively, the data suggests that the vesti- cells received vestibular inputs. bular system can influence energy metabolism, though Results: Electrical stimulation of the labyrinth produced direct calorimetery will be needed to confirm this. Though short latency changes in activity of the diaphragm, abdomi- nal muscles, and genioglossus. Changes in muscle activity were also elicited by nose-up tilts of the whole body, but

0957-4271/04/$17.00 © 2004 – IOS Press and the authors. All rights reserved

96 Abstracts: Bárány Society XXIII International Congress these responses were significantly altered by a bilateral the otolith inputs and thus reduce or eliminate these adap- labyrinthectomy. Anatomical studies revealed that in addi- tive mechanisms. Further work is necessary to examine the tion to neurons located in the brainstem "respiratory cen- role of otolith inputs in orthostatic intolerance. This work ter," cells in the MRF provide inputs to respiratory moto- was supported by the NIA, NIDCD and NASA. neurons. Recordings from MRF units whose axons were References: antidromically activated from the vicinity of diaphragm [1] Serrador J.M., Shoemaker J.K., Brown T.E., Kas- motoneurons confirmed that some of these cells received sam M.S., Bondar R.L., and Schlegel T.T. Cerebral labyrinthine inputs. vasoconstriction precedes orthostatic intolerance af- Conclusion: The present results show that the vestibular ter parabolic flight. Brain Res Bull 53: 113-120, system participates in regulating the activity of respiratory 2000. muscles during movement and changes in posture. These [2] Serrador J.M., Wood S.J., Picot P.A., Stein F., Kas- vestibulo-respiratory responses are mediated in part by sam M.S., Bondar R.L., Rupert A.H., and Schlegel neurons in the MRF. T.T. Effect of acute exposure to hypergravity (GX Supported by the National Institutes of Health of the USA, vs. GZ) on dynamic cerebral autoregulation. J App grant R01-DC03732. Physiol 91: 1986-1994., 2001. [3] Wilson T.D., Serrador J.M., and Shoemaker J.K. Head position modifies cerebrovascular response to O003 orthostatic stress. Brain Res 961: 261-268., 2003. Vestibular Effects on Cerebral Blood Flow Regulation [4] Yates B.J. and Miller A.D. Physiological evidence J. M. Serrador that the vestibular system participates in autonomic Division on Aging, Harvard Medical School, Boston, and respiratory control. J Vestib Res 8: 17-25., United States 1998. Background: Previous research has demonstrated an im- portant role for the vestibular system in autonomic regula- O004 tion [4]. However, it remains unclear what role the vestibu- Labyrinthectomy Decreases Bone Mineral Density in lar system plays in regulation of cerebral blood flow. We the Femoral Metaphysis in Rats have previously found that subjects that become motion P. Denise1, O. Etard1, J. Sabatier2, J. Corvisier1, C.