Opiate peptides, interacting with m opiate receptors (MORs), affect food intake. One explanation for the basis of these effects is that they influence food palatability. Forebrain structures, especially nucleus accumbens and the ventral pallidum, comprise a critical substrate for the effect of MORs on feeding. Nevertheless, endorphins also impact eating through brainstem circuits, although the loci, effects, and mechanisms of these influences are less clear. One candidate brainstem region includes taste neurons in the rostral nucleus of the solitary tract (rNST) and oromotor circuitry in subjacent reticular formation (RF), a functionally-integrated region that we call the """"""""rostral solitary complex"""""""" (RSC). Previous studies suggest that injecting MOR agonists into this vicinity increases food intake whereas antagonists have the opposite effect. Preliminary data with more precise injections and behavioral measures, however, instead suggest that MOR agonist infusions into the RSC exert multiple influences, including immediate effects more indicative of a suppression of feeding. We hypothesize that these complex effects reflect the interaction of these ligands at multiple points in this heterogeneous circuitry. The goal of the present proposal is to precisely define the behavioral consequences of manipulating MORs in the rNST and subjacent RF and to specify the sites and cellular basis of these effects.
The Specific Aims are to: (1) Analyze the sensory and motor consequences of manipulating MORs in the rNST and subjacent RF by making small (60nl) infusions of MOR agonists (DAMGO) and antagonists (CTOP), and using multiple behavioral measures, including taste reactivity and short-term taste preference tests. (2) Establish the impact of local injections of DAMGO and CTOP on single-unit gustatory and oral somatosensory responses in the rNST and RF in an in vivo preparation, and (3) Perform in vitro, patch-clamp recordings from the rNST and subjacent RF to characterize the cellular basis of MOR modulation of neurons identified by their afferent and efferent connectivity. Previous work, including studies completed during the last project period, has clarified neurophysiological response properties and connectivity of brainstem taste neurons but knowledge about neurotransmitter function in central taste circuits is scarce. The proposed experiments will begin to fill this void. Moreover, these studies will contribute to understanding of the neural control of feeding, a behavior profoundly impacting human health. The neural substrate regulating eating is complex, involving interactions between multiple regions and levels of the central nervous system. Taste has a major influence on this behavior and the rNST is the 1st central site where these sensory signals are processed. The underlying RF contains motor circuitry comprising a final common pathway that integrates forebrain and hindbrain signals determining whether food intake continues or is aborted. The goal of this proposal is to understand how one class of neuromodulators important in feeding, m opiate ligands, interact at these critical nodes.

Public Health Relevance

The rostral portion of the nucleus of the solitary tract is the initial termination site of all primary afferent fibers conveying gustatory information. Good nutrition is critical to health, and the sense of taste profoundly impacts the type and amount of food eaten. This project will focus on how one class of opiate peptides known to promote eating, influences this region of the brain.

Agency
National Institute of Health (NIH)
Institute
National Institute on Deafness and Other Communication Disorders (NIDCD)
Type
Research Project (R01)
Project #
5R01DC000416-23
Application #
8523186
Study Section
Somatosensory and Chemosensory Systems Study Section (SCS)
Program Officer
Sullivan, Susan L
Project Start
1986-09-01
Project End
2014-08-31
Budget Start
2013-09-01
Budget End
2014-08-31
Support Year
23
Fiscal Year
2013
Total Cost
$295,027
Indirect Cost
$101,567
Name
Ohio State University
Department
Dentistry
Type
Schools of Dentistry
DUNS #
832127323
City
Columbus
State
OH
Country
United States
Zip Code
43210
Travers, Susan; Breza, Joseph; Harley, Jacob et al. (2018) Neurons with diverse phenotypes project from the caudal to the rostral nucleus of the solitary tract. J Comp Neurol 526:2319-2338
Spector, Alan C; le Roux, Carel W; Munger, Steven D et al. (2017) Proceedings of the 2015 ASPEN Research Workshop-Taste Signaling. JPEN J Parenter Enteral Nutr 41:113-124
Chen, Z; Travers, S P; Travers, J B (2016) Inhibitory modulation of optogenetically identified neuron subtypes in the rostral solitary nucleus. J Neurophysiol 116:391-403
Boxwell, A J; Chen, Z; Mathes, C M et al. (2015) Effects of high-fat diet and gastric bypass on neurons in the caudal solitary nucleus. Physiol Behav 152:329-39
Nasse, Jason S (2014) A novel slice preparation to study medullary oromotor and autonomic circuits in vitro. J Neurosci Methods 237:41-53
Nasse, Jason S; Travers, Joseph B (2014) Adrenoreceptor modulation of oromotor pathways in the rat medulla. J Neurophysiol 112:580-93
Boxwell, Alison J; Yanagawa, Yuchio; Travers, Susan P et al. (2013) The ?-opioid receptor agonist DAMGO presynaptically suppresses solitary tract-evoked input to neurons in the rostral solitary nucleus. J Neurophysiol 109:2815-26
Chen, Zhixiong; Travers, Susan P; Travers, Joseph B (2012) Activation of NPY receptors suppresses excitatory synaptic transmission in a taste-feeding network in the lower brain stem. Am J Physiol Regul Integr Comp Physiol 302:R1401-10
Kinzeler, Nicole R; Travers, Susan P (2011) ýý-Opioid modulation in the rostral solitary nucleus and reticular formation alters taste reactivity: evidence for a suppressive effect on consummatory behavior. Am J Physiol Regul Integr Comp Physiol 301:R690-700
Geran, Laura C; Travers, Susan P (2011) Glossopharyngeal nerve transection impairs unconditioned avoidance of diverse bitter stimuli in rats. Behav Neurosci 125:519-28

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