Activation of Neurons in the Rat Medulla Following a Gag Reflex Stimulus

Authors

  • Donna Scarborough Department of Speech Pathology and Audiology, Miami University, Oxford, OH 45056, USA
  • Lori Isaacson Department of Biology, Center for Neuroscience and Behavior, Miami University, Oxford, OH 45056, USA

DOI:

https://doi.org/10.12970/2311-1917.2014.02.01.2

Keywords:

 Brain stem, Nucleus of the solitary tract, neuroanatomy, animal model, pediatric feeding.

Abstract

Despite the fact that a number of individuals present with a hypersensitive gag reflex, research in this area has been limited to clinical applications. An animal model that describes the neurologic underpinnings of the gag reflex has not been reported. Thus, the objective of the current study was to localize activated neurons in the rat medulla and to investigate their neurochemistry following mechanostimulation to the posterior pharyngeal wall eliciting a gag reflex response. Activated neurons, determined using c-fos immunohistochemistry, were observed in subnuclei of the nucleus tractus solitarius (NTS) and motor regions such as dorsal motor vagus, hypoglossal, and nucleus ambiguus. The lateral and dorsal paragigantocellular nuclei and the medial rostral ventrolateral nucleus involved in bitter taste processing, also showed robust activation. Tyrosine hydroxylase and/or choline acetyltransferase immunoreactivity was localized in many activated neurons. The results of the present study provide the first documentation of activated neurons and preliminary neurochemistry in brainstem nuclei that are unique to mechanostimulation to the posterior pharyngeal wall. Our results support postulated medullary structures involved with the gag reflex and propose new regions to be added to the circuitry model. Further, our results reveal an activation pattern within the NTS unique to the gag reflex.

References

Miller AJ. Oral and pharyngeal reflexes in the mammalian nervous system: Their diverse range in complexity and the pivotal role of the tongue. Crit Rev Oral Biol Med 2002; 13: 409-25. http://dx.doi.org/10.1177/154411130201300505

Martin JH. Neuroanatomy text and atlas. 2nd ed. Stamford (Conn): Appleton & Lange 1996; pp. 392-393.

Nolte J. The human brain, 3rd ed. St. Louis: Mosby-Year Book 1993; pp. 198-199.

Schulze-Delrieu K, Miller RM. Clinical Assessment of Dysphagia. In: Perlman AL, Schulze-Delrieu K, Eds. Deglutition and its disorders: anatomy, physiology, clinical diagnoses, and management. San Diego: Singular Publishing Group 1983; 144-5.

Scarborough DR, Van Kuren M, Hughes M. Altering the gag reflex via a hand pressure point. J Am Dent Assoc 2008; 139: 1365-72. http://dx.doi.org/10.14219/jada.archive.2008.0048

Akarslan ZZ, Bicer AZY. Utility of the gagging problem assessment questionnaire in assessing patient sensitivity to dental treatments. J Oral Rehabil 2012; 39: 948-55. http://dx.doi.org/10.1111/j.1365-2842.2012.02321.x

Bassi GS, Humphris GM, Longman LP. The etiology and management of gagging: a review of the literature. J Prosthet Dent 2004; 91: 459-67. http://dx.doi.org/10.1016/j.prosdent.2004.02.018

Leder SB. Gag reflex and dysphagia. Head Neck 1996; 18: 138-41. http://dx.doi.org/10.1002/(SICI)1097- 0347(199603/04)18:23.0.CO;2-2

Perlman AL, Luschei ES, Du Mond CE. Electrical activity from the superior pharyngeal constrictor during reflexive and non-reflexive tasks. J Speech Lang Hear Res 1989; 32: 749- 52.

Saita N, Fukuda K, Koukita Y, Ichinohe T, Yamashita S. Relationship between gagging severity and its management in dentistry. J Oral Rehabil 2013; 40: 106-11. http://dx.doi.org/10.1111/joor.12014

Byars KC, Burklow KA, Ferguson K, O’Flaherty T, Santoro K, Kaul A. A multi-component behavioral program for oral aversion in children dependent upon gastrostomy feedings. J Pediatr Gastroenterol Nutr 2003; 37: 473-80. http://dx.doi.org/10.1097/00005176-200310000-00014

Scarborough DR, Boyce S, McCain G, Oppenheimer S, August A, Neils-Strinjas J. Abnormal physiological responses among children with persistent feeding difficulties. Dev Med Child Neurol 2006; 48: 460-64. http://dx.doi.org/10.1017/S0012162206000995

Armfield JM. Towards a better understanding of dental axiety and fear: cognitions vs. experiences. Eur J Oral Sci 2010; 118: 259-64. http://dx.doi.org/10.1111/j.1600-0722.2010.00740.x

Scarborough DR, Isaacson LG. Hypothetical anatomical model to describe the aberrant gag reflex observed in a clinical population of orally deprived children. Clin Anat 2006; 19: 640-44. http://dx.doi.org/10.1002/ca.20301

Rogers RC, Travagli RA, Hermann GE. Noradrenergic neurons in the rat solitary nucleus participate in the esophageal-gastric relaxation reflex. AJ Physiol Regul Integr Comp Physiol 2003; 285: R479-89.

Paxinos G, Watson C. The rat brain: In stereotaxic coordinates. 4th ed. San Diego: Academic Press 1998.

Takemura M, Wakisaka S, Iwase K, et al. NADPH diaphorase in the developing rat: lower brainstem and cervical spinal cord, with special reference to the trigemino solitary complex. J Comp Neurol 1996; 365: 511-25. http://dx.doi.org/10.1002/(SICI)1096- 9861(19960219)365:43.0.CO;2-7

Roozendaal B, Williams CL, McGaugh JL. Glucocorticoid receptor activation in the rat nucleus of the solitary tract facilitates memory consolidation: involvement of the basolateral amygdala. Eur J Neurosci 1999; 11: 1317-23. http://dx.doi.org/10.1046/j.1460-9568.1999.00537.x

Brining SK, Smith DV. Distribution and synaptology of glossopharyngeal afferent nerve terminals in the nucleus of the solitary tract of the hamster. J Comp Neurol 1996; 365: 556-74. http://dx.doi.org/10.1002/(SICI)1096- 9861(19960219)365:43.0.CO;2-3

Kalia M, Sullivan JM. Brainstem projections of sensory and motor components of the vagus nerve in the rat. J Comp Neurol 1982; 211: 248-64. http://dx.doi.org/10.1002/cne.902110304

Hayakawa T, Maeda S, Tanaka K, Seki M. Fine structural survey of the intermediate subnuclues of the nucleus tractus solitarii and its glossopharyngeal afferent terminals. Anat Histol Embryol 2005; 210: 235-44. http://dx.doi.org/10.1007/s00429-005-0021-9

Kramer RB, Braham RL. The management of the chronic or hysterical gagger. ASDC 1977; 44: 111-6.

Murphy WM: A clinical survey of gagging patients. J Prostet Dent 1979; 42: 145-8. http://dx.doi.org/10.1016/0022-3913(79)90163-X

Denardo LA, Travers JB. Distribution of fos-like immunoreactivity in the medullary reticular formation of the rat after gustatory elicited ingestion and rejection behaviors. J Neurosci 1997; 17: 3826-39.

Grill HJ, Norgren R. The taste reactivity test. I. Mimetic responses to gustatory stimuli in neurologically normal rats. Brain Res 1978; 143: 263-79. http://dx.doi.org/10.1016/0006-8993(78)90568-1

Kinzeler NR, Travers S. Licking and gaping elicited by microstimulation of the nucleus of the solitary tract. Am J Physiol Regul Integr Comp Physiol 2008; 295: R436-48. http://dx.doi.org/10.1152/ajpregu.00189.2008

Yokota S, Tsumori T, Oka T, Nakamura S, Yasui Y. GABAergic neurons in the ventrolateral subnucleus of the nucleus tractus solitarius are in contact with Kolliker-Fuse nucleus projecting to the rostral ventral respiratory group and phrenic nucleus in the rat. Brain Res 2008; 1228: 113-26. http://dx.doi.org/10.1016/j.brainres.2008.06.089

Zhang X, Fogel R, Renehan WE. Relationship between the morphology and function of gastric and intestine-sensitive neurons in the nucleus of the solitary tract. J Comp Neurol 1995; 363: 37-52. http://dx.doi.org/10.1002/cne.903630105

Travers SP, Norgren K. Organization of orosensory responses in the nucleus of the solitary tract of rat. J Neurophysiol 1995; 73: 2144-62.

Lee A, Wissekerke AE, Rosin DL, Lynch KR. Location of 2c - adrenergic receptor immunoreactivity in catecholaminergic neurons in the rat central nervous system. Neuroscience 1998; 84: 1085-96. http://dx.doi.org/10.1016/S0306-4522(97)00578-2

Zhul L, Onaka T. Involvement of medullary A2 noradrenergic neurons in the activation of oxytocin neurons after conditioned fear stimuli. Eur J Neuroscience 2002; 16: 2186- 98. http://dx.doi.org/10.1046/j.1460-9568.2002.02285.x

Appleyard SM, Marks D, Kobayashi K, Okano H, Low MJ, Andresen MC. Visceral afferents directly activate catecholamine neurons in the solitary tract nucleus. J Neurosci 2007; 27: 13292-302. http://dx.doi.org/10.1523/JNEUROSCI.3502-07.2007

Cone RD. Anatomy and regulation of the central melanocortin system. Nat Neurosci 2005; 8: 571-8. http://dx.doi.org/10.1038/nn1455

Cone RD. Studies on the physiological functions of the melanocortin system. Endocr Rev 2006; 27: 736-49. http://dx.doi.org/10.1210/er.2006-0034

Hornby PJ. Central neurocircuitry associated with emesis. Am J Med 2001; 111: 106S-12.

Jean A. Brainstem organization of the swallowing network. Brain Behav Evol 1984; 25: 109-16. http://dx.doi.org/10.1159/000118856

Borinson H, Borinson R, McCarthy LE. Phylogenic and neurological aspects of the vomiting process. J Clin Pharmacol 1981; 21: 23S-9.

Uchino M, Kuwahara M, Ebukuro S, Tsubone H. Modulation of emetic response by carotid baro- and chemoreceptor activations. Auton Neurosci 2006; 128: 25-36. http://dx.doi.org/10.1016/j.autneu.2005.12.006

Zhang L-L, Ashwell KWS. Development of the cyto- and chemoarchitecutral organization of the rat nucleus of the solitary tract. Anat Histol Embryol 2001; 203: 265-82. http://dx.doi.org/10.1007/s004290000151

VanderHorst VGJM, Ulfhake B. The organization of the brainstem and spinal cord of the mouse: Relationships between monoaminergic, cholinergic, and spinal projection systems. J Chem Neuroanat 2006; 31: 2-36. http://dx.doi.org/10.1016/j.jchemneu.2005.08.003

Downloads

Published

2014-04-05

Issue

Section

Articles