Comprehensive Physiology Wiley Online Library

Central nervous system mechanisms in deglutition and emesis

Full Article on Wiley Online Library



Abstract

The sections in this article are:

1 Deglutition
1.1 Sensory Components of Deglutition
1.2 Central Sensory Representation of Deglutition
1.3 Motor Mechanisms of Deglutition
1.4 Swallowing Center or Central Pattern Generator for Deglutition
2 Emesis
2.1 Neural Circuitry for Emesis
2.2 Structure of Area Postrema
2.3 Transmitter Localization and Binding Sites in Area Postrema
2.4 Physiology of Area Postrema
2.5 Vomiting Center or Central Pattern Generator for Emesis
2.6 Motion and Space Sickness
2.7 Radiation‐Induced Emesis
2.8 Chemotherapy‐Induced Emesis
2.9 Other Forms of Emesis
2.10 Pharmacology of Emesis
3 Conclusion
Figure 1. Figure 1.

Sensory and motor nuclei of brain stem involved in mastication and swallowing. Sensory nuclei are shown only on right and motor nuclei only on left. Nuclei are associated with cranial neuron(s) [N (Nn)] V, VII, IX, X, IX, and XII.

From Sessle
Figure 2. Figure 2.

Potential proprioceptive and exteroceptive sensory inputs from anatomical regions during swallowing. Innervation of particular muscles, joints, and mucosal regions and central projections of primary afferent fibers are based on previous anatomical and physiological studies. Sensory input from stylohyoid muscle, innervated by facial nerve, is not shown.

Adapted from Miller
Figure 3. Figure 3.

Rhythmic swallowing induced by superior laryngeal nerve (SLN) stimulation (A) and by solitary tract stimulation (B). EMG, electromyographic activity of suprahyoid muscles; P, intrapharyngeal pressure; St, stimulation (trains of pulses 0.5 V, 0.3 ms, 30 Hz in both A and B. Characteristics of swallowing elicited by central stimulation are very similar to those of swallowing elicited by SLN stimulation

From Kessler and Jean
Figure 4. Figure 4.

Location of medullary regions whose stimulation induced swallowing. Each drawing from the atlas by Pellegrino et al. represents a coronal hemisection of the rat medulla. Numbers indicate the rostrocaudal position (interaural line as reference). Filled circles, location of the active points. NA, nucleus ambiguus; NTS, nucleus of solitary tract; ST, stria terminalis; nsTV, nucleus of spinal tract of trigeminal nerve; RF, retrofacial nucleus; sTV, spinal tract of the trigeminal nerve; X, dorsal motor nucleus of vagus nerve; XII, motor nucleus of hypoglossal nerve.

From Kessler and Jean
Figure 5. Figure 5.

Evoked field potential and neuronal responses recorded in 5 microelectrode penetrations in cat caudal brain stem. Penetrations (a‐e) were made in 0.5‐mm steps mediolaterally in 1 anteroposterior plane (2 mm anterior to obex) and are indicated in transverse section. Right, field potentials evoked by superior laryngeal nerve (SLN) and glossopharyngeal nerve (IX) stimulation and recorded at various depths (broken arrows) of penetration (c) through solitary tract and its nucleus (outlined) and reticular formation ventral to it (vertical depth measurements were determined from readings of electrode microdrive with allowance of 20% for tissue shrinkage). Single units recorded in the 5 penetrations are indicated by various symbols on transverse section. Bottom, typical responses to SLN stimulation of solitary tract primary fiber (open circle) at 200/s stimulation rate, solitary tract neuron (filled circle), and neuron located in adjacent reticular formation. Filled triangle, neuron projecting to the rostral brain stem; open triangle, reticular formation neuron that could not be antidromically activated from this region. Also illustrated is response to infraorbital nerve (IO) stimulation of reticular formation neuron (V) with only demonstrated IO input. Negative polarity is upward; voltage calibration, 0.4 m V; time calibration, 4 ms for all records except solitary tract fiber and neuron for which it is 2 ms. V, nucleus of spinal tract of trigeminal nerve, with the tract lateral to it; X, dorsal motor nucleus of vagus nerve; XII, hypoglossal motor nucleus.

From Sessle
Figure 6. Figure 6.

Organization of superior laryngeal nerve (SLN) central projections involved in reflex and cortical control of bulbar swallowing center. Continuous line, SLN projections with ascending path terminating in frontal swallowing cortex and the descending path reaching nucleus tractus solitarius ˜3 mm in front of obex (part of bulbar swallowing center). Latency of evoked potentials at different levels is indicated in parentheses. Discontinuous line, origin of corticofugal swallowing pathway and its bulbar termination. LME, lamina medullaris externa; P Cer, pedunculus cerebri, TO, tractus opticus; VPM, nucleus ventroposteromedialis; PSV, nucleus principalis sensibilis nucleus trigemini; MV, nucleus motorius nucleus trigemini; Tsp V tractus spinalis nucleus trigemini; FRP, formatio reticularis pontis; NOS, nucleus olivaris superior; NTspV, nucleus tractus spinalis nucleus trigemini; NA, nucleus ambiguus; NRgc, nucleus reticularis gigantocellularis; NRpc, nucleus reticularis parvocellularis.

From Car et al.
Figure 7. Figure 7.

Basal ganglionic and limbic forebrain circuits likely to participate in supranuclear control of swallowing. BST, bed nucleus of stria terminalis; X, cortex; FR, fasciculus retroflexus; IPT, inferior thalamic peduncle; MFB, median forebrain bundle; SM, stria medullaris; ST, stria terminalis.

From Hockman et al. . © 1979, with permission from Pergamon Press, Ltd
Figure 8. Figure 8.

Motor output of swallowing reflex. Motor nuclei activated by their interneuronal system are indicated and muscles that contract during buccopharyngeal phase are shown in their anatomical region. Those muscles active during the first 0–40 ms of swallow are indicated by Roman numeral I.

Adapted from Miller
Figure 9. Figure 9.

Activity of rat swallowing neurons. EMG, electromyographic activity of suprahyoid muscles; N, neuronal activity, St, superior laryngeal nerve (SLN) stimulation. A and B: activity of 2 different neurons located at level of nucleus tractus solitarius (group I). In A 1 and B 1 stimulation of ipsilateral SLN [3 pulses at 500 Hz in A 1 (bar), 3 pulses at 30 Hz in B 1 (dots)] induced initial response with short latency followed by burst of spikes related to EMG activity (swallowing activity). Beginning of swallowing activity occurred before onset of EMG activity (A 1). In A 2 and B 2 note very short latency of initial response of these neurons elicited by ipsilateral SLN stimulation (single pulse indicated by dots). C and D: activity of group II neurons located at level of the nucleus ambiguus (C) or hypoglossal nucleus (D). C 1 and D 1: swallowing activity elicited by ipsilateral SLN stimulation (short trains of pulses at 30 Hz indicated by dots). C 2 and D 2: initial response of same neurons elicited by ipsilateral SLN stimulation with 2 pulses (dots) at 1,000 Hz in C 2 (3 superimposed sweeps) and 4 pulses (bar) at 1,000 Hz in D 2.

From Kessler and Jean
Figure 10. Figure 10.

Effect of motor paralysis on activity of rat swallowing neurons. A: recording from group I neuron located at level of nucleus tractus solitarius. B: recording from group II neuron located at level of hypoglossal nucleus. A 1 and B 1: control tracings before motor paralysis. A 2 and B 2: tracings after motor paralysis of animal performed by injection of gallamine triethiodide (2 mg/kg). Abbreviations as in Fig. . In A and B characteristics of neuronal discharges remained unaltered after motor paralysis.

From Kessler and Jean
Figure 11. Figure 11.

Afferent pathways for vomiting by agents acting at central and peripheral sites. TZ, chemoceptive emetic trigger zone; VC, vomiting center. Apomorphine, morphine, lanatoside C, hydergine, and intravenous (iv) copper sulfate act at TZ, whereas intragastric copper sulfate acts through gastric afferents that project directly to VC.

Adapted from Wang and Tyson
Figure 12. Figure 12.

Neurons of area postrema and adjacent structures as seen in Golgi or Golgi‐Cox preparations in transverse section through floor of the 4th ventricle. AP, area postrema; FLM, medial longitudinal fasciculus; IC, nucleus intercalatus; NG, nucleus gracilis; SN, nucleus tractus solitarius; ST, tractus solitarius; TST, tractus tectospinalis; X, dorsal motor vagal nucleus; XII, nucleus hypoglossus; a, emergent hypoglossal axon; b, axon from nucleus tractus solitarius entering reticular formation; c, dorsolateral fiber bundle of area postrema; f, axon of cell of nucleus tractus solitarius with dendrite protruding into area postrema; g, neuron of area postrema; h, intrinsic fiber plexus of area postrema.

From Morest
Figure 13. Figure 13.

Anterograde labeling (small dots) produced from rostral to caudal in dorsal pons (A, B) and medulla (C‐E) after injection restricted to area postrema of wheat germ agglutinin conjugated to horseradish peroxidase. AP, area postrema; BC, brachium conjunctivum; DTC, central dorsal tegmental nucleus; DTL, dorsolateral tegmental nucleus; DTP, pericentral dorsal tegmental nucleus; LC, locus coeruleus; MES V, mesencephalic trigeminal tract and nucleus; SENS V, principal sensory trigeminal nucleus; SL, lateral solitary nucleus; SMD, dorsal division of medial solitary nucleus; SMV, ventral division of medial solitary nucleus; ST, solitary tract; SZE, external solitary zone; SZI, internal solitary zone; X, dorsal motor nucleus of vagus; XII, hypoglossal motor nucleus.

From van der Kooy and Koda
Figure 14. Figure 14.

Responses of single neuron in dog area postrema to ionophoretic application of glutamate (Glu) and gastrin. Neuron was 543 μm from surface of area postrema, which in the dog extends at least 700 μm deep. Large vertical deflections are artifacts of ionophoretic pulses, whereas smaller deflections are neuronal action potentials. Glutamate was applied as single pulse of 50 nC. Gastrin was applied in 5 100‐nC pulses, of which only the last 2 are shown. Response to glutamate was 3–5 spikes with short latency, high frequency, and brief duration, whereas response to gastrin was of long latency, low frequency, and long duration.

From Carpenter et al.
Figure 15. Figure 15.

Responses of dog area postrema neuron 490 μm from surface to glutamate (Glu), thyrotropin‐releasing hormone (TRH), and norepinephrine (NE). Response to glutamate was over within 1 s and was of relatively high frequency. Discharge in response to TRH, applied between large artifacts at 2,000 nC, had a 6‐s latency, reached maximal frequency of <0.5 Hz only after ˜20 s, and lasted for 3.5 min. After 2 applications each of TRH and VIP, neuron remained spontaneously active. Under these circumstances, inhibition by NE at 100 nC could be seen; Glu response was unchanged but was followed by a pause in spontaneous activity. About 40% of area postrema neurons were excited by NE, 40% inhibited, and 20% unaffected.

From Carpenter et al.
Figure 16. Figure 16.

Schematic representation of central nervous system pathways involved in motion sickness.

From Wang and Chinn


Figure 1.

Sensory and motor nuclei of brain stem involved in mastication and swallowing. Sensory nuclei are shown only on right and motor nuclei only on left. Nuclei are associated with cranial neuron(s) [N (Nn)] V, VII, IX, X, IX, and XII.

From Sessle


Figure 2.

Potential proprioceptive and exteroceptive sensory inputs from anatomical regions during swallowing. Innervation of particular muscles, joints, and mucosal regions and central projections of primary afferent fibers are based on previous anatomical and physiological studies. Sensory input from stylohyoid muscle, innervated by facial nerve, is not shown.

Adapted from Miller


Figure 3.

Rhythmic swallowing induced by superior laryngeal nerve (SLN) stimulation (A) and by solitary tract stimulation (B). EMG, electromyographic activity of suprahyoid muscles; P, intrapharyngeal pressure; St, stimulation (trains of pulses 0.5 V, 0.3 ms, 30 Hz in both A and B. Characteristics of swallowing elicited by central stimulation are very similar to those of swallowing elicited by SLN stimulation

From Kessler and Jean


Figure 4.

Location of medullary regions whose stimulation induced swallowing. Each drawing from the atlas by Pellegrino et al. represents a coronal hemisection of the rat medulla. Numbers indicate the rostrocaudal position (interaural line as reference). Filled circles, location of the active points. NA, nucleus ambiguus; NTS, nucleus of solitary tract; ST, stria terminalis; nsTV, nucleus of spinal tract of trigeminal nerve; RF, retrofacial nucleus; sTV, spinal tract of the trigeminal nerve; X, dorsal motor nucleus of vagus nerve; XII, motor nucleus of hypoglossal nerve.

From Kessler and Jean


Figure 5.

Evoked field potential and neuronal responses recorded in 5 microelectrode penetrations in cat caudal brain stem. Penetrations (a‐e) were made in 0.5‐mm steps mediolaterally in 1 anteroposterior plane (2 mm anterior to obex) and are indicated in transverse section. Right, field potentials evoked by superior laryngeal nerve (SLN) and glossopharyngeal nerve (IX) stimulation and recorded at various depths (broken arrows) of penetration (c) through solitary tract and its nucleus (outlined) and reticular formation ventral to it (vertical depth measurements were determined from readings of electrode microdrive with allowance of 20% for tissue shrinkage). Single units recorded in the 5 penetrations are indicated by various symbols on transverse section. Bottom, typical responses to SLN stimulation of solitary tract primary fiber (open circle) at 200/s stimulation rate, solitary tract neuron (filled circle), and neuron located in adjacent reticular formation. Filled triangle, neuron projecting to the rostral brain stem; open triangle, reticular formation neuron that could not be antidromically activated from this region. Also illustrated is response to infraorbital nerve (IO) stimulation of reticular formation neuron (V) with only demonstrated IO input. Negative polarity is upward; voltage calibration, 0.4 m V; time calibration, 4 ms for all records except solitary tract fiber and neuron for which it is 2 ms. V, nucleus of spinal tract of trigeminal nerve, with the tract lateral to it; X, dorsal motor nucleus of vagus nerve; XII, hypoglossal motor nucleus.

From Sessle


Figure 6.

Organization of superior laryngeal nerve (SLN) central projections involved in reflex and cortical control of bulbar swallowing center. Continuous line, SLN projections with ascending path terminating in frontal swallowing cortex and the descending path reaching nucleus tractus solitarius ˜3 mm in front of obex (part of bulbar swallowing center). Latency of evoked potentials at different levels is indicated in parentheses. Discontinuous line, origin of corticofugal swallowing pathway and its bulbar termination. LME, lamina medullaris externa; P Cer, pedunculus cerebri, TO, tractus opticus; VPM, nucleus ventroposteromedialis; PSV, nucleus principalis sensibilis nucleus trigemini; MV, nucleus motorius nucleus trigemini; Tsp V tractus spinalis nucleus trigemini; FRP, formatio reticularis pontis; NOS, nucleus olivaris superior; NTspV, nucleus tractus spinalis nucleus trigemini; NA, nucleus ambiguus; NRgc, nucleus reticularis gigantocellularis; NRpc, nucleus reticularis parvocellularis.

From Car et al.


Figure 7.

Basal ganglionic and limbic forebrain circuits likely to participate in supranuclear control of swallowing. BST, bed nucleus of stria terminalis; X, cortex; FR, fasciculus retroflexus; IPT, inferior thalamic peduncle; MFB, median forebrain bundle; SM, stria medullaris; ST, stria terminalis.

From Hockman et al. . © 1979, with permission from Pergamon Press, Ltd


Figure 8.

Motor output of swallowing reflex. Motor nuclei activated by their interneuronal system are indicated and muscles that contract during buccopharyngeal phase are shown in their anatomical region. Those muscles active during the first 0–40 ms of swallow are indicated by Roman numeral I.

Adapted from Miller


Figure 9.

Activity of rat swallowing neurons. EMG, electromyographic activity of suprahyoid muscles; N, neuronal activity, St, superior laryngeal nerve (SLN) stimulation. A and B: activity of 2 different neurons located at level of nucleus tractus solitarius (group I). In A 1 and B 1 stimulation of ipsilateral SLN [3 pulses at 500 Hz in A 1 (bar), 3 pulses at 30 Hz in B 1 (dots)] induced initial response with short latency followed by burst of spikes related to EMG activity (swallowing activity). Beginning of swallowing activity occurred before onset of EMG activity (A 1). In A 2 and B 2 note very short latency of initial response of these neurons elicited by ipsilateral SLN stimulation (single pulse indicated by dots). C and D: activity of group II neurons located at level of the nucleus ambiguus (C) or hypoglossal nucleus (D). C 1 and D 1: swallowing activity elicited by ipsilateral SLN stimulation (short trains of pulses at 30 Hz indicated by dots). C 2 and D 2: initial response of same neurons elicited by ipsilateral SLN stimulation with 2 pulses (dots) at 1,000 Hz in C 2 (3 superimposed sweeps) and 4 pulses (bar) at 1,000 Hz in D 2.

From Kessler and Jean


Figure 10.

Effect of motor paralysis on activity of rat swallowing neurons. A: recording from group I neuron located at level of nucleus tractus solitarius. B: recording from group II neuron located at level of hypoglossal nucleus. A 1 and B 1: control tracings before motor paralysis. A 2 and B 2: tracings after motor paralysis of animal performed by injection of gallamine triethiodide (2 mg/kg). Abbreviations as in Fig. . In A and B characteristics of neuronal discharges remained unaltered after motor paralysis.

From Kessler and Jean


Figure 11.

Afferent pathways for vomiting by agents acting at central and peripheral sites. TZ, chemoceptive emetic trigger zone; VC, vomiting center. Apomorphine, morphine, lanatoside C, hydergine, and intravenous (iv) copper sulfate act at TZ, whereas intragastric copper sulfate acts through gastric afferents that project directly to VC.

Adapted from Wang and Tyson


Figure 12.

Neurons of area postrema and adjacent structures as seen in Golgi or Golgi‐Cox preparations in transverse section through floor of the 4th ventricle. AP, area postrema; FLM, medial longitudinal fasciculus; IC, nucleus intercalatus; NG, nucleus gracilis; SN, nucleus tractus solitarius; ST, tractus solitarius; TST, tractus tectospinalis; X, dorsal motor vagal nucleus; XII, nucleus hypoglossus; a, emergent hypoglossal axon; b, axon from nucleus tractus solitarius entering reticular formation; c, dorsolateral fiber bundle of area postrema; f, axon of cell of nucleus tractus solitarius with dendrite protruding into area postrema; g, neuron of area postrema; h, intrinsic fiber plexus of area postrema.

From Morest


Figure 13.

Anterograde labeling (small dots) produced from rostral to caudal in dorsal pons (A, B) and medulla (C‐E) after injection restricted to area postrema of wheat germ agglutinin conjugated to horseradish peroxidase. AP, area postrema; BC, brachium conjunctivum; DTC, central dorsal tegmental nucleus; DTL, dorsolateral tegmental nucleus; DTP, pericentral dorsal tegmental nucleus; LC, locus coeruleus; MES V, mesencephalic trigeminal tract and nucleus; SENS V, principal sensory trigeminal nucleus; SL, lateral solitary nucleus; SMD, dorsal division of medial solitary nucleus; SMV, ventral division of medial solitary nucleus; ST, solitary tract; SZE, external solitary zone; SZI, internal solitary zone; X, dorsal motor nucleus of vagus; XII, hypoglossal motor nucleus.

From van der Kooy and Koda


Figure 14.

Responses of single neuron in dog area postrema to ionophoretic application of glutamate (Glu) and gastrin. Neuron was 543 μm from surface of area postrema, which in the dog extends at least 700 μm deep. Large vertical deflections are artifacts of ionophoretic pulses, whereas smaller deflections are neuronal action potentials. Glutamate was applied as single pulse of 50 nC. Gastrin was applied in 5 100‐nC pulses, of which only the last 2 are shown. Response to glutamate was 3–5 spikes with short latency, high frequency, and brief duration, whereas response to gastrin was of long latency, low frequency, and long duration.

From Carpenter et al.


Figure 15.

Responses of dog area postrema neuron 490 μm from surface to glutamate (Glu), thyrotropin‐releasing hormone (TRH), and norepinephrine (NE). Response to glutamate was over within 1 s and was of relatively high frequency. Discharge in response to TRH, applied between large artifacts at 2,000 nC, had a 6‐s latency, reached maximal frequency of <0.5 Hz only after ˜20 s, and lasted for 3.5 min. After 2 applications each of TRH and VIP, neuron remained spontaneously active. Under these circumstances, inhibition by NE at 100 nC could be seen; Glu response was unchanged but was followed by a pause in spontaneous activity. About 40% of area postrema neurons were excited by NE, 40% inhibited, and 20% unaffected.

From Carpenter et al.


Figure 16.

Schematic representation of central nervous system pathways involved in motion sickness.

From Wang and Chinn
References
 1. Adachi, A., and M. Kobashi. Chemosensitive neurons within the area postrema of the rat. Neurosci. Lett. 55: 137–140, 1985.
 2. Amri, M., and A. Car. Etude des neurones déglutiteurs pontiques chez la brebis. II. Effets de la stimulation des afférences périphéreques et du cortex fronto‐orbitaire. Exp. Brain Res. 48: 345–354, 1982.
 3. Armstrong, D. M., R. J. Miller, A. Beaudet, and V. M. Pickel. Enkephalin‐like immunoreactivity in rat area postrema: ultrastructural localization and co‐existence with serotonin. Brain Res. 310: 269–278, 1984.
 4. Armstrong, D. M., V. M. Pickel, T. H. Joh, and D. J. Reis. Electron microscopic immunocytochemical localization of tyrosine hydroxylase in the area postrema of rat. J. Comp. Neurol. 206: 259–272, 1982.
 5. Armstrong, D. M., V. M. Pickel, T. H. Joh, D. J. Reis, and R. J. Miller. Immunocytochemical localization of catecholamine synthesizing enzymes and neuropeptides in area postrema and medial nucleus tractus solitarius of rat brain. J. Comp. Neurol. 196: 505–517, 1981.
 6. Armstrong, D. M., V. M. Pickel, and D. J. Reis. Electron microscope immunocytochemical localization of substance P in the area postrema of rat. Brain Res. 243: 141–146, 1982.
 7. Bakowski, M. T. Advances in anti‐emetic therapy. Cancer Treat. Rev. 11: 237–256, 1984.
 8. Bard, P., C. N. Woolsey, R. S. Snider, V. B. Mountcastle, and R. B. Bromiley. Delimitation of central nervous mechanisms involved in motion sickness (Abstract). Federation Proc. 6: 72, 1947.
 9. Barnes, J. H. The physiology and pharmacology of emesis. Mol. Aspects Med. 7: 397–508, 1984.
 10. Barnes, K., C. Ferrario, and J. Conomy. Comparison of the hemodynamic changes produced by electrical stimulation of the area postrema and nucleus tractus solitarii in the dog. Circ. Res. 45: 136–143, 1979.
 11. Beckstead, R. M., and R. Norgren. An autoradiography examination of the central distribution of the trigeminal, facial, glossopharyngeal and vagal nerves in the monkey. J. Comp. Neurol. 184: 455–472, 1979.
 12. Berger, B. D., C. D. Wise, and L. Stein. Area postrema damage and bait shyness. J. Comp. Physiol. Psychol. 82: 475–479, 1973.
 13. Bhargava, K. P., and K. S. Dixit. Role of the chemoreceptor trigger zone in histamine‐induced emesis. Br. J. Pharmacol. 34: 508–513, 1968.
 14. Bhargava, K. P., K. S. Dixit, and Y. K. Gupta. Enkephalin receptors in the emetic chemoreceptor trigger zone of the dog. Br. J. Pharmacol. 72: 471–475, 1981.
 15. Bieger, D. Role of bulbar serotonergic neurotransmission in the initiation of swallowing in the rat. Neuropharmacology 20: 1073–1083, 1981.
 16. Bieger, D., and C. H. Hockman. Suprabulbar modulation of reflex swallowing. Exp. Neurol. 52: 311–324, 1976.
 17. Bieger, D., A. Weerasuriya, and C. H. Hockman. The emetic action of L‐dopa and its effect on the swallowing reflex in the cat. J. Neural Trans. 42: 87–98, 1978.
 18. Bird, E., C. C. Cardone, and R. J. Contreras. Area postrema lesions disrupt food intake induced by cerebroventricular infusions of 5‐thioglucose in the rat. Brain Res. 270: 193–196, 1983.
 19. Borison, H. L. Abdominal receptor site for emetic action of x‐irradiation. Federation Proc. 15: 21–22, 1956.
 20. Borison, H. L. Site of emetic action of x‐irradiation in the cat. J. Comp. Neurol. 107: 439–453, 1957.
 21. Borison, H. L. Effect of ablation of medullary emetic chemoreceptor trigger zone on vomiting responses to cerebral intraventricular injection of adrenaline, apomorphine and pilocarpine in the cat. J. Physiol. Lond. 147: 172–177, 1959.
 22. Borison, H. L. Area postrema: chemoreceptor trigger zone for vomiting—is that all? Life Sci. 14: 1807–1817, 1974.
 23. Borison, H. L. A misconception of motion sickness leads to false therapeutic expectations. Aviat. Space Environ. Med. 56: 66–68, 1985.
 24. Borison, H. L., R. Borison, and L. E. McCarthy. Phylogenic and neurologic aspects of the vomiting process. J. Clin. Pharmacol. 21: 235–295, 1981.
 25. Borison, H. L., E. D. Brand, and R. K. Orkand. Emetic action of nitrogen mustard (mechlorethamine hydrochloride) in dogs and cats. Am. J. Physiol. 192: 410–416, 1958.
 26. Borison, H. L., M. J. Hawken, J. I. Hubbard, and N. E. Sirett. Unit activity from the cat area postrema influenced by drugs. Brain Res. 92: 153–156, 1975.
 27. Borison, H. L., L. E. McCarthy, W. G. Clark, and N. Radhakrishnan. Vomiting, hypothermia and respiratory paralysis due to tetrodotoxin (puffer fish poison) in the cat. Toxicol. Appl. Pharmacol. 5: 350–357, 1963.
 28. Borison, H. L., and S. C. Wang. Functional localization of central coordinating mechanism for emesis in cat. J. Neurophysiol. 12: 305–313, 1949.
 29. Borison, H. L., and S. C. Wang. Quantitative effects of radon implanted in the medulla oblongata: a technique for producing discrete lesions. J. Comp. Neurol. 94: 33–56, 1951.
 30. Borison, H. L., and S. C. Wang. Physiology and pharmacology of vomiting. Pharmacol. Rev. 5: 193–230, 1953.
 31. Borison, R., and H. Borison. Postnatal development of the area postrema with relation to digitalis‐induced vomiting in the cat. Exp. Neurol. 40: 138–152, 1973.
 32. Borke, R. C., M. E. Nau, and R. L. Ringler. Brainstem afferents of hypoglossal neurons in the rat. Brain Res. 269: 47–55, 1983.
 33. Bosma, J. F. Deglutition: pharyngeal stage. Physiol. Rev. 37: 275–300, 1957.
 34. Brizzee, K. R. Effect of localized brain stem lesions and supradiaphragmatic vagotomy on x‐irradiation emesis in the monkey. Am. J. Physiol. 187: 567–570, 1956.
 35. Brizzee, K. R., F. M. Calton, and D. E. Vitale. Effects of selective placement of lesions in lower brain stem structures on x‐irradiation in the dog. Anat. Rec. 130: 533–541, 1958.
 36. Brizzee, K. R., and W. R. Mehler. The central nervous connections involved in the vomiting reflex. In: Nausea and Vomiting: Mechanisms and Treatment, edited by C. J. Davis, G. V. Lake‐Bakaar, and D. G. Grahame‐Smith. Heidelberg, FRG: Springer‐Verlag, 1986, p. 31–55.
 37. Brizzee, K. R., and L. M. Neal. A re‐evaluation of the cellular morphology of the area postrema in view of recent evidence for a chemoreceptor function. J. Comp. Neurol. 100: 41–61, 1954.
 38. Brizzee, K. R., J. M. Ordy, and W. R. Mehler. Effect of ablation of area postrema on frequency and latency of motion sickness‐induced emesis in the squirrel monkey. Physiol. Behav. 24: 849–853, 1980.
 39. Brooks, M. J., J. I. Hubbard, and N. E. Sirett. Extracellular recordings in rat area postrema in vitro and effects of cholinergic drugs, serotonin and angiotensin II. Brain. Res. 261: 85–90, 1983.
 40. Brownstein, M. J. Biologically active peptide in the mammalian central nervous system. In: Peptides in Neurobiology, edited by H. Gainer. New York: Plenum, 1977, p. 145–170.
 41. Cammermeyer, J. Mast cells in the mammalian area postrema. Z. Anat. Entwicklungsgesch. 139: 71–92, 1972.
 42. Car, A. La commande corticale du centre déglutiteur bulbaire. J. Physiol. Paris 62: 361–386, 1970.
 43. Car, A., and M. Amri. Etude des neurones déglutiteurs pontiques chez la brebis. I. Activité et localisation. Exp. Brain Res. 48: 345–354, 1982.
 44. Car, A., A. Jean, and C. Roman. A pontine primary relay for ascending projections of the superior laryngeal nerve. Exp. Brain Res. 22: 197–210, 1975.
 45. Car, A., and C. Roman. Déglutitions et contractions oesophagiennes réflexes produites par la stimulation du bulbe rachidien. Exp. Brain Res. 11: 75–92, 1970.
 46. Carpenter, D. O., D. B. Briggs, and N. Strominger. Responses of neurons of canine area postrema to neurotransmitters and peptides. Cell. Mol. Neurobiol. 3: 113–126, 1983.
 47. Carpenter, D. O., D. B. Briggs, and N. Strominger. Peptide‐induced emesis in dogs. Behav. Brain Res. 11: 277–281, 1984.
 48. Carpenter, D. O., D. B. Briggs, and N. Strominger. Behavioral and electrophysiological studies of peptide‐induced emesis in dogs. Federation Proc. 43: 16–18, 1984.
 49. Chernicky, C. L., K. L. Barnes, J. P. Conomy, and C. M. Ferrario. A morphological characterization of the canine area postrema. Neurosci. Lett. 20: 37–43, 1980.
 50. Chernicky, C. L., K. L. Barnes, C. M. Ferrario, and J. P. Conomy. Afferent projections of the cervical vagus and nodose ganglion in the dog. Brain Res. Bull. 13: 401–411, 1984.
 51. Chinn, H. I., and P. K. Smith. Motion sickness. Pharmacol. Rev. 7: 33–82, 1955.
 52. Chinn, H. I., and S. C. Wang. Locus of emetic action following irradiation. Proc. Soc. Exp. Biol. Med. 85: 472–474, 1954.
 53. Ciampini, G., and A. Jean. Role of des afférences glossopharyngiennes et trigéminales dans le déclenchement et le déroulement de la déglutition. Afférences glossopharyngiennes. J. Physiol. Paris 76: 61–66, 1980.
 54. Clarke, R. S. J. Nausea and vomiting. Br. J. Anaesth. 56: 19–27, 1984.
 55. Cleall, J. F. Deglutition: a study of form and function. Am. J. Orthod. 51: 566–594, 1965.
 56. Clemente, C. D., and V. L. van Breeman. Nerve fibers in the area postrema of cat, rabbit, guinea pig and rat. Anat. Rec. 123: 65–72, 1955.
 57. Cockel, R. Anti‐emetics. Practitioner 206: 56–63, 1971.
 58. Coil, J. D., W. G. Hankins, D. J. Jenden, and J. Garcia. The attenuation of a specific cue‐to‐consequence association by antiemetic agents. Psychopharmacology 56: 21–25, 1978.
 59. Conte, F. P., G. S. Melville, Jr., and A. C. Upton. Effects of graded doses of whole‐body x‐irradiation on mast cells in the rat mesentery. Am. J. Physiol. 187: 160–162, 1956.
 60. Cooper, J. R., and J. L. Mattsson. Control of radiation‐induced emesis with promethazine, cimetidine, thiethylperazine or naloxone. Am. J. Vet. Res. 40: 1057–1061, 1979.
 61. Costello, D. J., and H. L. Borison. Naloxone antagonizes narcotic self‐blockade of emesis in the cat. J. Pharmacol. Exp. Ther. 203: 222–230, 1977.
 62. Crampton, G. H., and N. G. Daunton. Evidence for a motion sickness agent in cerebrospinal fluid. Brain Behav. Evol. 23: 36–41, 1983.
 63. Cunningham, D. P., and J. V. Basmajian. Electromyography of genioglossus and geniohyoid muscles during deglutition. Anat. Rec. 165: 401–410, 1969.
 64. Cutz, E., Chan, W., N. S. Track, A. Goth, and S. I. Said. Release of vasoactive intestinal polypeptide in mast cells by histamine liberator. Nature Lond. 275: 661–662, 1978.
 65. Dahlström, A., and K. Fuxe. Evidence for the existence of monoamine‐containing neurons in the central nervous system. I. Demonstration of monoamines in the cell bodies of brain stem neurons. Acta Physiol. Scand. 62, Suppl. 232: 1–55, 1964.
 66. D'Amelio, F. E., M. Gibbs, W. R. Mehler, and L. F. Eng. Immunocytochemical localization of glial fibrillary acidic protein (GFAP) in the area postrema of the cat. Light and electron microscope study. Brain Res. 330: 146–149, 1985.
 67. Davies, R., and M. Kalia. Carotid sinus nerve projections to the brain stem in the cat. Brain Res. Bull. 6: 531–541, 1981.
 68. De Jong, W., P. Zandberg, M. Palkovits, and B. Bohus. Acute and chronic hypertension after lesion and transections of the rat brain stem. Prog. Brain Res. 47: 189–197, 1977.
 69. Dellow, P. C., and J. P. Lund. Evidence for central timing of rhythmical mastication. J. Physiol. Lond. 215: 11–13, 1971.
 70. Doty, R. W. Influence of stimulus pattern on reflex deglutition. Am. J. Physiol. 166: 142–158, 1951.
 71. Doty, R. W. An electromyographic analysis of reflex deglutition. J. Neurophysiol. 19: 44–60, 1956.
 72. Doty, R. W. Neural organization of deglutition. In: Handbook of Physiology. Alimentary Canal. Motility, edited by C. F. Code. Washington, D.C.: Am. Physiol. Soc., 1968, sect. 6, vol. IV, chapt. 92, p. 1861–1902.
 73. Doty, R. W., and J. F. Bosma. An electromyographic analysis of reflex deglutition. J. Neurophysiol. 19: 44–60, 1956.
 74. Doty, R. W., W. H. Richmond, and A. T. Storey. Effect of medullary lesions on coordination of deglutition. Exp. Neurol. 17: 91–106, 1967.
 75. Douglas, W. W. Histamines and antihistamines: 5‐hydroxytryptamine and antagonists. In: The Pharmacological Basis of Therapeutics (5th ed.), edited by L. S. Goodman and A. Gilman. New York: Macmillan, 1975, p. 590–629.
 76. Dubner, R., B. J. Sessle, and A. T. Storey. The Neural Basis of Oral and Facial Function. New York: Plenum, 1978, p. 483.
 77. Dubois, A., J. P. Jacobus, M. P. Grissom, R. R. Eng, and J. J. Conklin. Altered gastric emptying and prevention of radiation‐induced vomiting in dogs. Gastroenterology 86: 444–448, 1984.
 78. Eccles, J. C., F. Magni, and W. D. Willis. Depolarization of central terminals of group I afferent fibres from muscle. J. Physiol. Lond. 160: 62–93, 1962.
 79. Edwinson, L., J. Cervós‐Navaro, L.‐I. Larsson, C. Owman, and A.‐L. Rönnberg. Regional distribution of mast cells containing histamine, dopamine or 5‐hydroxytryptamine in the mammalian brain. Neurology 27: 878–883, 1977.
 80. Eiler, H., and R. Paddleford. Initiation of intestinal evacuation or vomiting (or both) in the dog by prostaglandin F2α injection: clinical potential. Am. J. Vet. Res. 40: 1731–1733, 1979.
 81. Ekberg, O. Closure of the laryngeal vestibule during deglutition. Acta Oto‐Laryngol. Stockh. 93: 123–129, 1982.
 82. Ekberg, O., and S. V. Sigurjónsson. Movement of the epiglottis during deglutition. Gastrointest. Radiol. 7: 101–107, 1982.
 83. Enjalbert, A., M. Hamon, S. Bergoin, and J. Boekaert. Postsynaptic serotonin‐sensitive adenylate cyclase in the central nervous system. II. Comparison with dopamine‐ and isoproterenol‐sensitive adenylate cyclase in rat brain. Mol. Pharmacol. 14: 11–23, 1978.
 84. Euler, C. von. On the central pattern generator for the basic rhythmicity. J. Appl. Physiol. 55: 1647–1659, 1983.
 85. Farley, I. J., and O. Hornykiewicz. Noradrenaline distribution in subcortical areas of the human brain. Brain Res. 126: 53–62, 1977.
 86. Fisher, M. A., T. R. Hendrix, J. M. Hunt, and A. J. Mirrells. Relationship between volume swallowed and velocity of the bolus ejected from the pharynx into the esophagus. Gastroenterology 74: 1238–1240, 1978.
 87. Frytak, S., and C. G. Moertel. Management of nausea and vomiting in the cancer patient. J. Am. Med. Assoc. 245: 393–396, 1981.
 88. Fuxe, K., and C. Owman. Cellular localization of monoamines in the area postrema of certain mammals. J. Comp. Neurol. 125: 337–354, 1956.
 89. Gaitonde, B. B., L. E. McCarthy, and H. L. Borison. Central emetic action and toxic effects of digitalis in cats. J. Pharmacol. Exp. Ther. 117: 409–415, 1964.
 90. Gerstener, H. B. Reaction to short‐term radiation in man. Ann. Rev. Med. 11: 289–302, 1960.
 91. Getting, P. A., P. R. Lennard, and R. I. Hume. Central pattern generator mediated swimming in Tritonia. I. Identification and synaptic interactions. J. Neurophysiol. 44: 151–14, 1980.
 92. Gidda, J. S., B. W. Cobb, and R. K. Goyal. Modulation of esophageal peristalsis by vagal efferent stimulation in opossum. J. Clin. Invest. 68: 1411–1419, 1981.
 93. Gidda, J. S., and R. K. Goyal. Influence of successive vagal stimulation on contractions in esophageal smooth muscle of opossum. J. Clin. Invest. 71: 1095–1103, 1983.
 94. Gidda, J. S., and R. K. Goyal. Swallow‐evoked action potentials in vagal preganglionic efferents. J. Neurophysiol. 52: 1169–1180, 1984.
 95. Gonella, J., J. P. Niel, and C. Roman. Vagal control of lower oesophageal sphincter motility in the cat. J. Physiol. Lond. 273: 647–664, 1977.
 96. Gralla, E. J., J. P. Sabo, D. W. Hayden, M. G. Yochmowitz, and J. L. Mattsson. The effect of selected drugs in first‐stage radioemesis in beagle dogs. Radiat. Res. 78: 286–295, 1979.
 97. Grillner, S., and P. Wallen. Central pattern generators for locomotion, with special reference to vertebrates. Ann. Rev. Neurosci. 8: 233–261, 1985.
 98. Gwyn, D. G., R. A. Leslie, and D. A. Hopkins. Gastric afferents to the nucleus of the solitary tract in the cat. Neurosci. Lett. 14: 13–17, 1979.
 99. Gylys, J. A., K. M. Doran, and J. P. Buyniski. Antagonism of cisplatin induced emesis in the dog. Res. Commun. Chem. Pathol. Pharmacol. 23: 61–68, 1979.
 100. Harding, R. K., Hugenholtz, H., M. Keaney, and J. Kucharizyk. Discrete lesions of the area postrema abolish radiation‐induced emesis in the dog. Neurosci. Lett. 53: 95–100, 1985.
 101. Hartline, D. K., and D. V. Gossie, Jr. Pattern generation in the lobster (Panulirus) stomotogastric ganglion. I. Pyloric neuron kinetics and synaptic interactions. Biol. Cybern. 33: 209–222, 1979.
 102. Hashimoto, I., S. Nemoto, and K. Sano. Hyperexcitable state of the brainstem in children with post‐traumatic vomiting as evidenced by brainstem auditory‐evoked potentials. Neurol. Res. 6: 81–84, 1984.
 103. Hatcher, R. A., and S. Weiss. Studies on vomiting. J. Pharmacol. 22: 139–193, 1923.
 104. Haywood, J. R., G. D. Fink, J. Buggy, M. I. Phillips, and M. J. Brody. The area postrema plays no role in the pressure action of angiotensin in the rat. Am. J. Physiol. 239 (Heart Circ. Physiol. 8): H108–H113, 1980.
 105. Hedges, R. B., C. D. McLean, and F. A. Thompson. A cinefluorographic study of tongue patterns in function. Angle Orthod. 35: 253–268, 1965.
 106. Hinrichsen, C. F. L., and C. D. Watson. Brainstem projections to the facial nucleus of the rat. Brain Behav. Evol. 22: 153–163, 1983.
 107. Hockman, C. H., D. Bieger, and A. Weerasuriya. Supranuclear pathways of swallowing. Prog. Neurobiol. 12: 15–32, 1979.
 108. Holstege, G., G. Graveland, C. Bijker‐Biemond, and I. Schuddenboom. Location of motoneurons innervating soft palate, pharynx and upper esophagus. Anatomical evidence for a possible swallowing center in the pontine reticular formation. Brain Behav. Evol. 23: 47–62, 1983.
 109. Holstege, G., H. G. J. M. Kuypers, and J. J. Dekker. The organization of the bulbar fibre connections to the trigeminal, facial and hypoglossal motor nuclei. Brain 10: 265–286, 1977.
 110. Hosoya, Y., and M. Matsushita. A direct projection from the hypothalamus to the area postrema in the rat, as demonstrated by the HRP and autoradiographic methods. Brain Res. 214: 144–149, 1981.
 111. Hrychyshyn, A. W., and J. V. Basonajian. Electromyography of the oral stage of swallowing in man. Am. J. Anat. 133: 333–340, 1972.
 112. Hulse, E. V., and G. Patrick. A model for treating postirradiation nausea and vomiting in man: the action of insulin in abolishing radiation‐induced delay in gastric emptying in the rat. Br. J. Radiol. 50: 645–651, 1977.
 113. Ikeda, M., S. Kubo, and Y. Iwase. The response of medullary reticular neurones to electrical stimulation of the chemoreceptor trigger zone in area postrema of the dog. J. Physiol. Soc. Jpn. 32: 600–605, 1970.
 114. Innes, I. R., and M. Nickerson. Norepinephrine, epinephrine and the sympathomimetic amines. In: The Pharmacological Basis of Therapeutics (5th ed.), edited by L. S. Goodman and A. Gilman. New York: Macmillan, 1975, p. 477–513.
 115. Iwase, Y., M. Ikeda, and H. Yoshikawa. Induction of emesis by electrical stimulation of the surface of the medulla oblongata. J. Physiol. Soc. Jpn. 28: 712–713, 1967.
 116. Jean, A. Effet de lésions localisées du bulbe rachidien sur le stade oesophagien de la déglutition. J. Physiol. Paris 64: 507–516, 1972.
 117. Jean, A. Localisation et activité des motoneurones oesophagiens chez le mouton. J. Physiol. Paris 74: 737–742, 1978.
 118. Jean, A., M. Amri, and A. Calas. Connections between the ventral medullary swallowing area and the trigeminal motor nucleus of sheep studied by tracing techniques. J. Auton. Nerv. Syst. 7: 87–96, 1983.
 119. Jean, A., and A. Car. Inputs to the swallowing medullary neurons from the peripheral afferent fibers and the swallowing cortical area. Brain Res. 178: 567–572, 1979.
 120. Jean, A., A. Car, and C. Roman. Comparison of activity in pontine versus medullary neurones during swallowing. Exp. Brain Res. 22: 211–220, 1975.
 121. Jenkins, L. C., and D. Lahay. Central mechanisms of vomiting related to catecholamine response: anesthetic implications. Can. Anaesth. Soc. J. 18: 434–441, 1971.
 122. Joy, M. D. The intramedullary connections of the area postrema involved in the central cardiovascular response to angiotensin II. Clin. Sci. 41: 89–100, 1971.
 123. Joy, M. D., and R. D. Lowe. Evidence that the area postrema mediates the central cardiovascular response to angiotensin. Nature Lond. 228: 1303–1304, 1970.
 124. Kalia, M., and M. M. Mesulum. Brain stem projections of sensory and motor components of the vagus complex in the cat. I. The cervical vagus and nodose ganglion. J. Comp. Neurol. 193: 435–465, 1980.
 125. Kalia, M., and R. V. Welles. Brain stem projections of the aortic nerve in the cat: a study using tetramethyl benzidine as the substrate for horseradish peroxidase. Brain Res. 188: 23–32, 1980.
 126. Kenrich, M. M., R. C. Bredfeldt, C. D. Sheridan, and A. D. Monroe. Bilateral injury to the hypoglossal nerve. Arch. Phys. Med. Rehabil. 58: 578–582, 1977.
 127. Kessler, J. P., and A. Jean. Identification of the medullary swallowing regions in the rat. Exp. Brain Res. 57: 256–266, 1985.
 128. Kessler, J. P., and A. Jean. Inhibition of the swallowing reflex by local application of serotoninergic agents into the nucleus of the solitary tract. Eur. J. Pharmacol. 118: 77–85, 1985.
 129. Klara, P. M., and K. R. Brizzee. Ultrastructural aspects of ependymal cells covering the feline area postrema. In: Proc. 34th Annu. Meeting Electron Microsc. Soc. America, edited by G. W. Bailey. Baton Rouge, LA: Claitor's, 1976, p. 120–121.
 130. Klara, P. M., and K. R. Brizzee. Ultrastructure of the feline area postrema. J. Comp. Neurol. 171: 409–431, 1977.
 131. Kuru, M., and S. Sugihara. Contributions to the knowledge of bulbar autonomic centres. II. Relationship of the vagal nuclei to the gastro‐jejunal motility. Jpn. J. Physiol. 5: 21–36, 1955.
 132. Laduron, P. M., and J. E. Leysen. Domperidone, a specific in vitro dopamine antagonist, devoid of in vivo central dopaminergic activity. Biochem. Pharmacol. 28: 2161–2165, 1979.
 133. Lanca, A. J., and D. van der Kooy. A serotonin‐containing pathway from the area postrema to the parabrachial nucleus in the rat. Neuroscience 14: 1117–1126, 1985.
 134. Laszlo, J. Treatment of nausea and vomiting caused by cancer chemotherapy. Cancer Treat. Rev. 9, Suppl. B: 3–9, 1982.
 135. Laszlo, J., and V. S. Lucas. Emesis as a critical problem in chemotherapy. N. Engl. J. Med. 305: 948–949, 1981.
 136. Lawn, A. M. The localization, in the nucleus ambiguus of the rabbit, of the cells of origin of motor nerve fibers in the glossopharyngeal nerve and various branches of the vagus nerve by means of retrograde degeneration. J. Comp. Neurol. 127: 293–306, 1966.
 137. Leslie, R. A. Neuroactive substances in the dorsal vagal complex of the medulla oblongata: nucleus of the tractus solitarius, area postrema, and dorsal motor nucleus of the vagus. Neurochem. Int. 7: 191–211. 1985.
 138. Leslie, R. A., D. G. Gwyn, and D. A. Hopkins. The ultrastructure of the subnucleus gelatinosus of the nucleus of the tractus solitarius in the cat. J. Comp. Neurol. 206: 109–118, 1982.
 139. Leslie, R. A., and N. N. Osborne. Amines and other transmitter‐like compounds in the bovine area postrema. Brain Res. Bull. 13: 357–362, 1984.
 140. Levey, S., J. E. Harroun, and C. J. Smyth. Serum glutamic acid levels and the occurrence of nausea and vomiting after the intravenous administration of amino acid mixtures. J. Lab. Clin. Med. 34: 1238–1248, 1949.
 141. Lindstrom, P. A., and K. R. Brizzee. Relief of intractable vomiting from surgical lesions in the area postrema. J. Neurosurg. 19: 228–236, 1962.
 142. Loewy, A. D., and H. Burton. Nuclei of the solitary tract: efferent projections to the lower brain stem and spinal cord of the cat. J. Comp. Neurol. 181: 421–450, 1978.
 143. Lowe, A. A. The neural regulation of tongue movements. Prog. Neurobiol. 15: 295–344, 1981.
 144. Lowe, A. A., S. Gurza, and B. J. Sessle. Regulation of genioglossus and masseter muscle activity in man. Arch. Oral Biol. 22: 579–584, 1977.
 145. Lumsden, K., and W. S. Holden. The act of vomiting in man. Gut 10: 173–179, 1969.
 146. Lushbaugh, C. C., F. Comas, and R. Hofstra. Clinical studies of radiation effects in man: a preliminary report of a retrospective search for dose‐relationships in the prodromal syndrome. Radiat. Res. 7: 398–412, 1967.
 147. Magendie, F. Précis Elémentaire de Physiologie. Paris: Meguignon‐Marvis, 1817, vol. 2.
 148. Magoun, H. W., S. W. Ranson, and C. Fisher. Corticofugal pathways for mastication, lapping and other motor functions in the cat. Arch. Neurol. Psychiatry 30: 212–308, 1933.
 149. Malagelada, J., and M. Camilleri. Unexplained vomiting: a diagnostic challenge. Ann. Intern. Med. 101: 211–218, 1984.
 150. Manchanda, S. K., and I. S. Aneja. Afferent projections of superior laryngeal nerve in the medulla oblongata‐localization of the swallowing centre. Indian J. Physiol. Pharmacol. 16: 67–73, 1972.
 151. Manni, E., M. Lucchi, G. Filippi, and R. Bortolami. Area postrema and the mesencephalic trigeminal nucleus. Exp. Neurol. 77: 39–55, 1982.
 152. Mánsson, I., and N. Sandberg. Effects of surface anesthesia on deglutition in man. Laryngoscope 84: 427–437, 1974.
 153. Marckwald, M. Über die Ausbreitung der Erregung und Hemmung vom Schluckcentrum auf das Atemcentrum. Z. Biol. 25: 1–54, 1889.
 154. Marks, J. H. Use of chlorpromazine in radiation sickness and nausea from other causes. N. Engl. J. Med. 250: 999–1001, 1954.
 155. Matsnev, E. I., J. Y. Yakovleva, I. K. Tarasov, V. N. Alekseeven, C. N. Kornilova, A. D. Matetv, and G. I. Gorgiladze. Space motion sickness: phenomenology, countermeasures, and mechanisms. Aviat. Space Environ. Med. 54: 312–317, 1983.
 156. Mattsson, J. L., and M. G. Yochmowitz. Radiation‐induced emesis in monkeys. Radiat. Res. 82: 191–199, 1980.
 157. McCarthy, L. E., and H. L. Borison. Cisplatin‐induced vomiting eliminated by ablation of the area postrema in cats. Cancer Treat. Rev. 68: 401–404, 1984.
 158. Meadows, J. C. Dysphagia in unilateral cerebral lesions. J. Neurol. Neurosurg. Psychiatry 36: 853–860, 1973.
 159. Mehler, W. R. Observations on the connectivity of the parvicellular reticular formation with respect to a vomiting center. Brain Behav. Evol. 23: 63–80, 1983.
 160. Miller, A. D., and V. J. Wilson. “Vomiting center” reanalyzed: an electrical stimulation study. Brain Res. 270: 154–158, 1983.
 161. Miller, A. D., and V. J. Wilson. Vestibular‐induced vomiting after vestibulocerebellar lesions. Brain Behav. Evol. 23: 26–31, 1983.
 162. Miller, A. J. Significance of sensory inflow to the swallowing reflex. Brain Res. 43: 147–159, 1972.
 163. Miller, A. J. Characteristics of the swallowing induced by peripheral nerve and brain stem stimulation. Exp. Neurol. 34: 210–222, 1972.
 164. Miller, A. J. Deglutition. Physiol. Rev. 62: 129–184, 1982.
 165. Miller, A. J., and J. P. Bowman. Divergent synaptic influences affecting discharge patterning of genioglossus motor units. Brain Res. 78: 179–191, 1974.
 166. Miller, A. J., and R. F. Loizzi. Anatomical and functional differentiation of superior laryngeal nerve fibers affecting swallowing and respiration. Exp. Neurol. 42: 369–387, 1974.
 167. Miller, F. R. The cortical paths for mastication and deglutition. J. Physiol. Lond. 53: 473–478, 1920.
 168. Miller, F. R., and C. S. Sherrington. Some observations on the buccopharyngeal stage of reflex deglutition in the cat. Q. J. Exp. Physiol. 9: 147–186, 1916.
 169. Mitchell, W. G., R. S. Greenwood, and J. A. Messenheimer. Abdominal epilepsy: cyclic vomiting as the major symptom of simple partial seizures. Arch. Neurol. 40: 251–252, 1983.
 170. Miyazaki, T., Y. Yoshida, M. Hirano, T. Shin, and T. Kanaseki. Central location of the motoneurons supplying the thyrohyoid and the geniohyoid muscles as demonstrated by horseradish peroxidase method. Brain Res. 219: 423–427, 1981.
 171. Moher, D., A. Z. Arthur, and J. L. Pater. Anticipatory nausea and/or vomiting. Cancer Treat. Rev. 11: 257–264, 1984.
 172. Money, K. E. Motion sickness. Physiol. Rev. 50: 1–39, 1970.
 173. Money, K. E. Biological effects of space travel. Can. Aeronaut. Space J. 27: 195–201, 1981.
 174. Money, K. E., and J. Friedberg. The role of the semicircular canals in causation of motion sickness and nystagmus in the dog. Can. J. Physiol. Pharmacol. 42: 793–801, 1964.
 175. Morest, D. K. A study of the structure of the area postrema with Golgi methods. Am. J. Anat. 107: 291–303, 1960.
 176. Morest, D. K. Ascending pathways from an osmotically sensitive region of the medulla oblongata. Exp. Neurol. 4: 413–423, 1961.
 177. Morest, D. K. Experimental study of the projections of the nucleus tractus solitarius and the area postrema in the cat. J. Comp. Neurol. 130: 277–299, 1967.
 178. Newton, B. W., B. Maley, C. Sasek, and H. Traurig. Distribution of FMRF‐NH2‐like immunoreactivity in rat and cat area postrema. Brain Res. Bull. 13: 391–399, 1984.
 179. Newton, B. W., B. Maley, and H. Traurig. The distribution of substance P, enkephalin, and serotonin immunoreactivities in the area postrema of the rat and cat. J. Comp. Neurol. 234: 87–104, 1985.
 180. Ogura, J. N., M. Kawasaki, and S. Takenouchi. Neurophysiologic observations on the adaptive mechanism of deglutition. Ann. Otol. Rhinol. Laryngol. 73: 1062–1082, 1964.
 181. Olney, J. W., V. Rhee, and T. De Gubareff. Neurotoxic effects of glutamate on mouse area postrema. Brain Res. 120: 151–157, 1977.
 182. Ossenkopp, K.‐P. Taste aversions conditioned with gamma radiation: attenuation by area postrema lesions in rats. Behav. Brain Res. 7: 297–305, 1983.
 183. Palazzo, M. G. A., and L. Strunin. Anesthesia and emesis. I. etiology. Can. Anaesth. Soc. J. 31: 178–187, 1984.
 184. Pedigo, N. W., Jr., and K. R. Brizzee. Muscarinic cholinergic receptors in area postrema and brainstem areas regulating emesis. Brain Res. Bull. 14: 169–177, 1985.
 185. Pellegrino, L. I., A. S. Pellegrino, and A. J. Cushman (editors). A Stereotaxic Atlas of the Rat Brain (2nd ed.). New York: Plenum, 1979.
 186. Peng, M. T. Locus of emetic action of epinephrine and dopa in dogs. J. Pharmacol. Exp. Ther. 139: 345–349, 1963.
 187. Pinsker, H. M. Integration of reflex activity and central pattern generation in intact Aplysia. J. Physiol. Paris 78: 775–785, 1982–83.
 188. Pommerenke, W. T. A study of the sensory areas eliciting the swallowing reflex. Am. J. Physiol. 84: 36–41, 1928.
 189. Pratt, A., R. M. Lazar, D. Penman, and J. C. Holland. Psychological parameters of chemotherapy‐induced conditioned nausea and vomiting: a review. Cancer Nurs. 7: 483–490, 1984.
 190. Price, M. T., M. E. Pusateri, S. E. Crow, S. Buchsbaum, J. W. Olney, and O. H. Lowry. Uptake of exogenous aspartate into circumventricular organs but not other regions of adult mouse brain. J. Neurochem. 42: 740–744, 1984.
 191. Priima, G. Y. Role of the superior laryngeal nerve in swallowing. Fiziol. Zh. SSSR IM I M Sechenova 44: 141–147, 1958.
 192. Rabin, B. M., W. A. Hunt, and J. Lee. Attenuation of radiation‐ and drug‐induced conditioned taste aversion following area postrema lesions in the rat. Radiat. Res. 93: 388–394, 1983.
 193. Rabin, B. M., W. A. Hunt, and J. Lee. Recall of a previously acquired conditioned taste aversion in rats following lesions of the area postrema. Physiol. Behav. 32: 503–506, 1984.
 194. Rattan, S., J. S. Gidda, and R. K. Goyal. Membrane potential and mechanical responses of the opossum esophagus to vagal stimulation and swallowing. Gastroenterology 85: 922–928, 1983.
 195. Reyntjens, A. Domperidone as an anti‐emetic: summary of research reports. Postgrad. Med. J. Suppl. 55: 50–54, 1979.
 196. Roberts, R. K. A cineradiographic investigation of pharyngeal deglutition. Br. J. Radiol. 30: 449–460, 1957.
 197. Robertson, R. M., and M. Moulius. Control of rhythmic behavior by a hierarchy of linked oscillators in crustacea. Neurosci. Lett. 21: 111–116, 1981.
 198. Roman, C., and A. Car. Contractions oesophagiennes produites par la stimulation de vague ou du bulbe rachidien. J. Physiol. Paris 59: 377–398, 1967.
 199. Roth, G. I., and W. S. Yamamoto. The microcirculation of the area postrema in the rat. J. Comp. Neurol. 133: 329–340, 1968.
 200. Rudomin, P. Presynaptic inhibition induced by vagal afferent volleys. J. Neurophysiol. 30: 964–981, 1967.
 201. Rudomin, P. Excitability changes of superior laryngeal, vagal and depressor afferent terminals produced by stimulation of the solitary tract nucleus. Exp. Brain Res. 6: 156–170, 1968.
 202. Sampson, S., and C. Eyzaguirre. Some functional characteristics of mechanoreceptors in the larynx of the cat. J. Neurophysiol. 27: 464–480, 1964.
 203. Schmitt, A., K. J. Yu, and B. J. Sessle. Excitatory and inhibitory influences from laryngeal and orofacial areas on tongue position in cat. Arch. Oral Biol. 18: 1121–1130, 1973.
 204. Selverston, A. I., and M. Moulins. Oscillatory neural networks. Annu. Rev. Physiol. 47: 29–48, 1985.
 205. Sessle, B. J. Excitatory and inhibitory inputs to single neurons in the solitary tract nucleus and adjacent reticular formation. Brain Res. 53: 319–331, 1973.
 206. Sessle, B. J. Presynaptic excitability changes induced in single laryngeal primary afferent fibres. Brain Res. 53: 333–342, 1973.
 207. Sessle, B. J. Chairman's Introduction. In: Mastication and Swallowing: Biological and Clinical Correlates, edited by B. J. Sessle and A. G. Hannon. Toronto: Univ. of Toronto Press, 1975, p. 44.
 208. Sessle, B. J., G. J. Ball, and G. E. Lucier. Suppressive influences from periaqueductal gray and nucleus raphe magnus on respiration and related reflex activities and on solitary tract neurons and effect of naloxone. Brain Res. 216: 145–161, 1981.
 209. Sessle, B. J., and A. G. Hannan. Mastication and Swallowing: Biological and Clinical Correlates, edited by B. J. Sessle and A. G. Hannon. Toronto: Univ. of Toronto Press, 1976.
 210. Sessle, B. J., and A. T. Storey. Peridontal and facial influences on the laryngeal input to the brain stem of the cat. Arch. Oral Biol. 17: 1583–1595, 1972.
 211. Sinclair, W. J. Role of the pharyngeal plexus in initiation of swallowing. Am. J. Physiol. 221: 1260–1263, 1971.
 212. SpaČek, J., and J. PaŘizek. The fine structure of the area postrema of the rat. Acta Morph. Acad. Sci. Hung. 17: 17–34, 1969.
 213. Speth, R. C., J. K. Wamsley, D. R. Gehlert, C. L. Chernicky, K. L. Barnes, and C. M. Ferrario. Angiotensin II receptor localization in the canine CNS. Brain Res. 326: 137–143, 1985.
 214. Stefanini, E., and Y. Clement‐Cormier. Detection of dopamine receptors in the area postrema. Eur. J. Pharmacol. 74: 257–260, 1981.
 215. Storey, A. T. Laryngeal initiation of swallowing. Exp. Neurol. 20: 359–365, 1968.
 216. Storey, A. T. A functional analysis of sensory units innervating epiglottis and larynx. Exp. Neurol. 20: 366–383, 1968.
 217. Stoudemire, A., P. Cotanch, and J. Laszlo. Recent advances in the pharmacologic and behavioral management of chemotherapy‐induced emesis. Arch. Intern. Med. 144: 1029–1033, 1984.
 218. Sumi, T. The activity of brain‐stem respiratory neurons and spinal respiratory motoneurons during swallowing. J. Neurophysiol. 26: 466–477, 1963.
 219. Sumi, T. Neuronal mechanisms in swallowing. Pfluegers Arch. 278: 467–477, 1964.
 220. Sumi, T. Some properties of cortically evoked swallowing and chewing in rabbits. Brain Res. 15: 107–120, 1969.
 221. Sumi, T. Synaptic potentials of hypoglossal motoneurons and their relation to reflex deglutition. Jpn. J. Physiol. 19: 68–79, 1969.
 222. Sumi, T. Role of the pontine reticular formation in the neural organization of deglutition. Jpn. J. Physiol. 22: 295–314, 1972.
 223. Thompson, D. G., and J. R. Malagelada. Vomiting and the small intestine. Dig. Dis. Sci. 27: 1121–1125, 1982.
 224. Thoron, C. D., J. A. Riancho, and H. L. Borison. Lack of protection against ouabain cardiotoxicity after chronic ablation of the area postrema in cat. Exp. Neurol. 85: 574–583, 1984.
 225. Trounce, J. R. Antiemetics and cytotoxic drugs. Br. Med. J. 286: 327–329, 1983.
 226. Tyler, D. B., and P. Bard. Motion sickness. Physiol. Rev. 29: 311–369, 1949.
 227. Van der Kooy, D. Area postrema: site where cholecystokinin acts to decrease food intake. Brain Res. 295: 345–347, 1984.
 228. Van der Kooy, D., and L. Koda. Organization of the projection of the circumventricular AP organ: the area postrema in the rat. J. Comp. Neurol. 219: 328–338, 1983.
 229. Van Houten, M., M. L. Mangiapane, I. A. Reid, and W. F. Ganong. [SAR1, ALA8] Angiotensin II in cerebrospinal fluid blocks the binding of blood‐borne [125I] angiotensin II to the circumventricular organs. Neuroscience 10: 1421–1426, 1983.
 230. Vigier, D., and P. Portalier. Efferent projections of the area postrema demonstrated by autoradiography. Arch. Ital. Biol. 117: 308–324, 1979.
 231. Vigier, D., and A. Rouviere. Afferent and efferent connections of the area postrema demonstrated by the horseradish peroxidase method. Arch. Ital. Biol. 117: 325–339, 1979.
 232. Vitti, M., J. V. Basmajian, P. L. Ouellette, D. L. Mitchell, W. P. Eastman, and R. D. Seaborn. Electromyographic investigations of the tongue and circumoral muscular sling with fine wire electrodes. J. Dent. Res. 54: 844–849, 1975.
 233. Waldrop, M. M. Astronauts can't stomach zero gravity. Science Wash. DC 218: 1106, 1982.
 234. Wang, S. C. Physiology and Pharmacology of the Brain Stem. Mount Kisco, NY: Futura, 1980.
 235. Wang, S. C., and H. L. Borison. Copper sulfate emesis: a study of afferent pathways from the gastrointestinal tract. Am. J. Physiol. 164: 520–526, 1951.
 236. Wang, S. C., and H. L. Borison. A new concept of organization of the central emetic mechanism: recent studies on the sites of action of apomorphine, copper sulfate and cardiac glycosides. Gastroenterology 22: 1–12, 1952.
 237. Wang, S. C., and H. I. Chinn. Experimental motion sickness in dogs. Functional importance of chemoreceptive emetic trigger zone. Am. J. Physiol. 178: 111–116, 1954.
 238. Wang, S. C., and H. I. Chinn. Experimental motion sickness in dogs. Importance of labyrinth and vestibular cerebellum. Am. J. Physiol. 185: 617–623, 1956.
 239. Wang, S. C., and V. V. Glaviano. Locus of emetic action of morphine and hydergine in dogs. J. Pharmacol. Exp. Ther. 3: 329–334, 1954.
 240. Wang, S. C., A. A. Renzi, and H. I. Chinn. Mechanism of emesis following x‐irradiation. Am. J. Physiol. 193: 335–339, 1958.
 241. Wang, S. C., and R. L. Tyson. Central nervous pathways of experimental motion sickness. Int. Rec. Med. 167: 641–650, 1954.
 242. Weeks, J. C. Neuronal basis of leech swimming: separation of swim initiation pattern generation, and intersegmental coordination by selective lesions. J. Neurophysiol. 45: 698–723, 1981.
 243. Weerasuriya, A., D. Bieger, and C. H. Hockman. Basal forebrain facilitation of reflex swallowing in the cat. Brain Res. 174: 119–133, 1979.
 244. Weerasuriya, A., D. Bieger, and C. H. Hockman. Interaction between primary afferent nerves in the elicitation of reflex swallowing. Am. J. Physiol. 239 (Regulatory Integrative Comp. Physiol. 8): 407–414, 1980.
 245. Willis, G. L., J. Hansky, and G. C. Smith. Ventricular, paraventricular and circumventricular structures involved in peptide‐induced satiety. Regul. Pept. 9: 87–99, 1984.
 246. Wislocki, G. B., and T. J. Putnam. Note on the anatomy of the areae postremae. Anat. Rec. 19: 281–287, 1920.
 247. Wruble, L. D., R. H. Rosenthal, and W. L. Webb. Psychogenic vomiting: a review. Am. J. Gastroenterol. 77: 318–321, 1982.
 248. Wyman, R. J. Neurophysiology of the motor output pattern generator for breathing. Federation Proc. 35: 2013–2023, 1976.
 249. Yasko, J. M. Holistic management of nausea and vomiting caused by chemotherapy. Top. Clin. Nurs. 7: 26–38, 1985.
 250. Ylitalo, P., H. Karppanen, and M. Paasonen. Is the area postrema a control centre of blood pressure? Nature Lond. 274: 58–59, 1974.
 251. Zandberg, P., M. Palkovits, and W. De Jong. The area postrema and control of arterial blood pressure; absence of hypertension after excision of the area postrema in rats. Pfluegers Arch. 372: 169–173, 1977.
 252. Zarbin, K. A., R. B. Innis, J. K. Wansley, S. H. Snyder, and M. H. Kuhar. Autoradiographic localization of cholecystokinin receptors in rodent brain. J. Neuroscience 3: 877–906, 1983.

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David O. Carpenter. Central nervous system mechanisms in deglutition and emesis. Compr Physiol 2011, Supplement 16: Handbook of Physiology, The Gastrointestinal System, Motility and Circulation: 685-714. First published in print 1989. doi: 10.1002/cphy.cp060118