Botzinger complex explained

In mammals, the Bötzinger complex (BötC) is a group of neurons located in the rostral ventrolateral medulla, and ventral respiratory column. In the medulla, this group is located caudally to the facial nucleus and ventral to nucleus ambiguus.^{[1] [2]}

Function

The Bötzinger complex plays an important role in controlling breathing^{[3] [4]} and responding to hypoxia.^{[5] [6]} The Bötzinger complex consists primarily of glycinergic neurons^[7] which inhibit respiratory activity. Of the respiratory cycle phases BötC generates post-inspiratory (Post-I) activity and augmenting expiratory (aug-e) activity.^{[8] [9] [10]}

Name

The Bötzinger complex was named by UCLA Professor Jack Feldman in 1978, after a bottle of white wine named Botzinger present at his table during a scientific meeting in Hirschhorn, Germany, that year.^[11]

Connections

The Bötzinger Complex has projections to

• Phrenic pre-motor neurons in the medulla^[12]
• Phrenic motor neurons in the cervical spinal cord^{[13] [14]}
• The dorsal respiratory group (DRG) ^{[13] [15]}
• Ventral respiratory group (VRG)^{[12] [13] [16]}
• Pre-Bötzinger complex^[17]
• Bötzinger complex ^{[2] [13] [18] [19]}
• Parabrachial Kolliker-Fuse nucleus^[20]

Only augmenting expiratory neurons of BötC, which are exclusively glycinergic, project to the phrenic nucleus.^{[21] [14]}

Projections to the Bötzinger complex include the nucleus tractus solitarii (NTS)^{[22] [23]} the DRG and the VRG.^[24]

Physiology

These neurons are intrinsic pacemakers.^[25] Post-I neurons display an initial burst of activity followed by decrease in activity at the end of inspiration. Aug-E neurons begin firing during the E2 phase and end before the phrenic nerve burst.^{[19] [26]}

Notes and References

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2. Otake K, Sasaki H, Mannen H, Ezure K. Morphology of expiratory neurons of the Bötzinger complex: an HRP study in the cat. . J Comp Neurol . 1987 . 258 . 4 . 565–79 . 10.1002/cne.902580407 . 3034989 .
3. Bongianni F, Corda M, Fontana GA, Pantaleo T. Reciprocal connections between rostral ventrolateral medulla and inspiration-related medullary areas in the cat. . Brain Res . 1991 . 565 . 1 . 171–4 . 10.1016/0006-8993(91)91751-l. 1773353 .
4. Guyenet PG. Neural structures that mediate sympathoexcitation during hypoxia. . Respir Physiol . 2000 . 121 . 2–3 . 147–62 . 10.1016/s0034-5687(00)00125-0. 10963771 .
5. Hirooka Y, Polson JW, Potts PD, Dampney RA. Hypoxia-induced Fos expression in neurons projecting to the pressor region in the rostral ventrolateral medulla. . Neuroscience . 1997 . 80 . 4 . 1209–24 . 10.1016/s0306-4522(97)00111-5. 9284071 .
6. Nitsos I, Walker DW. The distribution of FOS-immunoreactive neurons in the brainstem, midbrain and diencephalon of fetal sheep in response to acute hypoxia in mid and late gestation. . Brain Res Dev Brain Res . 1999 . 114 . 1 . 9–26 . 10.1016/s0165-3806(99)00010-3. 10209238 .
7. Winter SM, Fresemann J, Schnell C, Oku Y, Hirrlinger J, Hülsmann S. Glycinergic interneurons are functionally integrated into the inspiratory network of mouse medullary slices. . Pflügers Arch . 2009 . 458 . 3 . 459–69 . 19238427 . 10.1007/s00424-009-0647-1 . 2691554 .
8. Richter A, Heyne K, Sagebiel J, Weber M. [Respiratory emergency in the newborn infant: extreme laryngotracheo-esophageal cleft (esophagotrachea)]. . Monatsschr Kinderheilkd . 1986 . 134 . 12 . 874–7 . 3821744 .
9. Richter DW. Generation and maintenance of the respiratory rhythm. . J Exp Biol . 1982 . 100 . 93–107 . 6757372 .
10. Merrill EG. Where are the real respiratory neurons? . Fed Proc . 1981 . 40 . 9 . 2389–94 . 7250385 .
11. Web site: Hartman . Kristen . From the President: A Sigh is (Not) Just a Sigh . . . – Advanced Targeting Systems . Advanced Targeting Systems – Advanced Targeting Systems . 2016-04-02 . 2024-06-20.
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13. Otake K, Sasaki H, Ezure K, Manabe M. Axonal projections from Bötzinger expiratory neurons to contralateral ventral and dorsal respiratory groups in the cat. . Exp Brain Res . 1988 . 72 . 1 . 167–77 . 10.1007/bf00248512. 3169184 .
14. Tian GF, Peever JH, Duffin J. Bötzinger-complex expiratory neurons monosynaptically inhibit phrenic motoneurons in the decerebrate rat. . Exp Brain Res . 1998 . 122 . 2 . 149–56 . 10.1007/s002210050502. 9776513 .
15. Lipski J, Merrill EG. Electrophysiological demonstration of the projection from expiratory neurones in rostral medulla to contralateral dorsal respiratory group. . Brain Res . 1980 . 197 . 2 . 521–4 . 10.1016/0006-8993(80)91140-3. 7407571 .
16. Bryant TH, Yoshida S, de Castro D, Lipski J. Expiratory neurons of the Bötzinger Complex in the rat: a morphological study following intracellular labeling with biocytin. . J Comp Neurol . 1993 . 335 . 2 . 267–82 . 10.1002/cne.903350210 . 8227518 .
17. Richter DW, Smith JC. Respiratory rhythm generation in vivo. . Physiology . 2014 . 29 . 1 . 58–71 . 24382872 . 10.1152/physiol.00035.2013 . 3929116.
18. Shen L, Li YM, Duffin J. Inhibitory connections among rostral medullary expiratory neurones detected with cross-correlation in the decerebrate rat. . Pflügers Arch . 2003 . 446 . 3 . 365–72 . 10.1007/s00424-003-1024-0 . 12687375 .
19. Smith JC, Abdala AP, Koizumi H, Rybak IA, Paton JF. Spatial and functional architecture of the mammalian brain stem respiratory network: a hierarchy of three oscillatory mechanisms. . J Neurophysiol . 2007 . 98 . 6 . 3370–87 . 17913982 . 10.1152/jn.00985.2007 . 2225347 .
20. Ezure K, Tanaka I, Saito Y. Brainstem and spinal projections of augmenting expiratory neurons in the rat. . Neurosci Res . 2003 . 45 . 1 . 41–51 . 10.1016/s0168-0102(02)00197-9. 12507723 .
21. Schreihofer AM, Stornetta RL, Guyenet PG. Evidence for glycinergic respiratory neurons: Bötzinger neurons express mRNA for glycinergic transporter 2. . J Comp Neurol . 1999 . 407 . 4 . 583–97 . 10.1002/(sici)1096-9861(19990517)407:4<583::aid-cne8>3.0.co;2-e. 10235646 .
22. Accorsi-Mendonça D, Bonagamba LG, Leão RM, Machado BH. Are L-glutamate and ATP cotransmitters of the peripheral chemoreflex in the rat nucleus tractus solitarius? . Exp Physiol . 2009 . 94 . 1 . 38–45 . 10.1113/expphysiol.2008.043653 . 18931046 . free .
23. Ruff F, Caubarrere I, Salem A, Dubois F, Duroux P. [Regional distribution of pulmonary perfusion during fluid overload in man]. . Ann Anesthesiol Fr . 1975 . 16 Spec No 2-3 . 164–8 . 9861 .
24. Douse MA, Duffin J. Projections to Bötzinger expiratory neurons by dorsal and ventral respiratory group neurons. . NeuroReport . 1992 . 3 . 5 . 393–6 . 10.1097/00001756-199205000-00004. 1633274 .
25. Almado CE, Leão RM, Machado BH. Intrinsic properties of rostral ventrolateral medulla presympathetic and bulbospinal respiratory neurons of juvenile rats are not affected by chronic intermittent hypoxia. . Exp Physiol . 2014 . 99 . 7 . 937–50 . 10.1113/expphysiol.2013.077800 . 24728679 . free .
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