Journal of Neurophysiology, Vol 73, Issue 4 1452-1461, Copyright © 1995 by APS

ARTICLES

Pre-Botzinger complex in the cat

S. W. Schwarzacher, J. C. Smith and D. W. Richter
Department of Neurophysiology, University of Gottingen, Germany.

1. Patterns of respiratory neuronal activity were examined in pentobarbitone anesthetized adult cats in a circumscribed area of the ventrolateral medulla, which has previously been defined as the pre-Botzinger complex (pre-BOTC) from electrophysiological and morphological criteria in the brain stem-spinal cord preparation of the neonatal rat. The pre-BOTC has been proposed to play a critical role in respiratory rhythm generation in mammals, but electrophysiological properties of the region have not been thoroughly characterized in the adult brain stem in vivo. 2. From intra- and extracellular recordings, we verified the existence of a well-defined zone with a distinct profile of neuronal activity between the rostral Botzinger complex containing expiratory neurons and the more caudal medullary pool of inspiratory neurons of the ventral respiratory group (VRG) in the para-ambigual region. This zone corresponds to the pre-BOTC. It was characterized by a concentration of the various types of respiratory neurons, particularly those proposed to be involved in respiratory phase transitions, including neurons discharging immediately before the onset of inspiratory phase activity (pre-inspiratory neurons), early-inspiratory, and postinspiratory neurons. The majority of these neurons were presumed interneurons because they were not antidromically activated by spinal cord or cranial nerve stimulation. 3. The locus of the pre-BOTC corresponded histologically to the rostral part of the nucleus ambiguus and ventrolateral reticular formation. It was located caudal to the retrofacial nucleus and rostral to the lateral reticular nucleus, extending 3.0-3.5 mm rostral to the obex, and 3.2-4.0 mm lateral from the midline. This location was homologous to that established in the neonatal rat. 4. Pre-inspiratory neurons (pre-I neurons) were specifically found in the pre-BOTC. Intracellular recordings from these neurons revealed two types of activity patterns. Type 1 of pre-I neurons exhibited a steady membrane depolarization during expiration and a steep membrane depolarization with a high-frequency burst of action-potential discharge during the phase transition from expiration to inspiration. This was followed by a decline of depolarization and spike discharge during the remainder of the inspiratory phase. A second type of pre-I neurons exhibited a secondary graded membrane depolarization and burst discharge during the late-inspiratory period. 5. Synaptic events were examined in other respiratory neurons during the 40-160 ms preceding the onset of phrenic nerve activity when pre-I neurons exhibited peak spike discharge. Early-inspiratory, throughout-respiratory, and postinspiratory neurons were disinhibited during this period, whereas stage-2 expiratory neurons exhibited a decrease in spike activity and repolarization.(ABSTRACT TRUNCATED AT 400 WORDS)

This article has been cited by other articles:

				H. Koizumi, C. G. Wilson, S. Wong, T. Yamanishi, N. Koshiya, and J. C. Smith Functional Imaging, Spatial Reconstruction, and Biophysical Analysis of a Respiratory Motor Circuit Isolated In Vitro J. Neurosci., March 5, 2008; 28(10): 2353 - 2365. [Abstract] [Full Text] [PDF]

				A. Ruangkittisakul, L. Secchia, T. D. Bornes, D. M. Palathinkal, and K. Ballanyi Dependence on extracellular Ca2+/K+ antagonism of inspiratory centre rhythms in slices and en bloc preparations of newborn rat brainstem J. Physiol., October 15, 2007; 584(2): 489 - 508. [Abstract] [Full Text] [PDF]

				K. Shiba, K. Nakazawa, K. Ono, and T. Umezaki Multifunctional Laryngeal Premotor Neurons: Their Activities during Breathing, Coughing, Sneezing, and Swallowing J. Neurosci., May 9, 2007; 27(19): 5156 - 5162. [Abstract] [Full Text] [PDF]

				A. Ruangkittisakul, S. W. Schwarzacher, L. Secchia, B. Y. Poon, Y. Ma, G. D. Funk, and K. Ballanyi High Sensitivity to Neuromodulator-Activated Signaling Pathways at Physiological [K+] of Confocally Imaged Respiratory Center Neurons in On-Line-Calibrated Newborn Rat Brainstem Slices. J. Neurosci., November 15, 2006; 26(46): 11870 - 11880. [Abstract] [Full Text] [PDF]

				A. Y. Fong and J. T. Potts Neurokinin-1 receptor activation in Botzinger complex evokes bradypnoea J. Physiol., September 15, 2006; 575(3): 869 - 885. [Abstract] [Full Text] [PDF]

				P. M. Lalley Opiate slowing of feline respiratory rhythm and effects on putative medullary phase-regulating neurons Am J Physiol Regulatory Integrative Comp Physiol, May 1, 2006; 290(5): R1387 - R1396. [Abstract] [Full Text] [PDF]

				S. P. Lieske and J.-M. Ramirez Pattern-Specific Synaptic Mechanisms in a Multifunctional Network. I. Effects of Alterations in Synapse Strength J Neurophysiol, March 1, 2006; 95(3): 1323 - 1333. [Abstract] [Full Text] [PDF]

				J. A. N. Fisher, V. A. Marchenko, A. G. Yodh, and R. F. Rogers Spatiotemporal Activity Patterns During Respiratory Rhythmogenesis in the Rat Ventrolateral Medulla J Neurophysiol, March 1, 2006; 95(3): 1982 - 1991. [Abstract] [Full Text] [PDF]

				A. T. Lovering, J. J. Fraigne, W. L. Dunin-Barkowski, E. H. Vidruk, and J. M. Orem Medullary Respiratory Neural Activity During Hypoxia in NREM and REM Sleep in the Cat J Neurophysiol, February 1, 2006; 95(2): 803 - 810. [Abstract] [Full Text] [PDF]

				W. A. Janczewski and J. L. Feldman Distinct rhythm generators for inspiration and expiration in the juvenile rat J. Physiol., January 15, 2006; 570(2): 407 - 420. [Abstract] [Full Text] [PDF]

				F. P. Elsen and J.-M. Ramirez Postnatal Development Differentially Affects Voltage-Activated Calcium Currents in Respiratory Rhythmic Versus Nonrhythmic Neurons of the Pre-Botzinger Complex J Neurophysiol, August 1, 2005; 94(2): 1423 - 1431. [Abstract] [Full Text] [PDF]

				M. Krolo, V. Tonkovic-Capin, A. G. Stucke, E. A. Stuth, F. A. Hopp, C. Dean, and E. J. Zuperku Subtype Composition and Responses of Respiratory Neurons in the Pre-Botzinger Region to Pulmonary Afferent Inputs in Dogs J Neurophysiol, May 1, 2005; 93(5): 2674 - 2687. [Abstract] [Full Text] [PDF]

				I. C. Solomon Glutamate Neurotransmission Is Not Required for, But May Modulate, Hypoxic Sensitivity of Pre-Botzinger Complex In Vivo J Neurophysiol, March 1, 2005; 93(3): 1278 - 1284. [Abstract] [Full Text] [PDF]

				D. M. Baekey, K. F. Morris, S. C. Nuding, L. S. Segers, B. G. Lindsey, and R. Shannon Ventrolateral medullary respiratory network participation in the expiration reflex in the cat J Appl Physiol, June 1, 2004; 96(6): 2057 - 2072. [Abstract] [Full Text] [PDF]

				I. C. Solomon Ionotropic excitatory amino acid receptors in pre-Botzinger complex play a modulatory role in hypoxia-induced gasping in vivo J Appl Physiol, May 1, 2004; 96(5): 1643 - 1650. [Abstract] [Full Text] [PDF]

				N. M. Mellen, M. Roham, and J. L. Feldman Afferent modulation of neonatal rat respiratory rhythm in vitro: cellular and synaptic mechanisms J. Physiol., May 1, 2004; 556(3): 859 - 874. [Abstract] [Full Text] [PDF]

				J. A. Neubauer and J. Sunderram Oxygen-sensing neurons in the central nervous system J Appl Physiol, January 1, 2004; 96(1): 367 - 374. [Abstract] [Full Text] [PDF]

				Q. Liu and M. T. T. Wong-Riley Postnatal changes in cytochrome oxidase expressions in brain stem nuclei of rats: implications for sensitive periods J Appl Physiol, December 1, 2003; 95(6): 2285 - 2291. [Abstract] [Full Text]

				I. C. Solomon Focal CO2/H+ alters phrenic motor output response to chemical stimulation of cat pre-Botzinger complex in vivo J Appl Physiol, June 1, 2003; 94(6): 2151 - 2157. [Abstract] [Full Text] [PDF]

				Q. Liu, J. Kim, J. Cinotte, P. Homolka, and M. T. T. Wong-Riley Carotid body denervation effect on cytochrome oxidase activity in pre-Botzinger complex of developing rats J Appl Physiol, March 1, 2003; 94(3): 1115 - 1121. [Abstract] [Full Text] [PDF]

				I. C. Solomon Influence of respiratory network drive on phrenic motor output evoked by activation of cat pre-Botzinger complex Am J Physiol Regulatory Integrative Comp Physiol, February 1, 2003; 284(2): R455 - R466. [Abstract] [Full Text] [PDF]

				D. Mutolo, F. Bongianni, M. Carfi, and T. Pantaleo Respiratory changes induced by kainic acid lesions in rostral ventral respiratory group of rabbits Am J Physiol Regulatory Integrative Comp Physiol, July 1, 2002; 283(1): R227 - R242. [Abstract] [Full Text] [PDF]

				H. Wang, T. P. Germanson, and P. G. Guyenet Depressor and Tachypneic Responses to Chemical Stimulation of the Ventral Respiratory Group Are Reduced by Ablation of Neurokinin-1 Receptor-Expressing Neurons J. Neurosci., May 1, 2002; 22(9): 3755 - 3764. [Abstract] [Full Text] [PDF]

				P. G. Guyenet, C. P. Sevigny, M. C. Weston, and R. L. Stornetta Neurokinin-1 Receptor-Expressing Cells of the Ventral Respiratory Group Are Functionally Heterogeneous and Predominantly Glutamatergic J. Neurosci., May 1, 2002; 22(9): 3806 - 3816. [Abstract] [Full Text] [PDF]

				Y.-Y. Liu, G. Ju, and M. T. T. Wong-Riley Distribution and colocalization of neurotransmitters and receptors in the pre-Botzinger complex of rats J Appl Physiol, September 1, 2001; 91(3): 1387 - 1395. [Abstract] [Full Text] [PDF]

				P. G. Guyenet and H. Wang Pre-Botzinger Neurons With Preinspiratory Discharges "In Vivo" Express NK1 Receptors in the Rat J Neurophysiol, July 1, 2001; 86(1): 438 - 446. [Abstract] [Full Text] [PDF]

				Y.-Y. Liu and M. T. T. Wong-Riley Developmental study of cytochrome oxidase activity in the brain stem respiratory nuclei of postnatal rats J Appl Physiol, February 1, 2001; 90(2): 685 - 694. [Abstract] [Full Text] [PDF]

				M. Thoby-Brisson and J.-M. Ramirez Role of Inspiratory Pacemaker Neurons in Mediating the Hypoxic Response of the Respiratory Network In Vitro J. Neurosci., August 1, 2000; 20(15): 5858 - 5866. [Abstract] [Full Text] [PDF]

				I. C. Solomon, N. H. Edelman, and M. H. O'Neal III CO2/H+ chemoreception in the cat pre-Botzinger complex in vivo J Appl Physiol, June 1, 2000; 88(6): 1996 - 2007. [Abstract] [Full Text] [PDF]

				I. C. Solomon, N. H. Edelman, and J. A. Neubauer Pre-Botzinger Complex Functions as a Central Hypoxia Chemosensor for Respiration In Vivo J Neurophysiol, May 1, 2000; 83(5): 2854 - 2868. [Abstract] [Full Text] [PDF]

				M. Thoby-Brisson, P. Telgkamp, and J.-M. Ramirez The Role of the Hyperpolarization-Activated Current in Modulating Rhythmic Activity in the Isolated Respiratory Network of Mice J. Neurosci., April 15, 2000; 20(8): 2994 - 3005. [Abstract] [Full Text] [PDF]

				X. M. Shao and J. L. Feldman Acetylcholine Modulates Respiratory Pattern: Effects Mediated by M3-Like Receptors in PreBotzinger Complex Inspiratory Neurons J Neurophysiol, March 1, 2000; 83(3): 1243 - 1252. [Abstract] [Full Text] [PDF]

				I. C. Gibson and A. J. Berger Effect of Ethanol Upon Respiratory-Related Hypoglossal Nerve Output of Neonatal Rat Brain Stem Slices J Neurophysiol, January 1, 2000; 83(1): 333 - 342. [Abstract] [Full Text] [PDF]

				D. Mutolo, F. Bongianni, M. Carfi, and T. Pantaleo Respiratory responses to thyrotropin-releasing hormone microinjected into the rabbit medulla oblongata Am J Physiol Regulatory Integrative Comp Physiol, November 1, 1999; 277(5): R1331 - R1338. [Abstract] [Full Text] [PDF]

				R. J. Butera Jr., J. Rinzel, and J. C. Smith Models of Respiratory Rhythm Generation in the Pre-Botzinger Complex. II. Populations of Coupled Pacemaker Neurons J Neurophysiol, July 1, 1999; 82(1): 398 - 415. [Abstract] [Full Text] [PDF]

				G. Hilaire and B. Duron Maturation of the Mammalian Respiratory System Physiol Rev, April 1, 1999; 79(2): 325 - 360. [Abstract] [Full Text] [PDF]

				I. C. Solomon, N. H. Edelman, and J. A. Neubauer Patterns of Phrenic Motor Output Evoked by Chemical Stimulation of Neurons Located in the Pre-Botzinger Complex In Vivo J Neurophysiol, March 1, 1999; 81(3): 1150 - 1161. [Abstract] [Full Text] [PDF]

				S. CORNE, K. WEBSTER, G. MCGINN, W. ST.- JOHN, and M. YOUNES Medullary Metastasis Causing Impairment of Respiratory Pressure Output with Intact Respiratory Rhythm Am. J. Respir. Crit. Care Med., January 1, 1999; 159(1): 315 - 320. [Abstract] [Full Text]

				R. Shannon, D. M. Baekey, K. F. Morris, and B. G. Lindsey Ventrolateral medullary respiratory network and a model of cough motor pattern generation J Appl Physiol, June 1, 1998; 84(6): 2020 - 2035. [Abstract] [Full Text] [PDF]

				J. M. Ramirez, U.J.A. Quellmalz, and B. Wilken Developmental Changes in the Hypoxic Response of the Hypoglossus Respiratory Motor Output In Vitro J Neurophysiol, July 1, 1997; 78(1): 383 - 392. [Abstract] [Full Text] [PDF]

				X. M. Shao and J. L. Feldman Respiratory Rhythm Generation and Synaptic Inhibition of Expiratory Neurons in Pre-Botzinger Complex: Differential Roles of Glycinergic and GABAergic Neural Transmission J Neurophysiol, April 1, 1997; 77(4): 1853 - 1860. [Abstract] [Full Text] [PDF]

				I. A. Rybak, J. F. R. Paton, and J. S. Schwaber Modeling Neural Mechanisms for Genesis of Respiratory Rhythm and Pattern. II. Network Models of the Central Respiratory Pattern Generator J Neurophysiol, April 1, 1997; 77(4): 2007 - 2026. [Abstract] [Full Text] [PDF]

				P. M. Lalley, O. Pierrefiche, A. M. Bischoff, and D. W. Richter cAMP-Dependent Protein Kinase Modulates Expiratory Neurons In Vivo J Neurophysiol, March 1, 1997; 77(3): 1119 - 1131. [Abstract] [Full Text] [PDF]