Holstege Breathing, Emotion and Evolution

1. Auflage 2014
ISBN: 978-0-444-63495-5
Verlag: Elsevier Science & Techn.
Format: EPUB
Kopierschutz: Adobe DRM (»Systemvoraussetzungen)

E-Book, Englisch, Band 212, 422 Seiten

Reihe: Progress in Brain Research

Respiration is one of the most basic motor activities crucial for survival of the individual. It is under total control of the central nervous system, which adjusts respiratory depth and frequency depending on the circumstances the individual finds itself. For this reason this volume not only reviews the basic control systems of respiration, located in the caudal brainstem, but also the higher brain regions, that change depth and frequency of respiration. Scientific knowledge of these systems is crucial for understanding the problems in the many patients suffering from respiratory failure. - This well-established international series examines major areas of basic and clinical research within neuroscience, as well as emerging subfields.

Autoren/Hrsg.

Holstege, Gert

Inhaltsverzeichnis

1;Front Cover;1
2;Breathing, Emotion and Evolution;4
3;Copyright;5
4;Contributors;6
5;Preface;12
6;Contents;14
7;Chapter 1: Physiological and pathophysiological interactions between the respiratory central pattern generator and the sympat;24
7.1;1. Introduction;25
7.2;2. Respiratory Modulation of Sympathetic Activity;25
7.3;3. Respiratory Baroreflex;28
7.4;4. Respiratory-sympathetic Chemoreflex;31
7.5;5. Chronic Intermittent Hypoxia;34
7.6;6. Unified Theoretical Framework for Respiratory-Sympathetic Coupling: Limitations and Perspectives;38
7.7;Acknowledgments;41
7.8;References;41
8;Chapter 2: Coupling of respiratory and sympathetic activities in rats submitted to chronic intermittent hypoxia;48
8.1;1. Sympathetic Nervous System and Its Interaction with the Respiratory Network;48
8.2;2. Central Mechanisms Underlying respiratory-sympathetic Coupling;51
8.3;3. Relevance of Respiratory-Sympathetic Coupling Dysfunctions to the Development of Systemic Hypertension;54
8.4;4. Perspectives;57
8.5;Acknowledgments;57
8.6;References;58
9;Chapter 3: Function and modulation of premotor brainstem parasympathetic cardiac neurons that control heart rate by hypoxia-,;62
9.1;1. Introduction;63
9.2;2. Autonomic Control of Cardiac Function;63
9.3;3. Responses to Hypoxia;64
9.4;4. Cardiovascular Regulation During Sleep;67
9.5;5. Cardiovascular Changes with sleep-related Diseases such as OSA;72
9.6;6. Conclusions;73
9.7;Acknowledgments;73
9.8;References;73
10;Chapter 4: Discharge properties of upper airway motor units during wakefulness and sleep;82
10.1;1. Introduction and Background;83
10.2;2. Upper Airway Muscle Recording and Analysis Techniques;84
10.3;3. Upper Airway Motor Unit Discharge Patterns;85
10.4;4. Manipulations of sleep-wake State and Respiratory Drive;87
10.5;5. Overview;94
10.6;References;96
11;Chapter 5: Effects of calcium (Ca2+) extrusion mechanisms on electrophysiological properties in a hypoglossal motoneuron: Ins;100
11.1;1. Introduction;101
11.2;2. Methods;103
11.3;3. Results;106
11.3.1;3.1. Ca2+ Extrusion Mechanisms;106
11.3.2;3.2. Addition of BK Channels-Type I Firing;107
11.3.3;3.3. Addition of Ca2+ Buffering-Type D Firing;108
11.3.4;3.4. Combining BK Channels and Ca2+ Buffering;111
11.3.5;3.5. Ca2+ Diffusion;111
11.4;4. Discussion;114
11.4.1;4.1. Ca2+ Extrusion Mechanisms;115
11.4.2;4.2. Stable Modification to Firing Frequency;116
11.4.3;4.3. Type I and D Firing Behaviors;116
11.4.4;4.4. Context-Dependent Properties;116
11.4.5;4.5. Putative Mechanistic Explanations of Behavior;117
11.4.6;4.6. Long-Term Linear Decay of Frequency;117
11.4.7;4.7. Conclusion;117
11.5;Acknowledgment;118
11.6;References;118
12;Chapter 6: Using a computational model to analyze the effects of firing frequency on synchrony of a network of gap junction-c;122
12.1;1. Introduction;123
12.2;2. Methods and Simulation Details;124
12.2.1;2.1. Simulations with Different Levels of Gap Junction Coupling Strength;126
12.3;3. Results;127
12.3.1;3.1. Influence of Changes in SK Conductance and Input Current on Firing Frequency;127
12.3.2;3.2. Influence of Firing Frequency on Network Synchrony;129
12.3.3;3.3. Influence of Coupling Strength Extremes on Synchrony;131
12.4;4. Discussion;131
12.5;References;133
13;Chapter 7: The physiological significance of postinspiration in respiratory control;136
13.1;1. Introduction;137
13.2;2. Postinspiration During Eupnea;138
13.2.1;2.1. A General Definition of Postinspiration in Mammals;138
13.2.2;2.2. Laryngeal Adductor Muscle Activation in Postinspiration Brakes Expiratory Airflow;139
13.2.3;2.3. Postinspiratory Activity in the Crural Diaphragm;139
13.2.4;2.4. State Dependency and Variable Expression of Eupneic Postinspiratory Laryngeal Adduction;141
13.3;3. Postinspiratory Activity During Breath-Holding and Expulsive Reflexes that Protect the Respiratory Tract;141
13.4;4. Postinspiratory Activity During Nonventilatory Behavior;142
13.4.1;4.1. Vocal Fold Tensioning is Essential for Vocalization;142
13.4.2;4.2. Swallowing is Associated with the Postinspiratory Phase;142
13.4.3;4.3. Postinspiration During Defecation, Retching, and Vomiting;143
13.5;5. Central Origins of Postinspiratory Motor Activity;143
13.5.1;5.1. Reflections on the Role of Postinspiratory Neurons in Respiratory Rhythm and Pattern Formation;144
13.6;6. Clinical Implications of Disturbances to Postinspiratory Control;145
13.7;7. Concluding Remarks and Outlook;146
13.8;References;147
14;Chapter 8: Expiration: Breathing's other face;154
14.1;1. How Air Breathing Evolved Is Still Debated;155
14.2;2. The Evolution of the Aspiration Pump Began with an Expiratory Pump;155
14.3;3. In the Ancestral Breathing Cycle, Inspiration Follows Expiration, Which Is in Turn Followed by Glottal Closure;156
14.4;4. The end-inspiratory Pause Is a Major Controlled Variable in the Cycle;157
14.5;5. The Phases of the Respiratory Cycle in Mammals Appear to Be Homologous to Those in Reptiles;159
14.6;6. The Postinspiratory Pause Is a Major Controlled Variable in the Cycle;160
14.7;7. The Occurrence of Active Expiration in Mammals;161
14.8;8. Control of Expiration;164
14.9;9. Presence of an Expiratory Rhythm Generator;164
14.10;10. Phylogeny of the Rhythm Generators;165
14.11;11. Summary;165
14.12;Acknowledgment;166
14.13;References;166
15;Chapter 9: The effects of head-up and head-down tilt on central respiratory chemoreflex loop gain tested by hyperoxic rebrea.;172
15.1;1. Introduction;173
15.1.1;1.1. Respiratory Chemoreceptors;173
15.1.2;1.2. Central Respiratory Chemoreceptors;174
15.1.3;1.3. Testing and Modeling the Central Chemoreflex;174
15.1.3.1;1.3.1. Hyperoxic Steady-State Methods;175
15.1.3.2;1.3.2. Hyperoxic Rebreathing Methods;175
15.1.4;1.4. Central Respiratory Chemoreflex Loop Gain;176
15.1.5;1.5. Controller Gain;177
15.1.6;1.6. Mixing Gain;178
15.1.7;1.7. Plant Gain;178
15.1.8;1.8. Tilt and Pulmonary Mechanics;178
15.1.9;1.9. Aim and Hypothesis;179
15.2;2. Methods;179
15.2.1;2.1. Subject Recruitment and Inclusion Criteria;179
15.2.2;2.2. Subject Instrumentation and Data Collection;180
15.2.3;2.3. Experimental Protocol;180
15.2.4;2.4. Data Analysis and Statistics;180
15.2.4.1;2.4.1. Baseline Data;180
15.2.4.2;2.4.2. Central Respiratory Chemoreflex in Response to Hyperoxic Rebreathing;180
15.2.4.3;2.4.3. Statistics;182
15.3;3. Results;182
15.3.1;3.1. Baseline Measurements;183
15.3.2;3.2. Respiratory Variables During Tilt and Hyperoxic Rebreathing;184
15.4;4. Discussion;184
15.4.1;4.1. Baseline Measures;185
15.4.2;4.2. Body Position and Central Chemoreflex Loop Gain;185
15.4.3;4.3. Critique of Methods;186
15.4.3.1;4.3.1. Hyperoxia and Prior Hyperventilation Duration;187
15.4.3.2;4.3.2. Analysis;188
15.4.4;4.4. Isolation of Plant Gain;188
15.4.5;4.5. Loop Gain Terminology;188
15.5;5. Conclusion;190
15.6;Acknowledgments;190
15.7;References;190
16;Chapter 10: The challenges of respiratory motor system recovery following cervical spinal cord injury;196
16.1;1. Cervical Spinal Cord Injury and the Deficit in Respiratory Motor Function;198
16.2;2. Organization of the Respiratory Motor Circuitry and the Crossed Phrenic Phenomenon;199
16.3;3. Modeling Respiratory Motor Function Following Cervical Spinal Cord Injury;201
16.3.1;3.1. Cervical Spinal Cord Injury;201
16.3.2;3.2. Acute Models of Cervical SCI and the Effect upon the Respiratory Motor System;202
16.3.3;3.3. Contusion and Chronic Models of Cervical SCI and the Affect upon the Respiratory Motor System;203
16.3.4;3.4. Endogenous Respiratory Motor System Recovery Following Subacute/Chronic Cervical Spinal Cord Injury;205
16.3.5;3.5. The Limitations of Spinal Cord Injury Models;206
16.4;4. Intrinsic Factors Controlling Respiratory Motor Recovery Following Cervical SCI;206
16.4.1;4.1. Adenosine A1 and c206
16.4.2;4.2. Gq Protein Signaling Cascades: Intermittent Hypoxia, 5-HT2, and Phrenic LTF;207
16.4.3;4.3. Gs Protein Signaling Cascade: Adenosine and 5-HT7;211
16.4.4;4.4. Optogenetics;212
16.5;5. Extrinsic Factors Controlling Respiratory Motor Recovery Following Cervical SCI;212
16.5.1;5.1. Inflammation;212
16.5.2;5.2. Grafting Tissue;214
16.5.3;5.3. Reduction of the Glial Scar;215
16.6;6. Future Directions: Integration of Treatment Strategies and Outcome Measures;217
16.6.1;6.1. Integration of Treatment Strategies;217
16.6.2;6.2. Assessment of Treatment Strategies Currently Overlooked in the Respiratory Motor System Model;219
16.6.3;6.3. Assessment of Multiple Outcome Measures;220
16.7;7. Concluding Remarks;220
16.8;Acknowledgments;221
16.9;References;221
17;Chapter 11: Intermittent hypoxia-induced respiratory long-term facilitation is dominated by enhanced burst frequency, not am.;244
17.1;1. Introduction;245
17.2;2. Methods;246
17.2.1;2.1. Animals;246
17.2.2;2.2. Experimental Protocol;246
17.2.3;2.3. Data Acquisition and Analysis;246
17.3;3. Results;247
17.3.1;3.1. Characteristics of EMGdia Activity Under BL Conditions and During Exposure to CO2 and a Single Bout of Acute Hypoxia;247
17.3.2;3.2. Response to AIH Trials;248
17.3.3;3.3. Response Following AIH Trials;249
17.4;4. Discussion;253
17.5;References;256
18;Chapter 12: Chronic nitric oxide synthase inhibition does not impair upper airway muscle adaptation to chronic intermittent h;260
18.1;1. Introduction;261
18.2;2. Methods;262
18.2.1;2.1. Chronic Intermittent Hypoxia;262
18.2.2;2.2. Experimental Procedure;263
18.2.3;2.3. Protocol;263
18.2.4;2.4. MHC Fiber Typing;264
18.2.5;2.5. Image Capture and Analysis;264
18.2.6;2.6. Data Analysis;265
18.3;3. Results;265
18.3.1;3.1. Body Mass and Hematocrit;265
18.3.2;3.2. Peak Force;265
18.3.3;3.3. Force-Frequency Relationship;265
18.3.4;3.4. Fatigue Index;266
18.3.5;3.5. MHC Fiber Type;266
18.4;4. Discussion;267
18.5;Acknowledgment;271
18.6;References;271
19;Chapter 13: The generation of pharyngeal phase of swallow and its coordination with breathing: Interaction between the swallo;276
19.1;1. Introduction;277
19.1.1;1.1. Definition of Swallow;277
19.1.2;1.2. Experimental Provocation of Swallow;278
19.1.3;1.3. The Swallow CPG;278
19.1.3.1;1.3.1. Dorsal Swallowing Group;279
19.1.3.2;1.3.2. Ventral Swallowing Group;280
19.2;2. Swallow and Breathing Coordination: ``Safe Swallows´´;281
19.2.1;2.1. Swallow Initiation in Specific Phases of the Respiratory Cycle;281
19.2.2;2.2. Arrest of Respiratory Airflow During Swallow: ``Swallow-Apnea´´;282
19.2.3;2.3. Expiration and Phase Resetting Following Swallow;282
19.3;3. Interaction Between Swallow and Respiratory CPGs Enabling Swallowing and Breathing Coordination;283
19.3.1;3.1. Gating of Swallow Initiation in Specific Phases of the Respiratory Cycle;285
19.3.2;3.2. Laryngeal Adduction During Swallow;287
19.3.3;3.3. Minimized Breathing Movements During Swallow: ``Swallow-Breath´´;287
19.3.4;3.4. Respiratory Phase Resetting Following Swallows;289
19.4;4. Summary and Perspectives;290
19.5;References;292
20;Chapter 14: Control of coughing by medullary raphé;300
20.1;1. Introduction;300
20.2;2. Raphé Neurons and Respiratory Control;302
20.3;3. Raphé Neurons Control of Coughing and Other Reflex Behaviors;303
20.3.1;3.1. Resumé;303
20.3.2;3.2. Methodology;305
20.3.3;3.3. Reflex Responses Strength Control;306
20.3.4;3.4. Motor Pattern of Reflex Response;309
20.4;4. Concluding Remarks;311
20.5;Acknowledgment;312
20.6;References;312
21;Chapter 15: The respiratory-vocal system of songbirds: Anatomy, physiology, and neural control;320
21.1;1. Introduction;321
21.2;2. Peripheral Mechanics of Breathing in (Song)birds;322
21.2.1;2.1. Lungs;322
21.2.2;2.2. Air Sacs and Respiratory Muscles;324
21.2.3;2.3. Syrinx;327
21.2.4;2.4. Upper Vocal Tract;330
21.2.5;2.5. Chemoreceptors;331
21.3;3. Central Organization of Respiratory-Related Neurons;331
21.3.1;3.1. Respiratory Muscle Motoneurons;331
21.3.2;3.2. Organization of Respiratory-Related Neurons in the Brainstem;332
21.3.3;3.3. Respiratory-Vocal Circuitry;334
21.3.4;3.4. Physiological Properties of Hindbrain Respiratory Neurons in Songbirds;335
21.4;4. Linking the ``song System´´ to the Vocal-respiratory Hindbrain;338
21.4.1;4.1. Functional Organization of the Song Motor Pathway;338
21.4.2;4.2. A Sparse Neural Code for Song;340
21.4.3;4.3. HVC and Its Control of Respiratory Timing During Song;342
21.4.4;4.4. The Song System Provides Direct Drive to the Respiratory System;343
21.5;5. Song Production and the ``respiratory-thalamo-cortical´´ Pathway;344
21.5.1;5.1. The ``Respiratory-Thalamic´´ Pathway is Necessary for Song;344
21.5.2;5.2. A Role for the Respiratory System in Hemispheric Coordination;346
21.5.3;5.3. Neural Properties of the Respiratory-Thalamic Pathway;346
21.5.4;5.4. Integrating the Respiratory System with Song Control;347
21.6;6. Concluding Remarks;350
21.7;Acknowledgments;350
21.8;References;350
22;Chapter 16: The lamprey blueprint of the mammalian nervous system;360
22.1;1. The Motor Infrastructure;361
22.1.1;1.1. The Brainstem-Spinal Cord Control of Locomotion;361
22.1.2;1.2. Respiratory Control;361
22.1.3;1.3. The Control of Eye, Orienting, and Evasive Motor Behavior in the Optic Tectum/Superior Colliculus;363
22.1.4;1.4. General Comments on the Motor Infrastructure;363
22.2;2. The Forebrain Control of the Brainstem-Spinal Cord Motor Programs;363
22.2.1;2.1. The Control of Dopamine Neurons from the Lateral Habenulae;367
22.2.2;2.2. Pallium and the Layered Neocortex;368
22.3;3. Conclusion;369
22.4;Acknowledgments;369
22.5;References;369
23;Chapter 17: The midbrain periaqueductal gray changes the eupneic respiratory rhythm into a breathing pattern necessary for s.;374
23.1;1. Introduction;375
23.2;2. Functional Segregation Within the PAG;376
23.3;3. The PAG Connectome;377
23.4;4. PAG integrates Respiratory Responses;380
23.5;5. PAG-induced Respiratory Patterning;382
23.5.1;5.1. PAGdm Generates Slow and Deep Breathing;383
23.5.2;5.2. PAGdl Generates Tachypnea;384
23.5.3;5.3. PAGl Generates Inspiratory Apneusis;384
23.5.4;5.4. PAGvl Generates Breath Hold;384
23.5.5;5.5. PAGvl Generates Irregular Breathing and Apnea;386
23.6;6. Vocalization: A Modified Form of Breathing;387
23.7;7. PAG Control of the Crural and Costal Diaphragm;389
23.8;8. PAG Control of Intra-abdominal Pressure;389
23.9;9. PAG Control of Medullary Respiratory Neurons;391
23.9.1;9.1. PAG Modulates the Activity of Medullary Late-I and Post-I Neurons;391
23.9.2;9.2. PAG Modulates the Pre-I Neurons in the Pre-Bötzinger Complex Phasically and Tonically, As Well As Silences Them When Re.;393
23.10;10. Hypothalamic Mediation of Dorsal PAG-induced Respiratory Effect;394
23.11;11. Pharmacology of PAG-Induced Respiratory Modulation;395
23.12;12. PAG, Serotonin, and Level-Setting Systems;395
23.13;13. Chemosensory, Upper Airway, and Pulmonary Afferent Information to the PAG;397
23.14;14. Amygdala-PAG Interactions;398
23.15;15. Breathing and the PAG: Therapeutic Targets for the Treatment of Emotional and Psychiatric Disorders;399
23.16;16. Conclusion;399
23.17;Acknowledgment;401
23.18;References;401
24;Index;408
25;Other volumes in Progress in Brain Research;420

Leseproben

Chapter 1 Physiological and pathophysiological interactions between the respiratory central pattern generator and the sympathetic nervous system
Yaroslav I. Molkov*,1; Daniel B. Zoccal†; David M. Baekey‡; Ana P.L. Abdala§; Benedito H. Machado¶; Thomas E. Dick||; Julian F.R. Paton§; Ilya A. Rybak#    * Department of Mathematical Sciences, Indiana University—Purdue University Indianapolis, IN, USA
† Department of Physiology and Pathology, Dentistry School of Araraquara, São Paulo State University, Araraquara, São Paulo, Brazil
‡ Department of Physiological Sciences, University of Florida, Gainesville, FL, USA
§ School of Physiology and Pharmacology, Bristol Heart Institute, University of Bristol, Bristol, UK
¶ Department of Physiology, School of Medicine of Ribeirão Preto, University of São Paulo, Ribeirão Preto, São Paulo, Brazil
|| Departments of Medicine and Neurosciences, Case Western Reserve University, Cleveland, OH, USA
# Department of Neurobiology and Anatomy, Drexel University College of Medicine, Philadelphia, PA, USA
1 Corresponding author: Tel.: + 1-317-274-6934; Fax: + 1-317-274-3460 email address: [e-mail] Abstract
Respiratory modulation seen in the sympathetic nerve activity (SNA) implies that the respiratory and sympathetic networks interact. During hypertension elicited by chronic intermittent hypoxia (CIH), the SNA displays an enhanced respiratory modulation reflecting strengthened interactions between the networks. In this chapter, we review a series of experimental and modeling studies that help elucidate possible mechanisms of sympatho-respiratory coupling. We conclude that this coupling significantly contributes to both the sympathetic baroreflex and the augmented sympathetic activity after exposure to CIH. This conclusion is based on the following findings. (1) Baroreceptor activation results in perturbation of the respiratory pattern via transient activation of postinspiratory neurons in the Bötzinger complex (BötC). The same BötC neurons are involved in the respiratory modulation of SNA, and hence provide an additional pathway for the sympathetic baroreflex. (2) Under hypercapnia, phasic activation of abdominal motor nerves (AbN) is accompanied by synchronous discharges in SNA due to the common source of this rhythmic activity in the retrotrapezoid nucleus (RTN). CIH conditioning increases the CO2 sensitivity of central chemoreceptors in the RTN which results in the emergence of AbN and SNA discharges under normocapnic conditions similar to those observed during hypercapnia in naïve animals. Thus, respiratory–sympathetic interactions play an important role in defining sympathetic output and significantly contribute to the sympathetic activity and hypertension under certain physiological or pathophysiological conditions, and the theoretical framework presented may be instrumental in understanding of malfunctioning control of sympathetic activity in a variety of disease states. Keywords respiratory–sympathetic interactions baroreflex chronic intermittent hypoxia hypertension modeling 1 Introduction
The respiratory rhythm and sympathetic activity are generated centrally within the brainstem. Neuronal circuits that generate and modulate respiratory and sympathetic activities appear to interact and this interaction depends on various sensory afferents (Gilbey, 2007). Here, we review possible respiratory–sympathetic interactions proposed in our recent experimental and modeling studies. These hypothetical interactions are used to explain the mechanisms of the respiratory modulation seen in sympathetic output (Section 2); the changes in the respiratory patterns due to baroreceptor stimulation (Section 3); the changes in the patterns of respiratory-modulated sympathetic activity (Section 4); and the plasticity seen within brainstem respiratory–sympathetic networks in an animal model of sleep apnea (Section 5). Finally, we discuss the limitations and perspectives of the proposed theoretical framework. 2 Respiratory Modulation of Sympathetic Activity
The respiratory rhythm and coordinated motor pattern is provided by a respiratory central pattern generator (CPG) located in the lower brainstem (Bianchi et al., 1995; Cohen, 1979; Lumsden, 1923). The pre-Bötzinger complex (pre-BötC), located within the medullary ventral respiratory column (VRC) is considered a major source of rhythmic inspiratory activity (Koshiya and Smith, 1999; Paton, 1996; Rekling and Feldman, 1998; Smith et al., 1991). The pre-BötC, interacting with the adjacent Bötzinger complex (BötC) containing mostly expiratory neurons (Ezure, 1990; Ezure et al., 2003; Jiang and Lipski, 1990; Tian et al., 1999) represents a core of the respiratory CPG (Bianchi et al., 1995; Richter, 1996; Richter and Spyer, 2001; Rybak et al., 2004, 2007, 2008; Smith et al., 2007, 2009, 2012; Tian et al., 1999). This core circuitry generates primary respiratory oscillations defined by the intrinsic biophysical properties of respiratory neurons involved, the architecture of network interactions between respiratory neural populations within and between the pre-BötC and BötC, and inputs from other brainstem compartments, including the pons, retrotrapezoid nucleus (RTN), raphé, and nucleus tractus solitarii (NTS) (Smith et al., 2012). The sympathetic nerve activity (SNA) was shown to display respiratory modulation that persisted after vagotomy and decerebration (Adrian et al., 1932; Barman and Gebber, 1980; Habler et al., 1994; Haselton and Guyenet, 1989; Richter and Spyer, 1990; Simms et al., 2009) supporting the idea of a coupling between brainstem respiratory and sympathetic networks. This coupling may represent an important mechanism for coordination of minute ventilation and vasoconstriction/dilation aimed at increasing the efficiency of oxygen uptake/perfusion at rest, and at boosting vasomotion and assisting with perfusion of tissues for maintaining homeostasis during metabolic challenges (Zoccal et al., 2009b). Recent modeling studies also suggest improved efficiency of cardiac function provided by respiratory–sympathetic interactions (Ben-Tal, 2012; Ben-Tal et al., 2012). Therefore, the respiratory modulation may represent a considerable factor contributing to the dynamic control of SNA. Under baseline conditions (normoxia/normocapnia) SNA usually exhibits positive modulation during inspiration (Fig. 1, upper traces) (Baekey et al., 2008; Malpas, 1998, 2010; Simms et al., 2010; Zoccal et al., 2008, 2009a,b). It has been suggested that this modulation results from specific interactions between respiratory and sympathetic neurons at the level of ventrolateral medulla, where many of the neurons involved in the generation of respiratory and sympathetic activities are located (Habler et al., 1994; Haselton and Guyenet, 1989; Koshiya and Guyenet, 1996; McAllen, 1987; Richter and Spyer, 1990; Zhong et al., 1997). Specifically in this region, the inspiratory and expiratory neurons of the VRC interact with the presympathetic neurons of the rostral ventrolateral medulla (RVLM) as well as with GABAergic interneurons of caudal ventrolateral medulla (CVLM) inhibiting RVLM neurons (Haselton and Guyenet, 1989; Mandel and Schreihofer, 2006; Richter and Spyer, 1990; Sun et al., 1997). It appears that the pons may play a critical role in these interactions. Ponto-medullary transections in situ were shown to significantly reduce or even eliminate the respiratory modulation of SNA (Fig. 1, “after transection”, see also Baekey et al., 2008). This suggests that pontine projections to medullary respiratory and sympathetic neurons are crucial for the respiratory–sympathetic coupling. Accordingly, pontine neurons may have a direct effect on the activity of presympathetic RVLM neurons or they may act indirectly through respiratory neurons in the VRC (Fig. 2A, blue dashed arrows). Figure 1 Thoracic sympathetic (thSNA) and phrenic (PNA) nerve activities before and after ponto-medullary transection. Before transection (intact pons), thSNA has a clear respiratory modulation which is attenuated or eliminated after transection. Figure 2 (A) Conceptual model of interaction between respiratory-related activity of the ventral respiratory column (VRC), pontine circuits (PONS), sensory network in the nucleus tractus solitary (NTS), and rostral and caudal ventrolateral medulla (RVLM/CVLM). Dotted arrows represent the effects of VRC and PONS on RVLM providing respiratory modulation of SNA. The sympathetic baroreceptor reflex operates via two pathways (red (gray in the print version) solid arrows): one direct pathway includes baroreceptors, 2nd-order barosensitive cells (Baro) in...