A novel excitatory network for the control of breathing

• Published in: Nature (London) Vol. 536; no. 7614; pp. 76 - 80
• Main Authors: Anderson, Tatiana M., Garcia, Alfredo J., Baertsch, Nathan A., Pollak, Julia, Bloom, Jacob C., Wei, Aguan D., Rai, Karan G., Ramirez, Jan-Marino
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 04.08.2016; Nature Publishing Group
• Subjects: 13/1; 13/51; 14/19; 631/378/2632; 631/378/2632/2633; 631/378/3920; 64/110; 9/30; 9/74; Alzheimer's disease; Analysis; Animals; Cholinergic Neurons - metabolism; Dementia disorders; Female; GABA; gamma-Aminobutyric Acid - metabolism; Glutamine - metabolism; Humanities and Social Sciences; letter; Male; Mice; multidisciplinary; Neural Inhibition - physiology; Neural networks; Neural Pathways - cytology; Neural Pathways - physiology; Neurophysiology; Parkinson's disease; Physiological aspects; Respiration; Respiratory Center - anatomy & histology; Respiratory Center - cytology; Respiratory Center - physiology; Rodents; Science; Synapses - metabolism; Time Factors; United States
• ISSN: 0028-0836; 1476-4687
• DOI: 10.1038/nature18944

A novel rhythmogenic brainstem network was discovered in mice that is necessary and sufficient for generating postinspiration, a breathing phase also used for swallowing, coughing and vocalization. Brainstem generation of postinspiratory activity Vocalization, swallowing and coughing occur after breathing in a phase called postinspiration. Here, Jan-Marino Ramirez and colleagues describe a previously unknown excitatory circuit that drives postinspiratory activity. While classical excitatory neurons provide the drive in the network, inhibitory neurons establish the timing and ensure that postinspiratory epochs are coordinated with inspiration. Breathing must be tightly coordinated with other behaviours such as vocalization, swallowing, and coughing. These behaviours occur after inspiration, during a respiratory phase termed postinspiration 1 . Failure to coordinate postinspiration with inspiration can result in aspiration pneumonia, the leading cause of death in Alzheimer’s disease, Parkinson’s disease, dementia, and other neurodegenerative diseases 2 . Here we describe an excitatory network that generates the neuronal correlate of postinspiratory activity in mice. Glutamatergic–cholinergic neurons form the basis of this network, and GABA (γ-aminobutyric acid)-mediated inhibition establishes the timing and coordination relative to inspiration. We refer to this network as the postinspiratory complex (PiCo). The PiCo has autonomous rhythm-generating properties and is necessary and sufficient for postinspiratory activity in vivo . The PiCo also shows distinct responses to neuromodulators when compared to other excitatory brainstem networks. On the basis of the discovery of the PiCo, we propose that each of the three phases of breathing is generated by a distinct excitatory network: the preBötzinger complex, which has been linked to inspiration 3 , 4 ; the PiCo, as described here for the neuronal control of postinspiration; and the lateral parafacial region (pF L ), which has been associated with active expiration, a respiratory phase that is recruited during high metabolic demand 4 , 5 .