Rhythmic Breathing Control: The Ventrolateral Medulla
The ventrolateral medulla, specifically the preBötzinger complex (preBötC), is the primary site responsible for generating the rhythmic breathing cycle in mammals. 1
Primary Rhythm Generator
The preBötC serves as the essential rhythm-generating network for inspiration and has been demonstrated to be both necessary and sufficient for generating inspiratory rhythm. 2 This region contains spontaneously bursting neurons that form the core oscillatory mechanism driving the breathing cycle. 3
Distributed Brainstem Network
While the preBötC is the primary generator, rhythmic breathing emerges through interactions between multiple anatomically distinct networks:
The ventrolateral medulla contains the central pattern generator (CPG) that produces the basic respiratory rhythm and coordinates motor output to respiratory muscles 1
The raphe nuclei and pons contribute to controlling the duration and magnitude of respiratory phases, working in concert with the ventrolateral medulla 1
The nucleus tractus solitarius (nTS) processes vagal sensory afferent information from the airways and lungs, providing critical feedback that modulates the rhythm generator 1
Triple Oscillator Mechanism
Current evidence supports a "triple oscillator" model where three distinct medullary networks generate the three phases of breathing:
- Inspiration: Generated by the preBötzinger complex 2, 4
- Post-inspiration: Generated by the post-inspiratory complex (PiCo) 2
- Active expiration: Generated by the lateral parafacial nucleus/retrotrapezoid nucleus (pFL/RTN) 2, 4
Network vs. Pacemaker Mechanisms
The respiratory rhythm can be generated through both network mechanisms (requiring inhibitory synaptic transmission between neurons) and pacemaker mechanisms (individual neurons with intrinsic bursting properties). 3, 5 This dual capability provides robustness—the system continues functioning even when one mechanism is compromised. 3
Clinical Relevance
Understanding this distributed network is essential because:
No single "respiratory center" exists—the rhythm emerges from interactions between multiple brainstem regions 1, 5
The system is remarkably robust due to multiple levels of rhythm-generating capability, allowing breathing to persist despite various insults 3, 5
Higher brain regions (cortex, limbic system) can voluntarily override or modulate the automatic brainstem rhythm, explaining why breathing can be consciously controlled 1