The article reviews recent progress in understanding the three critical aspects of breathing: rhythmicity, plasticity, and chemosensitivity. 1. **Rhythmicity**: The preBötzinger Complex (preBötC) is identified as a critical site for respiratory rhythm generation, though the role of pacemaker neurons is less clear. Recent studies suggest that coupled oscillators may also play a role. Lesions to preBötC neurons can severely disrupt breathing patterns, but the absence of clear anatomical markers for these neurons has led to ongoing debate about their exact function. 2. **Plasticity**: Breathing exhibits significant plasticity in response to various stimuli, including hypoxia, hypercapnia, and stress. Serotonin-dependent long-term facilitation following intermittent hypoxia is a key example of this plasticity. The mechanisms involve serotonin receptor activation, which is necessary for induction but not maintenance of the effect. The model suggests that serotonin released by raphe neurons acts within respiratory motor nuclei to initiate pattern-sensitive cellular and synaptic events that underlie long-term facilitation. 3. **Chemosensitivity**: Central chemoreceptors, located in the brainstem, are essential for sensing CO2 and pH levels to regulate breathing. These receptors are distributed across multiple brain regions, including the nucleus tractus solitarius, locus ceruleus, and medullary raphe. Chemosensitive neurons may also be responsive to changes in blood pH or CO2 produced during a breath. The presence of chemosensitive neurons at multiple sites suggests a hierarchical organization, possibly reflecting evolutionary adaptations. The article also discusses the clinical significance of these findings, particularly in conditions like Sudden Infant Death Syndrome (SIDS) and sleep-disordered breathing, where defects in respiratory control mechanisms can lead to critical health issues.The article reviews recent progress in understanding the three critical aspects of breathing: rhythmicity, plasticity, and chemosensitivity. 1. **Rhythmicity**: The preBötzinger Complex (preBötC) is identified as a critical site for respiratory rhythm generation, though the role of pacemaker neurons is less clear. Recent studies suggest that coupled oscillators may also play a role. Lesions to preBötC neurons can severely disrupt breathing patterns, but the absence of clear anatomical markers for these neurons has led to ongoing debate about their exact function. 2. **Plasticity**: Breathing exhibits significant plasticity in response to various stimuli, including hypoxia, hypercapnia, and stress. Serotonin-dependent long-term facilitation following intermittent hypoxia is a key example of this plasticity. The mechanisms involve serotonin receptor activation, which is necessary for induction but not maintenance of the effect. The model suggests that serotonin released by raphe neurons acts within respiratory motor nuclei to initiate pattern-sensitive cellular and synaptic events that underlie long-term facilitation. 3. **Chemosensitivity**: Central chemoreceptors, located in the brainstem, are essential for sensing CO2 and pH levels to regulate breathing. These receptors are distributed across multiple brain regions, including the nucleus tractus solitarius, locus ceruleus, and medullary raphe. Chemosensitive neurons may also be responsive to changes in blood pH or CO2 produced during a breath. The presence of chemosensitive neurons at multiple sites suggests a hierarchical organization, possibly reflecting evolutionary adaptations. The article also discusses the clinical significance of these findings, particularly in conditions like Sudden Infant Death Syndrome (SIDS) and sleep-disordered breathing, where defects in respiratory control mechanisms can lead to critical health issues.