Respiratory plasticity

Respiratory plasticity is not a single molecular target but rather a persistent change in the neural control of breathing based on prior experience or environmental stimuli, most notably induced by acute intermittent hypoxia (AIH). This physiological phenomenon involves long-lasting increases in respiratory motor output, such as phrenic long-term facilitation (pLTF), and is mediated by a complex network of signaling molecules in the brainstem and spinal cord [Mitchell & Johnson, 2003, PMID: 14514515]. Key molecular players include serotonin (5-HT) receptors, adenosine receptors, and the Brain-Derived Neurotrophic Factor (BDNF)/TrkB signaling pathway, which facilitate synaptic transmission to motor neurons [Dale-Nagle et al., 2010, PMID: 20624844]. From a therapeutic perspective, manipulating respiratory plasticity is a major area of research for treating respiratory insufficiency in conditions like spinal cord injury (SCI), amyotrophic lateral sclerosis (ALS), and sleep apnea [Feldman et al., 2003, PMID: 12511674]. Pharmacological agents such as selective serotonin reuptake inhibitors (SSRIs) or ampakines are utilized or investigated to enhance these endogenous plastic mechanisms and improve ventilatory capacity [Devinney et al., 2013, PMID: 23624610].

Other names

Neural plasticity of the respiratory systemLong-term facilitation (LTF)Phrenic long-term facilitation (pLTF)Ventilatory long-term facilitationHypoxia-induced respiratory plasticity

Modulation of respiratory plasticity occurs through the activation of signaling cascades—primarily the 'Q pathway' (serotonin-dependent) and the 'S pathway' (adenosine-dependent)—which increase the synthesis and release of Brain-Derived Neurotrophic Factor (BDNF) and enhance TrkB receptor signaling to strengthen synaptic inputs to phrenic motor neurons.