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Cholinergic modulation of pedunculopontine tegmental nucleus in respiratory control

The pedunculopontine tegmental nucleus (PPTn) has been shown to have important functions relevant to the regulation of behavioral states and various motor control systems, including breathing control. The PPTn is considered an important nucleus in the mesopontine region with considerably cholinergic input to the ventral respiratory column. In addition, recent studies indicate that cholinergic innervation of the ventral respiratory column may play an important role in modulation of breathing. Here, we investigated a cholinergic projection from the PPTn to the retrotrapezoid nucleus (RTN) and if the stimulation of cholinergic neurons in the PPTn elicit changes in the respiratory pattern in conscious rats. Male Wistar rats (280–350g, N = 3–7/group) with unilateral stainless steel cannula implanted into the PPTn were used. Respiratory parameters (tidal volume (VT), respiratory frequency (fR) and ventilation (VE)) were analyzed by whole body pletismography. Retrograde tracer FluorGold (FG‐2%) injected into the RTN region showed a light direct cholinergic projection from PPTn to RTN. In unrestrained awake rats, unilateral injection of the cholinergic muscarinic agonist carbachol (10 mM − 100 nL) in the PPTn decreased fR (60 ± 8, vs. saline: 102 ± 8 breaths/min) and VE (315 ± 105, vs. saline: 604 ± 114 ml/kg/min), without changing VT. We conclude that cholinergic stimulation of PPTn has a significant impact on the breathing activity. Our data suggest that PPTn may influence breathing through a direct pathway from the mesopontine region to the RTN.