Stornetta RL, Takakura AC, Moreira TS, Mulkey DP, Bayliss DA, Guyenet PG (2007) Phox2b-expressing neurons of the retrotrapezoid nucleus (RTN) and central respiratory chemoreception in rats. Neuroscience 2007 Abstracts 230.9. Society for Neuroscience, San Diego, CA.
Summary: The RTN contains glutamatergic interneurons that are strongly activated by CO2 via acidification. These chemosensitive neurons are non-catecholaminergic and they express the transcription factor Phox2b. Although RTN chemoreceptors innervate selectively the brainstem regions that contain the respiratory rhythm and pattern generator (CPG), it is not yet clear whether these neurons drive inspiration or expiration, pump or airway muscles, autonomic circuits or all of the above. To determine whether RTN neurons drive inspiration, we examined whether their selective destruction modifies the CO2 sensitivity of the phrenic nerve discharge (PND) in anesthetized vagotomized rats. Using electrophysiological recordings in vivo and in slices, we found that the chemosensitive neurons of RTN express substance P receptors. We also found that these cells can be destroyed by local injection of a substance P agonist conjugated with saporin (SSP-SAP). The kill rate of RTN chemoreceptors was determined by counting the number of residual Phox2b-expressing non-catecholaminergic neurons present in this structure 15 days after toxin injection. Unilateral injection of 0.6 ng SSP-SAP destroyed 75% of the presumptive chemoreceptors on the injected side only. The lesion was selective because nearby neurons such as facial motoneurons, catecholaminergic and serotonergic cells were spared. SSP-SAP also spared the ventral respiratory column caudal to RTN except for a small amount of damage in the Bötzinger region closest to RTN. Unilateral lesion of the Phox2b-expressing neurons of RTN had no effect on PND and on respiratory chemoreception. However, in such rats, a single injection of the GABA-mimetic muscimol into the contralateral intact RTN instantly eliminated PND. After muscimol, PND did not usually reappear in the presence of hypercapnia up to 10% end-expiratory CO2. However, PND could typically be reactivated by strong stimulation of peripheral chemoreceptors which suggests that the respiratory oscillator had remained functional after muscimol. Unilateral injection of a lower dose of SSP-SAP (0.15 ng) had no effect on the Phox2b-expressing neurons of RTN. In such rats, unilateral injection of muscimol into the contralateral RTN had no detectable effect on PND and central chemoreception.
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