Nattie EE, Li A (2003) Substance P-saporin lesions of NK1-receptor expressing neurons in the medullary raphe reduce central chemoreception in sleep and wakefulness. Neuroscience 2003 Abstracts 826.7. Society for Neuroscience, New Orleans, LA.
Summary: Breathing, especially in sleep, depends on a CO2-related drive that comes from central chemoreceptors. Many brainstem chemoreceptor sites contain NK1-receptor expressing neurons and cell specific killing of them at one site, the retrotrapezoid nucleus, by injection of substance P-saporin (SP-SAP)produces hypoventilation and reduced chemosensitivity (J. Physiol. 544.2: 603-616, 2002). Here we focus on the medullary raphe, a putative chemoreceptor site rich in NK1-receptor expressing neurons. We studied rats, instrumented with EEG and EMG electrodes for sleep determination, before and during the two weeks after placing two injections (0.1 pmole in 100 nl of SP-SAP) 1 mm apart in the medullary raphe. SP-SAP injections reduced the number of NK1 receptor expressing neurons by 53% compared to controls injected with IgG-SAP (P< 0.01, two-way ANOVA). Room air breathing was unaffected in sleep or wakefulness. The level of breathing during inhalation of 7% CO2 at 7 and 14 days was reduced by 13 and 22%, respectively, in NREM sleep (P < 0.01, two way ANOVA) and by 19 and 24%, respectively, in wakefulness (P < 0.01, two way ANOVA). Body temperature, resting metabolic rate, and sleep cycling were not significantly affected. These SP-SAP injections did not significantly reduce the number of medullary raphe serotonergic neurons as determined by TPOH immunoreactivity. We conclude that, as in the retrotrapezoid nucleus, NK1 receptor expressing neurons in the medullary raphe are involved in central chemoreception.
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