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0065 Serotonergic Dorsal Raphe Neurons and the Neuronal Circuit for the Hypercapnia Induced Arousal

Kaur, S ; Khanday, M A ; Bandaru, S S ; Todd, W ; Fuller, P M ; Saper, C B

Sleep (New York, N.Y.), 2018-04, Vol.41 (suppl_1), p.A27-A27 [Periódico revisado por pares]

US: Oxford University Press

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  • Título:
    0065 Serotonergic Dorsal Raphe Neurons and the Neuronal Circuit for the Hypercapnia Induced Arousal
  • Autor: Kaur, S ; Khanday, M A ; Bandaru, S S ; Todd, W ; Fuller, P M ; Saper, C B
  • Assuntos: Lasers
  • É parte de: Sleep (New York, N.Y.), 2018-04, Vol.41 (suppl_1), p.A27-A27
  • Descrição: Abstract Introduction Serotoninergic dorsal (DRSert) and medullary raphe neurons are CO2 responsive, and mice lacking these neurons have impaired arousal to CO2. However, CO2 responsiveness can be restored by a 5HT2A agonist, suggesting that they are modulatory. Recently, we showed that the external lateral parabrachial nucleus containing calcitonin gene related peptide (PBelCGRP) are required for hypercapnia-induced arousal. PBelCGRP neurons also receive serotoninergic innervation from the DRSert. We therefore hypothesize that DRsert neurons mediate CO2 arousal by its input to the PBel. Methods We used serotonin transporter (Sert)-Cre mice to test the effect of optogenetic inhibition of DRSert neurons in CO2 arousal. We injected AAV-FLEX-ArchT and implanted optical fiber into DR of Sert-Cre mice. A separate set of mice were injected in DR with AAV-FLEX-ArchT and implanted with optical fibers in the PBel for terminal inhibition to test whether DRsert mediate CO2 arousals by its input to the PBel. All mice were instrumented for sleep and optogenetics and were tested for EEG arousals to 10% CO2. Arousal Latencies were compared with optogenetic inhibition for either the neurons or the terminals in the same mice with and without laser light. Lastly, we also selectively deleted DRSert neurons in Sert-Cre mice with AAV-FLEX-DTA, and arousal latency was compared between the mice with and without cell deletions. Results In optogenetics experiments, with laser-OFF, mice showed an arousal latency of 13.8 ± 0.7 sec, and woke-up on every CO2 trial. While, DRsert inhibition with laser-ON (n=6) and in DRsert deletions experiments (n=6), arousal latency to CO2 tripled to 40.9 ± 6.4 sec and 39.6 ± 2.5 sec, with no arousal in 21.2% and in 17.6% of trials respectively. Similarly, optogenetic inhibition of DRsert terminals in the PBel (n=3) also produced arousal latency of 37.7 ± 1.7 sec, with no arousal to CO2 in 13% of the trials. Conclusion DRsert neurons are important part of the neural circuitry regulating the cortical EEG arousals to hypercapnia, and that this is mediated entirely by its projections to the PBel neurons. Support (If Any) NIH- 2P01 HL095491.
  • Editor: US: Oxford University Press
  • Idioma: Inglês
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