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.jpg): Failed to open stream: No such file or directory in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 117 Am+J+Respir+Crit+Care+Med
2014 ; 190
(11
): 1301-10
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Optogenetic stimulation of adrenergic C1 neurons causes sleep state-dependent
cardiorespiratory stimulation and arousal with sighs in rats
#MMPMID25325789
Am J Respir Crit Care Med
2014[Dec]; 190
(11
): 1301-10
PMID25325789
show ga
RATIONALE: The rostral ventrolateral medulla (RVLM) contains central respiratory
chemoreceptors (retrotrapezoid nucleus, RTN) and the sympathoexcitatory,
hypoxia-responsive C1 neurons. Simultaneous optogenetic stimulation of these
neurons produces vigorous cardiorespiratory stimulation, sighing, and arousal
from non-REM sleep. OBJECTIVES: To identify the effects that result from
selectively stimulating C1 cells. METHODS: A Cre-dependent vector expressing
channelrhodopsin 2 (ChR2) fused with enhanced yellow fluorescent protein or
mCherry was injected into the RVLM of tyrosine hydroxylase (TH)-Cre rats. The
response of ChR2-transduced neurons to light was examined in anesthetized rats.
ChR2-transduced C1 neurons were photoactivated in conscious rats while EEG, neck
muscle EMG, blood pressure (BP), and breathing were recorded. MEASUREMENTS AND
MAIN RESULTS: Most ChR2-expressing neurons (95%) contained C1 neuron markers and
innervated the spinal cord. RTN neurons were not transduced. While the rats were
under anesthesia, the C1 cells were faithfully activated by each light pulse up
to 40 Hz. During quiet resting and non-REM sleep, C1 cell stimulation (20 s, 2-20
Hz) increased BP and respiratory frequency and produced sighs and arousal from
non-REM sleep. Arousal was frequency-dependent (85% probability at 20 Hz).
Stimulation during REM sleep increased BP, but had no effect on EEG or breathing.
C1 cell-mediated breathing stimulation was occluded by hypoxia (12% FIO2), but
was unchanged by 6% FiCO2. CONCLUSIONS: C1 cell stimulation reproduces most
effects of acute hypoxia, specifically cardiorespiratory stimulation, sighs, and
arousal. C1 cell activation likely contributes to the sleep disruption and
adverse autonomic consequences of sleep apnea. During hypoxia (awake) or REM
sleep, C1 cell stimulation increases BP but no longer stimulates breathing.