Atropine microdialysis within or near the pre-Botzinger Complex increases breathing frequency more during wakefulness than during NREM sleep. J Appl Physiol (1985) 2013 Mar 01;114(5):694-704
Date
12/29/2012Pubmed ID
23271698Pubmed Central ID
PMC3615593DOI
10.1152/japplphysiol.00634.2012Scopus ID
2-s2.0-84878620405 (requires institutional sign-in at Scopus site) 15 CitationsAbstract
Normal activity of neurons within the medullary ventral respiratory column (VRC) in or near the pre-Bötzinger Complex (preBötC) is dependent on the balance of inhibitory and excitatory neuromodulators acting at their respective receptors. The role of cholinergic neuromodulation during awake and sleep states is unknown. Accordingly, our objective herein was to test the hypotheses that attenuation of cholinergic modulation of VRC/preBötC neurons in vivo with atropine would: 1) decrease breathing frequency more while awake than during non-rapid-eye-movement (NREM) sleep and 2) increase other excitatory neuromodulators. To test these hypotheses, we unilaterally dialyzed mock cerebrospinal fluid (mCSF) or 50 mM atropine in mCSF in or near the preBötC region of adult goats during the awake (n = 9) and NREM sleep (n = 7) states. Breathing was monitored, and effluent dialysate was collected for analysis of multiple neurochemicals. Compared with dialysis of mCSF alone, atropine increased (P < 0.05) breathing frequency while awake during the day [+10 breaths (br)/min] and at night (+9 br/min) and, to a lesser extent, during NREM sleep (+5 br/min). Atropine increased (P < 0.05) effluent concentrations of serotonin (5-HT), substance P (SP), and glycine during the day and at night. When atropine was dialyzed in one preBötC and mCSF in the contralateral preBötC, 5-HT and SP increased only at the site of atropine dialysis. We conclude: 1) attenuation of a single neuromodulator results in local changes in other neuromodulators that affect ventilatory control, 2) effects of perturbations of cholinergic neuromodulation on breathing are state-dependent, and 3) interpretation of perturbations in vivo requires consideration of direct and indirect effects.
Author List
Muere C, Neumueller S, Miller J, Olesiak S, Hodges MR, Pan L, Forster HVAuthors
Hubert V. Forster PhD Professor in the Physiology department at Medical College of WisconsinMatthew R. Hodges PhD Professor in the Physiology department at Medical College of Wisconsin
MESH terms used to index this publication - Major topics in bold
AcetylcholineAnimals
Atropine
Basal Metabolism
Body Temperature
Cerebrospinal Fluid
Female
Glycine
Goats
Medulla Oblongata
Microdialysis
Neurons
Neurotransmitter Agents
Respiration
Respiratory Mechanics
Serotonin
Sleep Stages
Substance P
Wakefulness
