title: Atropine microdialysis within or near the pre-Botzinger Complex increases breathing frequency more during wakefulness than during NREM sleep.
abstract: 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.
authors.affiliation: Department of Physiology, Medical College of Wisconsin, Milwaukee, Wisconsin 53226, USA.
authors.forename: Clarissa
authors.initials: C
authors.lastname: Muere
authors.forename: Suzanne
authors.initials: S
authors.lastname: Neumueller
authors.forename: Justin
authors.initials: J
authors.lastname: Miller
authors.forename: Samantha
authors.initials: S
authors.lastname: Olesiak
authors.forename: Matthew R
authors.initials: MR
authors.lastname: Hodges
authors.forename: Lawrence
authors.initials: L
authors.lastname: Pan
authors.forename: Hubert V
authors.initials: HV
authors.lastname: Forster
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001285:Atropine / Q000494:pharmacology*; D001481:Basal Metabolism / Q000187:drug effects / Q000502:physiology; D001831:Body Temperature / Q000187:drug effects / Q000502:physiology; D002555:Cerebrospinal Fluid / Q000187:drug effects / Q000378:metabolism; D005260:Female; D005998:Glycine / Q000378:metabolism; D006041:Goats; D008526:Medulla Oblongata / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D017551:Microdialysis / Q000379:methods; D009474:Neurons / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D018377:Neurotransmitter Agents / Q000494:pharmacology; D012119:Respiration / Q000187:drug effects*; D015656:Respiratory Mechanics / Q000187:drug effects / Q000502:physiology; D012701:Serotonin / Q000378:metabolism; D012894:Sleep Stages / Q000187:drug effects* / Q000502:physiology; D013373:Substance P / Q000378:metabolism; D014851:Wakefulness / Q000187:drug effects* / Q000502:physiology
chemical_list: D018377:Neurotransmitter Agents; D012701:Serotonin; D013373:Substance P; D001285:Atropine; D000109:Acetylcholine; D005998:Glycine