title: Glycinergic inhibition of BAT sympathetic premotor neurons in rostral raphe pallidus.
abstract: The rostral raphe pallidus (rRPa) contains sympathetic premotor neurons controlling thermogenesis in brown adipose tissue (BAT). We sought to determine whether a tonic activation of glycineAreceptors (GlyAR) in the rRPa contributes to the inhibitory regulation of BAT sympathetic nerve activity (SNA) and of cardiovascular parameters in anesthetized rats. Nanoinjection of the GlyAR antagonist, strychnine (STR), into the rRPa of intact rats increased BAT SNA (peak: +495%), BAT temperature (TBAT, +1.1°C), expired CO2, (+0.4%), core body temperature (TCORE, +0.2°C), mean arterial pressure (MAP, +4 mmHg), and heart rate (HR, +57 beats/min). STR into rRPa in rats with a postdorsomedial hypothalamus transection produced similar increases in BAT thermogenic and cardiovascular parameters. Glycine nanoinjection into the rRPa evoked a potent inhibition of the cooling-evoked increases in BAT SNA (nadir: -74%), TBAT(-0.2°C), TCORE(-0.2°C), expired CO2(-0.2%), MAP (-8 mmHg), and HR (-22 beats/min) but had no effect on the increases in these variables evoked by STR nanoinjection into rRPa. Nanoinjection of GABA into the rRPa inhibited the STR-evoked BAT SNA (nadir: -86%) and reduced the expired CO2(-0.4%). Blockade of glutamate receptors in rRPa reduced the STR-evoked increases in BAT SNA (nadir: -61%), TBAT(-0.5°C), expired CO2(-0.3%), MAP (-9 mmHg), and HR (-33 beats/min). We conclude that a tonically active glycinergic input to the rRPa contributes to the inhibitory regulation of the discharge of BAT sympathetic premotor neurons and of BAT thermogenesis and energy expenditure.
authors.affiliation: Department of Neurological Surgery, Oregon Health & Science University, Portland, Oregon santosda@ohsu.edu.
authors.forename: Ellen Paula Santos da
authors.initials: EP
authors.lastname: Conceição
authors.affiliation: Department of Neurological Surgery, Oregon Health & Science University, Portland, Oregon.
authors.forename: Christopher J
authors.identifier: 0000-0001-6949-5695
authors.initials: CJ
authors.lastname: Madden
authors.affiliation: Department of Neurological Surgery, Oregon Health & Science University, Portland, Oregon.
authors.forename: Shaun F
authors.initials: SF
authors.lastname: Morrison
mesh_terms: D000200:Action Potentials; D002001:Adipose Tissue, Brown / Q000294:innervation*; D000818:Animals; D062186:Arterial Pressure; D002319:Cardiovascular System / Q000294:innervation*; D005998:Glycine / Q000378:metabolism*; D018684:Glycine Agents / Q000008:administration & dosage; D006339:Heart Rate; D007267:Injections; D008297:Male; D066267:Midbrain Raphe Nuclei / Q000187:drug effects / Q000378:metabolism*; D009046:Motor Neurons / Q000187:drug effects / Q000378:metabolism*; D009433:Neural Inhibition / Q000187:drug effects; D017207:Rats, Sprague-Dawley; D018009:Receptors, Glycine / Q000037:antagonists & inhibitors / Q000378:metabolism*; D013564:Sympathetic Nervous System / Q000187:drug effects / Q000378:metabolism*; D022722:Thermogenesis / Q000187:drug effects; D013997:Time Factors
chemical_list: D018684:Glycine Agents; D018009:Receptors, Glycine; D005998:Glycine
keywords: brown adipose tissue; dorsomedial hypothalamus; glycineA receptor; strychnine; thermoregulation