Medullary pathways mediating specific sympathetic responses to activation of dorsomedial hypothalamus.
ABSTRACT We sought to determine which medullary sympathetic premotor neurons mediate the cardiovascular and thermogenic effects resulting from activation of neurons in the dorsomedial hypothalamus (DMH) in urethane/chloralose-anesthetized, artificially ventilated rats. Unilateral disinhibition of neurons in the DMH with microinjection of bicuculline (2 mM, 30 nl) caused significant increases in brown adipose tissue sympathetic nerve activity (BAT SNA, +828+/-169% of control, n=16), cardiac SNA (+516+/-82% of control, n=16), renal SNA (RSNA, +203+/-25% of control, n=28) and, accompanied by increases in BAT temperature (+1.6+/-0.3 degrees C, n=11), end-tidal CO(2) (+0.7+/-0.1%, n=15), heart rate (+113+/-7 beats/min, n=32), arterial pressure (+19+/-2 mm Hg, n=32) and plasma epinephrine and norepinephrine concentrations. Inhibition of neurons in the rostral raphe pallidus (RPa) with microinjection of muscimol (6 mM, 60 nl) abolished the increases in BAT SNA and BAT temperature and reduced the tachycardia induced by disinhibition of DMH neurons. Inhibition of neurons in the RVLM with microinjection of muscimol (6 mM, 60 nl) markedly reduced the increase in RSNA, but did not affect the evoked tachycardia or the increase in arterial pressure. Combined glutamic acid decarboxylase (GAD-67) immunocytochemistry and pseudorabies viral retrograde tracing from BAT indicated close appositions between GABAergic terminals and DMH neurons in sympathetic pathways to BAT. In conclusion, these results demonstrate the existence of a tonically active, GABAergic inhibitory input to neurons in the DMH and that blockade of this inhibition increases sympathetic outflow to thermogenic and cardiovascular targets by activating functionally specific populations of sympathetic premotor neurons: the excitation of BAT SNA and BAT thermogenesis is mediated through putative sympathetic premotor neurons in the RPa, while the activation in RSNA is dependent on those in RVLM. These data increase our understanding of the central pathways mediating changes in sympathetically mediated thermogenesis that is activated in thermoregulation, stress responses and energy balance.
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ABSTRACT: The tail and paws in rodents are heat exchangers involved in the maintenance of core body temperature. They are also the most widely used target organs to study acute or chronic "models" of pain. We describe the fluctuations of vasomotor tone in the tail and paws in conditions of thermal neutrality and the constraints of these physiological processes on the responses to thermal nociceptive stimuli commonly used as an index of pain. Skin temperatures were recorded with a calibrated thermal camera to monitor changes of vasomotor tone in the tail and paws of awake and anaesthetized rats. In thermo-neutral conditions, the sympathetic tone fluctuated at a rate of 2-7 cycles/hour. Increased arterial blood pressure (~ 46 mmHg) was followed by increased heart rate (~ 45 bpm) in half a minute, vasoconstriction of extremities (3.5-7°C range) within 3-5 minutes, and increased core temperature (~ 0.7°C) within 6 minutes. Decreased arterial blood pressure was followed by opposite events. There was a high correlation between heart rate and core body temperature recorded 5-6 minutes later. The reaction time of the animal's response to a radiant thermal stimulus - heat ramp (6°C/s, 20 mm(2) spot) generated by a CO2 laser - directed to the tail, was strongly dependent of these variations. Consequently, the fluctuations in tail and paw temperature thus represent a serious confound for nociceptive tests, particularly when they are conducted at thermal neutrality.Journal of Neurophysiology 07/2014; · 3.04 Impact Factor
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ABSTRACT: behavioral model of acute pain paws in thermoneutral conditions and its impact on a Thermoregulatory vasomotor tone of the rat tail and You might find this additional info useful... for this article can be found at: Supplemental material /content/suppl/2014/07/17/jn.00721.2013.DC1.html 83 articles, 33 of which can be accessed free at: This article cites /content/112/9/2185.full.html#ref-list-1 1 other HighWire hosted articles This article has been cited by [PDF] [Full Text] [Abstract] , November 1, 2014; 112 (9): 2199-2217. J Neurophysiol Nabil El Bitar, Bernard Pollin and Daniel Le Bars conditions: are they involved in thermoregulation? ''On-'' and ''off-'' cells in the rostral ventromedial medulla of rats held in thermoneutral including high resolution figures, can be found at: Updated information and services /content/112/9/2185.full.html can be found at: Journal of Neurophysiology about Additional material and information http://www.the-aps.org/publications/jn This information is current as of November 4, 2014.J Neurophyiol. 11/2014; 112(4):2185-2198.
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ABSTRACT: The dorsomedial hypothalamus (DMH) and lateral/dorsolateral periaqueductal gray (PAG) are anatomically and functionally connected. Both the DMH and PAG depend on glutamatergic inputs for activation. We recently reported that removal of GABA-ergic tone in the unilateral DMH produces: asymmetry, that is, a right- (R-) sided predominance in cardiac chronotropism, and lateralization, that is, a greater increase in ipsilateral renal sympathetic activity (RSNA). In the current study, we investigated whether excitatory amino acid (EAA) receptors in the DMH-PAG pathway contribute to the functional interhemispheric difference. In urethane (1.2 to 1.4 g/kg, i.p.) anesthetized rats, we observed that: (i) nanoinjections of N-methyl D-aspartate (NMDA 100 pmol/100 nl) into the unilateral DMH produced the same right-sided predominance in the control of cardiac chronotropy, (ii) nanoinjections of NMDA into the ipsilateral DMH or PAG evoked lateralized RSNA responses, and (iii) blockade of EAA receptors in the unilateral DMH attenuated the cardiovascular responses evoked by injection of NMDA into either the R- or left- (L-) PAG. In awake rats, nanoinjection of kynurenic acid (1 nmol/100 nL) into the L-DMH or R- or L-PAG attenuated the tachycardia evoked by air stress. However, the magnitude of stress-evoked tachycardia was smallest when the EAA receptors of the R-DMH were blocked. We conclude that EAA receptors contribute to the right-sided predominance in cardiac chronotropism. This interhemispheric difference that involves EAA receptors was observed in the DMH but not in the PAG.PLoS ONE 11/2014; 9(11):e112412. · 3.53 Impact Factor