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. 2007 Jan;292(1):R127-36.
doi: 10.1152/ajpregu.00427.2006. Epub 2006 Aug 24.

Central efferent pathways mediating skin cooling-evoked sympathetic thermogenesis in brown adipose tissue

Kazuhiro Nakamura  1 , Shaun F Morrison
Affiliations

Central efferent pathways mediating skin cooling-evoked sympathetic thermogenesis in brown adipose tissue

Kazuhiro Nakamura et al. Am J Physiol Regul Integr Comp Physiol. 2007 Jan.

Abstract

Control of thermoregulatory effectors by the autonomic nervous system is a critical component of rapid cold-defense responses, which are triggered by thermal information from the skin. However, the central autonomic mechanism driving thermoregulatory effector responses to skin thermal signals remains to be determined. Here, we examined the involvement of several autonomic brain regions in sympathetic thermogenic responses in brown adipose tissue (BAT) to skin cooling in urethane-chloralose-anesthetized rats by monitoring thermogenic [BAT sympathetic nerve activity (SNA) and BAT temperature], metabolic (expired CO(2)), and cardiovascular (arterial pressure and heart rate) parameters. Acute skin cooling, which did not reduce either rectal (core) or brain temperature, evoked increases in BAT SNA, BAT temperature, expired CO(2), and heart rate. Skin cooling-evoked thermogenic, metabolic, and heart rate responses were inhibited by bilateral microinjections of bicuculline (GABA(A) receptor antagonist) into the preoptic area (POA), by bilateral microinjections of muscimol (GABA(A) receptor agonist) into the dorsomedial hypothalamic nucleus (DMH), or by microinjection of muscimol, glycine, 8-OH-DPAT (5-HT(1A) receptor agonist), or kynurenate (nonselective antagonist for ionotropic excitatory amino acid receptors) into the rostral raphe pallidus nucleus (rRPa) but not by bilateral muscimol injections into the lateral/dorsolateral part or ventrolateral part of the caudal periaqueductal gray. These results implicate the POA, DMH, and rRPa in the central efferent pathways for thermogenic, metabolic, and cardiac responses to skin cooling, and suggest that these pathways can be modulated by serotonergic inputs to the medullary raphe.

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Figures

Fig. 1
Fig. 1
Changes in BAT SNA, TBAT, expired (Exp.) CO2, HR, arterial pressure (AP), Trec, and Tbrain in response to cooling the trunk skin. The horizontal scale bar represents 100 sec, and the vertical scale bar for the BAT SNA trace represents 100 μV. Note that Trec and Tbrain do not change substantially during the skin cooling and rewarming, indicating that the observed changes in BAT SNA, TBAT, Exp. CO2, HR, and AP were evoked by the effect of skin temperature changes rather than changes in body core parts or in the brain.
Fig. 2
Fig. 2
A and B: Effects of microinjections of saline (A) or bicuculline (B) into the POA on skin cooling-evoked changes in physiological variables. Microinjections were made bilaterally at the time points indicated by arrowheads and broken lines. The horizontal scale bar represents 100 sec, and vertical scale bars for BAT SNA traces represent 50 μV in (A) and 400 μV in (B). C: Location of the sites of all intra-POA microinjections for the group data shown in Table 2. Microinjection sites are plotted on a brain map adopted from an atlas (40). D: Representative view of sites of bilateral microinjections into the POA. Each injection site is clearly identified as a cluster of fluorescent beads (arrows). The scale bar represents 0.5 mm. Abbreviations: 3V, third ventricle; ac, anterior commissure; ADP, anterodorsal preoptic nucleus; LPO, lateral preoptic area; MnPO, median preoptic nucleus; MPO, medial preoptic area; ox, optic chiasm; and PS, parastrial nucleus.
Fig. 3
Fig. 3
A and B: Effects of microinjections of saline (A) or muscimol (B) into the dorsomedial hypothalamic region consisting of the DMH and DH on skin cooling-evoked changes in physiological variables. Microinjections were made bilaterally at the time points indicated by arrowheads and broken lines. The horizontal scale bar represents 100 sec, and vertical scale bars for BAT SNA traces represent 300 μV in (A) and 50 μV in (B). C: Location of the sites of all intra-DMH/DH microinjections for the group data shown in Table 2. D: Representative view of sites of bilateral microinjections into the DMH as indicated by clusters of fluorescent beads (arrows). The scale bar represents 0.5 mm. Abbreviations: f, fornix; mt, mammillothalamic tract; and VMH, ventromedial hypothalamic nucleus.
Fig. 4
Fig. 4
A–E: Effects of microinjections of saline (A), muscimol (B), glycine (C), kynurenate (D), or 8-OH-DPAT (E) into the rRPa on skin cooling-evoked changes in physiological variables. Microinjection was made at the time point indicated by an arrowhead and broken line. The horizontal scale bar represents 100 sec, and vertical scale bars for BAT SNA traces represent 100 μV in (A and C), 50 μV in (B), 400 μV in (D), and 40 μV in (E). F: Location of the sites of all microinjections into and around the rRPa for the group data shown in Table 2. G: Representative view of a microinjection site into the rRPa as indicated by a cluster of fluorescent beads (arrow). The scale bar represents 0.5 mm. Abbreviations: Giα, alpha part of the gigantocellular reticular nucleus; py, pyramidal tract; RMg, raphe magnus nucleus; and ROb, raphe obscurus nucleus.
Fig. 5
Fig. 5
A and D: Effects of muscimol microinjections into the l/dlcPAG (A) or vlcPAG (D) on skin cooling-evoked changes in physiological variables. Microinjections were made bilaterally at the time points indicated by arrowheads and broken lines. The horizontal scale bar represents 100 sec, and vertical scale bars for BAT SNA traces represent 150 μV in (A) and 15 μV in (D). B and E: Location of the sites of all microinjections into the l/dlcPAG (B) and vlcPAG (E) for the group data shown in Table 2. C and F: Representative views of sites of bilateral microinjections into the l/dlcPAG (C) and vlcPAG (F) as indicated by clusters of fluorescent beads (arrows). The scale bar represents 0.5 mm. Abbreviations: Aq, aqueduct; dmcPAG, dorsomedial caudal periaqueductal gray; DR, dorsal raphe nucleus; IC, inferior colliculus; mlf, medial longitudinal fasciculus; SC, superior colliculus; and scp, superior cerebellar peduncle.
Fig. 6
Fig. 6
A current model of the neural pathways mediating skin cooling-evoked BAT thermogenesis. In a normothermic environment (Normothermic), GABAergic neurons in the POA tonically inhibit neurons in the DMH. In a cold environment (Cold), signals from somatosensory nerves in the skin activate GABAergic neurons in unknown regions through afferent pathways. The activated GABAergic neurons in the afferent pathway suppress the tonic firing of the GABAergic neurons in the POA and, thereby, disinhibited DMH neurons which activate BAT-controlling sympathetic premotor neurons in the rRPa, leading, in turn, to stimulation of the BAT-controlling sympathetic output system. For detailed discussion, see text. Blue, red, and black circles denote cell bodies of activated inhibitory neurons, activated excitatory neurons, and suppressed or resting neurons, respectively. Abbreviations: DH, dorsal horn; DRG, dorsal root ganglion; and IML, intermediolateral cell column.
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Comment in

  • The cold path to BAT.
    McAllen RM. McAllen RM. Am J Physiol Regul Integr Comp Physiol. 2007 Jan;292(1):R124-6. doi: 10.1152/ajpregu.00651.2006. Epub 2006 Sep 21. Am J Physiol Regul Integr Comp Physiol. 2007. PMID: 16990485 No abstract available.

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