Serotonergic receptor binding is altered in the medullary serotonergic nuclei, including the paragigantocellularis lateralis (PGCL), in many infants who die of sudden infant death syndrome (SIDS). The PGCL receives inputs from many sites in the caudal brainstem and projects to the spinal cord and to more rostral areas important for arousal and vigilance. We have shown previously that local unilateral nonspecific neuronal inhibition in this region with GABA A agonists disrupts sleep architecture. We hypothesized that specifically inhibiting serotonergic activity in the PGCL would result in less sleep and heightened vigilance. We analyzed sleep before and after unilaterally dialyzing the 5-HT 1A agonist (
Activation of 5-HT 1A receptors in the medullary raphé decreases sympathetically mediated brown adipose tissue (BAT) thermogenesis and peripheral vasoconstriction when previously activated with leptin, LPS, prostaglandins, or cooling. It is not known whether shivering is also modulated by medullary raphé 5-HT 1A receptors. We previously showed in conscious piglets that activation of 5-HT 1A receptors with (Ϯ)-8-hydroxy-2-(dipropylamino)-tetralin (8-OH-DPAT) in the paragigantocellularis lateralis (PGCL), a medullary region lateral to the raphé that contains substantial numbers of 5-HT neurons, eliminates rapid eye movement (REM) sleep and decreases shivering in a cold environment, but does not attenuate peripheral vasoconstriction. Hoffman JM, Brown JW, Sirlin EA, Benoit AM, Gill WH, Harris MB, Darnall RA. Am J Physiol Regul Integr Comp Physiol 293: R518 -R527, 2007. We hypothesized that, during cooling, activation of 5-HT 1A receptors in the medullary raphé would also eliminate REM sleep and, in contrast to activation of 5-HT 1A receptors in the PGCL, would attenuate both shivering and peripheral vasoconstriction. In a continuously cool environment, dialysis of 8-OH-DPAT into the medullary raphé resulted in alternating brief periods of non-REM sleep and wakefulness and eliminated REM sleep, as observed when 8-OH-DPAT is dialyzed into the PGCL. Moreover, both shivering and peripheral vasoconstriction were significantly attenuated after 8-OH-DPAT dialysis into the medullary raphé. The effects of 8-OH-DPAT were prevented after dialysis of the selective 5-HT 1A receptor antagonist WAY-100635. We conclude that, during cooling, exogenous activation of 5-HT 1A receptors in the medullary raphé decreases both shivering and peripheral vasoconstriction. Our data are consistent with the hypothesis that neurons expressing 5-HT 1A receptors in the medullary raphé facilitate spinal motor circuits involved in shivering, as well as sympathetic stimulation of other thermoregulatory effector mechanisms. thermoregulation; serotonin; brain stem; raphé; the sudden infant death syndrome MANY NEURONS IN THE MEDULLARY raphé, including serotonergic (5-HT) neurons, project to the intermediolateral cell column (IML) of the spinal cord and modulate sympathetic outflow to thermoregulatory effector mechanisms, including brown adipose tissue (BAT) thermogenesis, vasoconstriction of thermoregulatory cutaneous vascular beds, and heart rate (HR) (14,53,58,86,89). Studies in anesthetized and conscious animals have shown that activation of 5-HT 1A receptors in the medullary raphé with the selective agonist, (Ϯ)-8-hydroxy-2-(dipropylamino)-tetralin (8-OH-DPAT), attenuates sympathetic outflow to BAT and peripheral vessels when previously elevated by LPS, leptin, or cooling (11,52,59,63,64).There is mounting evidence that medullary raphé 5-HT neurons modulate sympathetically mediated thermoregulatory mechanisms; however, little is known about the role of medullary raphé 5-HT neurons in shivering thermogenesis. Shivering is an involuntary tremor that i...
The first decade of the twenty first century has witnessed a tremendous increase in the demand of sustainable buildings mainly due to mounting energy costs and growing environmental concerns. The most effective decisions related to the sustainable design of a building can be made in the planning and design phases. Since Building Information Modeling (BIM) allows for multi-disciplinary information to be superimposed within one model, it creates an opportunity for sustainability measures to be incorporated early in the design process. This paper presents findings of a research project to investigate the feasibility of BIM for sustainability analyses via a case study. Based on the collected data, it is found that BIM can significantly aid in performing complex building performance analyses to ensure an optimized building design. The designers can also use these results to generate necessary documentation for LEED ® certification (a green building rating system used in the USA), thereby saving considerable time and resources.
Activation of 5-HT(1A) receptors in the medullary raphé decreases sympathetic outflow to thermoregulatory mechanisms, including brown adipose tissue (BAT), thermogenesis, and peripheral vasoconstriction when these mechanisms are previously activated with leptin, prostaglandins, or cooling. These same mechanisms are also inhibited during rapid eye movement (REM) sleep. It is not known whether shivering is also modulated by medullary raphé neurons. We previously showed in the conscious piglet that activation of 5-HT(1A) receptors with 8-OH-DPAT (DPAT) in the paragigantocellularis lateralis (PGCL), a medullary region lateral to the midline raphé that contains 5-HT neurons, decreases heart rate, body temperature and muscle activity during non-rapid eye movement (NREM) sleep. We therefore hypothesized that activation of 5-HT(1A) receptors in the PGCL would also attenuate shivering and peripheral vasoconstriction during cooling. During REM sleep in a cool environment, shivering, carbon dioxide production, and body temperature decreased, and ear capillary blood flow and ear skin temperature increased. Shivering associated with rapid cooling was attenuated after dialysis of DPAT into the PGCL. In animals maintained in a continuously cool environment, dialysis of DPAT into the PGCL attenuated shivering and decreased body temperature, but there were no significant increases in ear capillary blood flow or ear skin temperature. We conclude that both naturally occurring REM sleep and exogenous activation of 5-HT(1A) receptors in the PGCL are associated with a suspension of shivering during cooling. Our data are consistent with the hypothesis that 5-HT neurons in the PGCL facilitate oscillating spinal motor circuits involved in shivering but are less involved in modulating sympathetically mediated thermoregulatory mechanisms.
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