GABA-mediated inhibition of raphe pallidus neurons regulates sympathetic outflow to brown adipose tissue

Sympathetic nerve activity to brown adipose tissue (BAT) regulates adipocyte metabolism of its stored lipid fuel and thus the thermogenesis in BAT. To determine if the discharge of neurons in the rostral raphe pallidus (RPa) can influence BAT thermogenesis, changes in sympathetic nerve activity to BAT were recorded after microinjection (60 nl) of the GABA(A) receptor antagonist bicuculline (500 μM) into the RPa in chloralose-urethan- anesthetized, ventilated rats. Bicuculline caused a large, rapid rise in the sympathetic nerve activity to BAT (which had also increased during acute hypothermia) from very low, normothermic control levels to maximum values (mean: 1,949 ± 604% control; n = 13) after 4-6 min. The sympathetic nerve discharge to BAT had a mean burst frequency (3.5 ± 0.3 Hz) that was significantly less than the heart rate (7.3 ± 0.2 beats/min), and it was not inhibited during baroreceptor reflex activation. Bicuculline-stimulated increases in the sympathetic nerve activity to BAT and cold-evoked increases in neuronal fos expression were localized to the RPa at the level of the caudal half of the facial nucleus. This dramatic increase in sympathetic nerve activity to BAT after disinhibition of neurons in rostral RPa is consistent with a major role for RPa neurons, perhaps as sympathetic premotoneurons for BAT, in medullary control of BAT thermogenesis.