The lateral habenula (LHb) is an evolutionarily ancient nucleus that plays an important role in the detection of salient/adverse environmental events. We have previously shown that the LHb is involved in brown adipose tissue (BAT) thermogenesis elicited by stressful situations, and that the medullary raphé, a key lower brainstem sympathetic control centre, mediates BAT thermogenesis elicited by stimulating the LHb. Since there are no direct projections from the LHb to the medullary raphé, it is plausible that the dorsomedial hypothalamus (DMH), a brain region known to be important for thermoregulatory responses to stress, is involved in this thermogenic pathway. In this study we aimed to test this possibility. In anaesthetized Sprague-Dawley rats, we recorded electrical discharges directly from sympathetic fibres that innervate BAT, as well as BAT temperature. Injections of bicuculline (1 nmol in 100 nl), a neuronal activator by disinhibition, into the LHb increased BAT sympathetic nerve discharge by 4.9 ± 1.4dBμV (n = 7, P < 0.05) and BAT temperature by 1.0 ± 0.1 °C (n = 7, P < 0.01). Subsequent injections of muscimol (0.25 nmol in 100 nl), a neuronal inhibitor, into the DMH promptly reduced BAT sympathetic nerve discharge by 4.7 ± 1.3 dBμV (n = 7, P < 0.05) and BAT temperature by 0.3 ± 0.1 °C (n = 7, P < 0.05). Injections of a mixture of the ionotropic glutamate receptor antagonists, DL-2-Amino-5-phosphonopentanoic acid (AP5) and 6-cyano-7-nitroquinoxaline-2,3-dioneis (CNQX) into the DMH, after activation of the LHb, also significantly decreased BAT sympathetic nerve discharge and BAT temperature. These results suggest that, for sympathetically-mediated BAT thermogenesis, the DMH is part of the neural circuitry linking the LHb with the medullary raphé.

中文翻译：

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下丘脑背内侧的抑制显着减少了由外侧缰核激活引起的棕色脂肪组织交感神经放电

外侧缰核 (LHb) 是一种进化上古老的细胞核，在检测显着/不利环境事件中起着重要作用。我们之前已经表明 LHb 参与由压力情况引起的棕色脂肪组织 (BAT) 产热，并且髓质中缝是一个关键的下脑干交感神经控制中心，介导通过刺激 LHb 引发的 BAT 产热。由于 LHb 没有直接投射到延髓中缝，因此下丘脑背内侧 (DMH)（一个已知对压力的体温调节反应很重要的大脑区域）可能参与了这种产热途径。在这项研究中，我们旨在测试这种可能性。在麻醉的 Sprague-Dawley 大鼠中，我们记录了直接来自支配 BAT 的交感神经纤维的放电，以及 BAT 温度。将荷包牡丹碱（100 nl 中的 1 nmol）（一种通过去抑制作用的神经元激活剂）注射到 LHb 中使 BAT 交感神经放电增加 4.9 ± 1.4dBμV（n = 7，P < 0.05）和 BAT 温度增加 1.0 ± 0.1 °C（n = 7，P < 0.01）。随后将神经元抑制剂 muscimol（100 nl 中的 0.25 nmol）注射到 DMH 中，迅速将 BAT 交感神经放电减少了 4.7 ± 1.3 dBμV（n = 7，P < 0.05）和 BAT 温度减少了 0.3 ± 0.1 °C（n = 7，P < 0.05）。LHb 激活后，将离子型谷氨酸受体拮抗剂 DL-2-Amino-5-phosphonopentanoic 酸 (AP5) 和 6-cyano-7-nitroquinoxaline-2,3-dioneis (CNQX) 的混合物注射到 DMH 中，也显着降低了 BAT 交感神经放电和 BAT 温度。这些结果表明，