Department of Physiology, School of Medicine, Tulane University , New Orleans, Louisiana.
Neuroscience Program, Brain Institute, Tulane University , New Orleans, Louisiana.
J Neurophysiol. 2019 Jan 1;121(1):140-151. doi: 10.1152/jn.00004.2018. Epub 2018 Nov 21.
Transient receptor potential vanilloid type 1 (TRPV1) is a ligand-gated ion channel expressed in the peripheral and central nervous systems. TRPV1-dependent mechanisms take part in a wide range of physiological and pathophysiological pathways including the regulation of homeostatic functions. TRPV1 expression in the hypothalamus has been described as well as evidence that TRPV1-dependent excitatory inputs to hypothalamic preautonomic neurons are diminished in diabetic conditions. Here we aimed to determine the functional expression of TRPV1 in two hypothalamic nuclei known to be involved in the central control of metabolism and to test the hypothesis that TRPV1-expressing neurons receive TRPV1-expressing inputs. A mouse model (TRPV1) was generated to identify TRPV1-expressing cells and determine the cellular properties of TRPV1-expressing neurons in adult mice. Our study demonstrated the functional expression of TRPV1 in the dorsomedial hypothalamic nucleus and paraventricular nucleus in adult mice. Our findings revealed that a subset of TRPV1 neurons receive TRPV1-expressing excitatory inputs, indicating direct interaction between TRPV1-expressing neurons. In addition, astrocytes likely play a role in the modulation of TRPV1-expressing neurons. In summary, this study identified specific hypothalamic regions where TRPV1 is expressed and functional in adult mice and the existence of direct connections between TRPV1 neurons. NEW & NOTEWORTHY Transient receptor potential vanilloid type 1 (TRPV1) is expressed in the hypothalamus, and TRPV1-dependent regulation of preautonomic neurons is decreased in hyperglycemic conditions. Our study demonstrated functional expression of TRPV1 in two hypothalamic nuclei involved in the control of energy homeostasis. Our results also revealed that a subset of TRPV1-expressing neurons receive TRPV1-expressing excitatory inputs. These findings suggest direct interaction between TRPV1-expressing neurons.
瞬时受体电位香草酸型 1(TRPV1)是一种配体门控离子通道,在周围和中枢神经系统中表达。TRPV1 依赖性机制参与了广泛的生理和病理生理途径,包括对体内平衡功能的调节。已经描述了下丘脑的 TRPV1 表达,并且有证据表明,在糖尿病条件下,TRPV1 依赖性兴奋性传入到下丘脑前自主神经元减少。在这里,我们旨在确定两种已知参与代谢的中枢控制的下丘脑核中 TRPV1 的功能表达,并检验 TRPV1 表达神经元接收 TRPV1 表达输入的假设。生成了 TRPV1 小鼠模型(TRPV1)以鉴定 TRPV1 表达细胞并确定成年小鼠中 TRPV1 表达神经元的细胞特性。我们的研究表明 TRPV1 在成年小鼠的下丘脑背内侧核和室旁核中具有功能表达。我们的发现表明,一部分 TRPV1 神经元接收 TRPV1 表达的兴奋性输入,表明 TRPV1 表达神经元之间存在直接相互作用。此外,星形胶质细胞可能在调节 TRPV1 表达神经元中起作用。总之,这项研究确定了 TRPV1 在成年小鼠中表达和功能的特定下丘脑区域,以及 TRPV1 神经元之间存在直接连接。新的和值得注意的 TRPV1 在下丘脑表达,并在高血糖条件下调节自主前神经元的功能降低。我们的研究表明 TRPV1 在两个参与能量稳态控制的下丘脑核中具有功能表达。我们的结果还表明,一部分 TRPV1 表达神经元接收 TRPV1 表达的兴奋性输入。这些发现表明 TRPV1 表达神经元之间存在直接相互作用。