Scintillon Institute, San Diego, CA, USA.
Endocrinology. 2021 Feb 1;162(2). doi: 10.1210/endocr/bqaa217.
Arginine vasopressin (AVP) is a neuropeptide acting as a neuromodulator in the brain and plays multiple roles, including a thermoregulatory one. However, the cellular mechanisms of action are not fully understood. Carried out are patch clamp recordings and calcium imaging combined with pharmacological tools and single-cell RT-PCR to dissect the signaling mechanisms activated by AVP. Optogenetics combined with patch-clamp recordings were used to determine the neurochemical nature of these neurons. Also used is telemetry combined with chemogenetics to study the effect of activation of AVP neurons in thermoregulatory mechanisms. This article reports that AVP neurons in the medial preoptic (MPO) area release GABA and display thermosensitive firing activity. Their optogenetic stimulation results in a decrease of the firing rates of MPO pituitary adenylate cyclase-activating polypeptide (PACAP) neurons. Local application of AVP potently modulates the synaptic inputs of PACAP neurons, by activating neuronal AVPr1a receptors and astrocytic AVPr1b receptors. Chemogenetic activation of MPO AVP neurons induces hyperthermia. Chemogenetic activation of all AVP neurons in the brain similarly induces hyperthermia and, in addition, decreases the endotoxin activated fever as well as the stress-induced hyperthermia.
精氨酸加压素（AVP）是一种作为脑内神经调质的神经肽，发挥多种作用，包括体温调节作用。然而，其作用的细胞机制尚不完全清楚。通过膜片钳记录和钙成像，结合药理学工具和单细胞 RT-PCR，我们对 AVP 激活的信号转导机制进行了剖析。利用光遗传学结合膜片钳记录，确定了这些神经元的神经化学性质。还使用遥测技术结合化学遗传学来研究激活 AVP 神经元对体温调节机制的影响。本文报道，视前内侧核（MPO）区的 AVP 神经元释放 GABA，并表现出热敏性放电活动。它们的光遗传学刺激导致 MPO 促肾上腺皮质素释放肽（PACAP）神经元的放电率下降。AVP 通过激活神经元 AVPr1a 受体和星形胶质细胞 AVPr1b 受体，强烈调制 PACAP 神经元的突触输入。MPO AVP 神经元的化学遗传激活诱导体温升高。脑内所有 AVP 神经元的化学遗传激活同样诱导体温升高，并降低内毒素激活的发热以及应激诱导的发热。
