Recording and neural circuit-based manipulation of the maternal oxytocin pulses in mice
Recording and neural circuit-based manipulation of the maternal oxytocin pulses in mice
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小鼠母体催产素脉冲的记录和基于神经回路的操作
DOI：
10.1101/2021.07.26.453888
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发表时间：
2021
期刊：
影响因子：
--
通讯作者：
Miyamichi Kazunari
中科院分区：
文献类型：
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作者：
Yukinaga Hiroko;Hagihara Mitsue;Tsujimoto Kazuko;Chiang Hsiao-Ling;Kato Shigeki;Kobayashi Kazuto;Miyamichi Kazunari
催产素（OT）的脉冲式释放介导分娩期间的子宫收缩和哺乳期间的乳汁排出。1 - 3这些脉冲由位于室旁和视上下丘脑的中枢神经内分泌OT神经元的独特活动模式产生。经典研究通过大鼠和家兔体内细胞外记录技术表征了推定的OT神经元。1，4 - 10然而，由于技术限制，这些先前研究中的OT神经元的身份是基于其电生理特征和轴突投射到垂体后叶的推测，而不是OT基因表达。为了确定投射到垂体的其他下丘脑神经元中的OT神经活动11，12并更好地利用细胞类型特异性神经科学工具包，13需要开发用于分娩和哺乳研究的小鼠模型。我们在此介绍了病毒遗传学的方法在小鼠中的特点OT神经元的母源性活动的纤维光度法。一个尖锐的光度峰值OT神经元出现在约520秒后，同时吸吮刺激从三个幼崽。峰值的幅度随着母鼠哺乳而增加，与幼仔的年龄无关，这表明母体OT神经元的内在可塑性。基于对OT神经元的单突触输入映射，我们通过药物遗传学激活终纹床核中的抑制性神经元，发现OT神经元的活动受到抑制。总的来说，我们的研究阐明了OT神经元的母体神经活动的时间动态，并确定了它的调制输入之一。
Pulsatile release of the hormone oxytocin (OT) mediates uterine contraction during parturition and milk ejection during lactation.1–3These pulses are generated by the unique activity patterns of the central neuroendocrine OT neurons located in the paraventricular and supraoptic hypothalamus. Classical studies have characterized putative OT neurons byin vivoextracellular recording techniques in rats and rabbits.1,4–10Due to technical limitations, however, the identity of OT neurons in these previous studies was speculative based on their electrophysiological characteristics and axonal projection to the posterior pituitary, not onOTgene expression. To pinpoint OT neural activities among other hypothalamic neurons that project to the pituitary11,12and make better use of cell-type-specific neuroscience toolkits,13a mouse model needs to be developed for the studies of parturition and lactation. We herein introduce viral genetic approaches in mice to characterize the maternal activities of OT neurons by fiber photometry. A sharp photometric peak of OT neurons appeared at approximately 520 s following simultaneous suckling stimuli from three pups. The amplitude of the peaks increased as the mother mice experienced lactation, irrespective of the age of the pups, suggesting the intrinsic plasticity of maternal OT neurons. Based on a mono-synaptic input map to OT neurons, we pharmacogenetically activated the inhibitory neurons in the bed nucleus of the stria terminalis and found the suppression of the activities of OT neurons. Collectively, our study illuminates temporal dynamics in the maternal neural activities of OT neurons and identifies one of its modulatory inputs.