Linehan Victoria, Hirasawa Michiru
Division of Biomedical Sciences, Faculty of Medicine, Memorial University, St. John's, NL, Canada.
Front Cell Neurosci. 2018 Mar 13;12:70. doi: 10.3389/fncel.2018.00070. eCollection 2018.
Orexin and melanin-concentrating hormone (MCH) neurons have complementary roles in various physiological functions including energy balance and the sleep/wake cycle. electrophysiological studies investigating these cells typically use post-weaning rodents, corresponding to adolescence. However, it is unclear whether these neurons are functionally mature at this period and whether these studies can be generalized to adult cells. Therefore, we examined the electrophysiological properties of orexin and MCH neurons in brain slices from post-weaning rats and found that MCH neurons undergo an age-dependent reduction in excitability, but not orexin neurons. Specifically, MCH neurons displayed an age-dependent hyperpolarization of the resting membrane potential (RMP), depolarizing shift of the threshold, and decrease in excitatory transmission, which reach the adult level by 7 weeks of age. In contrast, basic properties of orexin neurons were stable from 4 weeks to 14 weeks of age. Furthermore, a robust short-term facilitation of excitatory synapses was found in MCH neurons, which showed age-dependent changes during the post-weaning period. On the other hand, a strong short-term depression was observed in orexin neurons, which was similar throughout the same period. These differences in synaptic responses and age dependence likely differentially affect the network activity within the lateral hypothalamus where these cells co-exist. In summary, our study suggests that orexin neurons are electrophysiologically mature before adolescence whereas MCH neurons continue to develop until late adolescence. These changes in MCH neurons may contribute to growth spurts or consolidation of adult sleep patterns associated with adolescence. Furthermore, these results highlight the importance of considering the age of animals in studies involving MCH neurons.
食欲素和黑色素聚集激素（MCH）神经元在包括能量平衡和睡眠/觉醒周期在内的各种生理功能中发挥着互补作用。研究这些细胞的电生理研究通常使用断奶后的啮齿动物，相当于青春期。然而，目前尚不清楚这些神经元在此期间是否功能成熟，以及这些研究是否可以推广到成年细胞。因此，我们检查了断奶后大鼠脑片中食欲素和MCH神经元的电生理特性，发现MCH神经元的兴奋性随年龄增长而降低，而食欲素神经元则不然。具体而言，MCH神经元表现出静息膜电位（RMP）随年龄增长而超极化、阈值去极化偏移以及兴奋性传递降低，这些在7周龄时达到成年水平。相比之下，食欲素神经元的基本特性在4周龄至14周龄期间保持稳定。此外，在MCH神经元中发现了兴奋性突触的强烈短期易化，在断奶后期间表现出年龄依赖性变化。另一方面，在食欲素神经元中观察到强烈的短期抑制，在同一时期内相似。这些突触反应和年龄依赖性的差异可能对这些细胞共存的下丘脑外侧的网络活动产生不同影响。总之，我们的研究表明，食欲素神经元在青春期前电生理成熟，而MCH神经元持续发育直至青春期后期。MCH神经元的这些变化可能有助于与青春期相关的生长突增或成年睡眠模式的巩固。此外，这些结果突出了在涉及MCH神经元的研究中考虑动物年龄的重要性。
