Impacts of sex differences on optogenetic, chemogenetic, and calcium-imaging tools

Impacts of sex differences on optogenetic, chemogenetic, and calcium-imaging tools
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DOI:
10.1016/j.conb.2023.102817
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发表时间:
2023-12-01
影响因子:
5.7
通讯作者:
Trainor,Brian C.
Trainor,Brian C.
中科院分区:
医学2区
文献类型:
--
作者:
Salazar,Valentina I. Cea;Perez,Melvin D.;Trainor,Brian C.

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神经科学的技术创新引入了强大的工具,通过光学、化学发生和钙成像工具来测量和操纵神经元的活动。这些工具最初主要在雄性动物身上进行测试,但现在也越来越多地在雌性动物身上使用。在这篇综述中,我们考虑了这些工具在男性和女性中如何不同地发挥作用。例如,我们回顾了化学生成配体代谢中的性别差异及其下游信号效应。光学工具更直接地改变神经元的去极化或超极化,但生物性和性腺激素调节突触输入和内在兴奋性。我们回顾的研究表明,光遗传操作有时在啮齿动物的发情周期中是一致的,但在某些回路中;操作可能在卵巢周期中有所不同。最后,钙成像方法利用遗传编码的钙指示器来测量神经元的活动。睾酮和雌二醇可以直接调节钙内流,我们认为这些暗示可以解释钙成像研究的结果。总而言之,我们的发现表明,这些神经科学工具有时在男性和女性身上的作用可能不同,使用者在应用这些方法时应该意识到这些差异。
Technical innovation in neuroscience introduced powerful tools for measuring and manipulating neuronal activity via optical, chemogenetic, and calcium-imaging tools. These tools were initially tested primarily in male animals but are now increasingly being used in females as well. In this review, we consider how these tools may work differently in males and females. For example, we review sex differences in the metabolism of chemogenetic ligands and their downstream signaling effects. Optical tools more directly alter depolarization or hyperpolarization of neurons, but biological sex and gonadal hormones modulate synaptic inputs and intrinsic excitability. We review studies demonstrating that optogenetic manipulations are sometimes consistent across the rodent estrous cycle but within certain circuits; manipulations can vary across the ovarian cycle. Finally, calcium-imaging methods utilize genetically encoded calcium indicators to measure neuronal activity. Testosterone and estradiol can directly modulate calcium influx, and we consider these implications for interpreting the results of calcium-imaging studies. Together, our findings suggest that these neuroscientific tools may sometimes work differently in males and females and that users should be aware of these differences when applying these methods.