光遗传学工具在学习记忆中的应用研究

doi:10.12211/2096-8280.2024-042

摘要/Abstract

摘要：

光遗传学是一种结合光学和遗传学的新型细胞生物学工具。通过引入光激活通道（光敏感蛋白基因）到特定的神经元群体，光遗传学能够以毫秒级精度对这些神经元进行非侵入性光学控制。这一技术的进步为研究学习和记忆的神经生物学基础提供了强大支持。通过在活体动物中精确操控神经元活动，研究人员可以更详细地分析神经网络的功能，探索学习和记忆过程中的分子、细胞和神经回路机制。光遗传学不仅揭示了突触可塑性在记忆形成中的关键作用，还通过特定波长的光激活或抑制神经元，实现记忆的生成、消除和恢复。本文综述了光遗传学工具在学习和记忆研究中的应用，包括不同波长光照对受体的影响、光学刺激对记忆的激活和抑制，以及基于光遗传学的神经功能增强研究方法。然而，在光遗传学的应用过程中仍存在一些挑战，例如开发安全且高效的基因传递载体、优化光敏蛋白的性能、探索其在临床环境中转化的可行性等。解决这些问题对于光遗传学的进一步发展至关重要。未来，随着光遗传学工具的持续优化和跨学科技术的融合应用，这项技术有望在治疗神经系统疾病、增强认知功能与成瘾研究等领域提供新的理论基础和实践方法。

关键词: 光遗传学, 光敏感蛋白质, 记忆, 离子通道, 神经可塑性

Abstract:

Optogenetics represents an advanced technology that facilitates precise control of gene expression and neuronal activity in living cells through light. Introduced by neuroscientist K. Deisseroth in 2005, this methodology has transformed neuroscience research, empowering researchers to modulate excitable tissues and neural circuits with exceptional spatiotemporal accuracy. Optogenetics necessitates the expression of light-sensitive proteins, including channelrhodopsins, halorhodopsins, and various microbial opsins, within specific cells. Employing viral vectors and tissue-specific promoters, these proteins ensure targeted expression. Exposure to designated wavelengths of light permits these proteins to activate or inhibit cellular activity, thereby modulating neuronal behavior. The implementation of optogenetics has significantly enhanced comprehension of learning, memory, and neural plasticity. This technology enables the examination of the molecular dynamics associated with synaptic plasticity, long-term potentiation (LTP), and long-term depression (LTD), which are pivotal for memory. Real-time manipulating of specific neuronal populations can elucidate the intricate neural circuits involved in these phenomena. Additionally, optogenetics has facilitated the exploration of potential therapeutic approaches for neurological conditions such as Alzheimer’s disease by meticulously controlling memory-associated circuits. The utility of optogenetics transcends fundamental research, yielding promising prospects in addiction to studies and motor function enhancement. By modulating distinct neural circuits, it is possible to alter addiction-related behaviors and augment motor functions. Furthermore, the amalgamation of optogenetics with cutting-edge technologies like artificial intelligence and deep learning is anticipated to refine stimulation protocols, resulting in more precise and efficacious experimental outcomes. Notwithstanding its transformative capacity, the clinical application of optogenetics encounters significant obstacles, including the requisites for safe and effective gene delivery systems and the formulation of light-sensitive proteins with optimal characteristics for applications in human beings. Future investigations should concentrate on surmounting these hurdles while expanding the applications of optogenetics in neuroscience and related fields. The integration of optogenetics with multidisciplinary approaches is poised to unveil new realms in brain research, yielding profound insights into mechanisms governing memory, learning, and neural plasticity.

Key words: optogenetics, photosensitive proteins, memory, ion channels, neural plasticity

中图分类号:

郑益坤, 郑婕, 胡国鹏. 光遗传学工具在学习记忆中的应用研究[J]. 合成生物学, 2025, 6(1): 87-104.

Yikun ZHENG, Jie ZHENG, Guopeng HU. Research on the application of optogenetic tools in learning and memory[J]. Synthetic Biology Journal, 2025, 6(1): 87-104.

图/表 5

图1 突触连接强化示意图（图中展示神经元A、R和B之间的突触连接如何通过重复的电生理刺激得到增强。该过程模拟信息的重复编码机制，并反映了形成长期记忆的基本原理。根据Hebb法则，如果两个神经元频繁且近距离地共同活动，相关突触连接将得到加强，从而提高信息传递的效率并增强突触后的反应能力）

Fig.1 Diagram of strengthening synaptic connections(The diagram illustrates how synaptic connections between neurons A, R, and B are strengthened through repeated electrophysiological stimulations. This process simulates the mechanism of repeated encoding of information and reflects the fundamental principles of long-term memory formation. According to Hebb’s rule, if two neurons frequently and closely act together, the associated synaptic connections will be strengthened, thereby improving the efficiency of information transmission, and enhancing the postsynaptic response.)

图2 通过Hebb法则增强特定神经元突触连接（Hebb法则在突触可塑性中的应用表明，反复激活特定神经元可以增强突触连接，这一机制是学习和记忆形成过程中的基础组成部分）

Fig. 2 Specific neuronal synaptic connections enhanced by the Hebb’s rule(Applications of the Hebb’s rule in synaptic plasticity indicate that repeated activation of specific neurons can enhance synaptic connections, a mechanism that is fundamental in the processes of learning and memory formation.)

图3 信号分隔与整合传递处理架构［32］

Fig. 3 Architecture for signal segregation and integration transmission processing [32]

图4 光遗传学工具及其作用机制

Fig. 4 Optogenetic tools and their working mechanisms

图5 人工插入记忆与实际记忆由相同神经环路编码［114］

Fig. 5 Artificially inserted memories and actual memories are encoded by the same neural circuit［114］

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