The Application Progress of Optogenetics in Neuroscience and Behavioral Studies

Research Article
Open access

The Application Progress of Optogenetics in Neuroscience and Behavioral Studies

Qizheng Xu 1*
  • 1 Shanxi University    
  • *corresponding author a18173400781@outlook.com
Published on 6 December 2024 | https://doi.org/10.54254/2753-8818/2024.18022
TNS Vol.66
ISSN (Print): 2753-8826
ISSN (Online): 2753-8818
ISBN (Print): 978-1-83558-763-8
ISBN (Online): 978-1-83558-764-5

Abstract

Optogenetics, as an emerging interdisciplinary technology, has enabled the precise manipulation of neuronal activity by combining optical and genetic approaches. This paper summarizes the application of optogenetics in neuroscience and behavioral research and introduces its research background and topics. The application of optogenetics in neuronal activity regulation, neural loop resolution, exploration of learning and memory mechanisms, and treating neurological diseases were focused on. By combining a literature review and case analysis, we analyze the core principles of optogenetics and the technical points of optogenetics and demonstrate their potential applications in different research scenarios. The types and properties of photosensitive proteins and their application strategies in experiments are detailed, demonstrating the unique advantages of optogenetics in revealing the mysteries of neurobiological processes. The results show that optogenetic technology provides a powerful tool to reveal the mysteries of neurobiological processes, but it still faces challenges such as light transmission efficiency and gene delivery safety in practical applications. This paper summarizes the advantages and limitations of optogenetics and prospects for its future direction, providing an important reference for the continuous development of neuroscience and behavioral research.

Keywords:

Optogenetics, Neuroscience, Behavioral Science, Neuronal Activity Regulation, Neural Circuit Analysis

Xu,Q. (2024). The Application Progress of Optogenetics in Neuroscience and Behavioral Studies. Theoretical and Natural Science,66,108-113.
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1. Introduction

Neuroscience and behavioral science are being driven by technological innovation and are ushering in profound changes. As an emerging interdisciplinary technology, optogenetics realizes the precise control of neuronal activity through the combination of optics and genetics, providing a new tool for neuroscience and behavioral research [1]. This technology uses light-sensitive proteins to convert light signals into intracellular signals, enabling non-invasive, high spatial otemporal resolution neuronal manipulation, broadening our understanding of the complex functions of the nervous system.

Optogenetics has made significant progress in the fields of neuronal activity regulation, neural loop resolution, learning and memory exploration, and neurological disease treatment. For example, it has been successfully used to regulate robotic movement in rats, revealing simple nervous system behavioral mechanisms. However, these problems such as light transmission efficiency, gene transmission safety and long-term expression stability still need to be solved, and the application in complex nervous systems need to be expanded.

This study summarizes the latest progress of optogenetics in neuroscience and behavior, and uses literature review and case analysis methods to analyze its application and advantages in neuronal regulation, loop analysis, learning and memory mechanisms and the treatment of neurological diseases, and discusses the challenges and future directions. A systematic search of high-quality research literature outlines the principles of optogenetics, and technical points to demonstrate its potential in different research scenarios.

This study has not only academic value but also a broad social significance and application prospect. A comprehensive review of the progress in optogenetics will help to promote the development of neuroscience and behavior and provide new ideas and methods for solving neurological diseases. Looking forward, optogenetics will continue to play a key role in the neuroscience field and promote the progress and development of the discipline.

2. An Overview of Optogenetic Technologies

2.1. Definition and principle of optogenetics

Optogenetics, as a leading interdisciplinary discipline, combines the techniques of optics and genetics to study the function of the nervous system through the precise control of biological processes within cells. The core mechanism is the use of specific light-sensitive proteins, which usually originate from microbial rhodopsin (such as proteins in halophiles), to specifically activate or inhibit specific neuronal activity [1] in a living organism in a highly spatially and temporally resolved manner.

One of the key steps towards this goal is the introduction of genes encoding these photosensitive proteins into target cells by genetic engineering techniques. Once successfully expressed, these light-sensitive proteins give the cell sensitivity to a specific wavelength of light [2]. For example, Channelrhodopsin-2 (Chr 2) is a light-sensitive protein found in algae. Under blue light stimulation, it can act as a cation channel, allowing positively charged ions (mainly sodium ions and a small amount of potassium ions) to enter the cell, which can trigger depolarization of the cell membrane, eventually causing neurons to discharge [3]. In contrast, Halorhodopsin from Natronomonas pharaonis (NpHR) is a chloride pump, that promotes chloride entry into cells under yellow light, causing hyperpolarization of the cell membrane, thereby inhibiting neuron activity.

In this way, researchers are able to control the activity patterns of neurons with unprecedented precision, which is essential for understanding complex neural circuit functions and their role in healthy and disease states. Optogenetics not only provides powerful tools for neuroscience, but also shows great potential in exploring treatments for neurodegenerative disorders, psychiatric disorders, and other diseases associated with dysfunctional brain function.

2.2. Development history of optogenetics

The concept of optogenetics was proposed by several pioneering scientists in the early 21st century, including the work of Edward S. Boyden and Karl Deisseroth et al., who began to explore the possibility of using light-sensitive proteins to precisely manipulate neuronal activity, around 2005 [1]. The advent of this technology has revolutionized the methodology of neuroscience research, enabling researchers to control neuronal activity with unprecedented precision and spatiotemporal resolution, allowing for a deeper understanding of the brain's working mechanism [2].

Initially, optogenetic applications were focused on easily operational small model organisms, such as Drosophila and Caenorhabditis elegans . These organisms are the ideal object for testing new technologies due to their short life cycle, relatively simple genome, and easy genetic manipulation[3]. However, optogenetics developed much faster than expected and was soon extended to more complex mammalian models, especially in rodents, such as mouse and rats [4]. This marks the new stage of optogenetics in the study of brain function in higher organisms.

Over time, the adoptation field of optogenetics has expanded, not only in basic neuroscience research, but also in clinical medicine. For example, optogenetics has shown great potential for [5] PD, depression, and other disorders associated with neuromodulation deregulation. Although there are still challenges such as the selection of gene carriers, immune response and long-term safety in human applications, researchers are making unremitting efforts to overcome these obstacles through technological innovation and promote optogenetics technology to better serve human health [6].

In short, optogenetics, as an emerging and rapidly developing field, has played a pivotal role in neuroscience and behavioral research, and with the continuous progress of technology, the future application prospects in medical practice will become broader.

3. Application of Optogenetics in Neuroscientific Research

3.1. Control and record neuronal activity

Optogenetics provides a revolutionary platform for neuroscience research, allowing researchers to control and record the activity of neurons with unprecedented precision. Introducing light-sensitive proteins into target neurons, gives scientists the ability to use light pulses to activate or inhibit specific neurons, enabling high levels of precise control of neural activity in time and space.

With optogenetics, researchers can delve into the role of individual or population neurons in cognitive processes. For example, when studying higher cognitive functions such as perception, decision-making, learning, and memory, optogenetic techniques allow scientists to accurately activate or inhibit a certain type or group of neurons, in order to see how these interventions affect brain function and behavioral output. This precise control provides a powerful research tool to resolve complex brain networks, helping to better understand the basic working mechanisms of the brain [8].

A specific example is the study of dopaminergic neurons. The dopaminergic system plays a central role in motivation, reward processing, and emotion regulation. Using optogenetic approaches, researchers can specifically activate or silence these neurons, studying how they influence an individual's behavioral choices, such as the response to reward, or coping strategies in stressful situations. Such an experimental design could help scientists identify which neural pathways are involved in specific cognitive or emotional processing, and further explore the psychiatric or neurodegenerative diseases that abnormalities in these pathways may cause [9].

Optogenetics has also facilitated interdisciplinary collaboration, for example in conjunction with computational neuroscience to predict neural network dynamics following optogenetics intervention. This approach not only deepens the author's understanding of brain complexity, but also lays a solid theoretical foundation for the development of novel therapies for neurological diseases in the future. In conclusion, optogenetics, with its unique precision and functionality, has become an integral part of modern neuroscience research, greatly driving the author's understanding of the relationship between brain and behavior.

3.2. The treatment methods for neurological diseases

Optogenetics offers new avenues for understanding neurological disorders and may provide strategies for future therapies. By applying optogenetic techniques in disease models, researchers are able to gain more insight into the specific mechanisms of disease and attempt to alleviate symptoms by regulating specific neuronal populations. Activation or inhibition of specific neurons in the basal ganglia region by optogenetic approaches in PD model animals could significantly improve of core symptoms such as motor disorders[7]. In addition, optogenetics is also used to study the pathologic mechanisms and potential therapies for mental disorders such as post-traumatic stress D disorder (PTSD) [8]. By simulating optogenetic interventions after a traumatic experience, researchers are able to evaluate the role of different neural loops in emotion regulation, thus providing a rationale for the development of effective treatment options.

Optogenetic techniques are not limited to basic research, and their potential clinical applications are also being explored. Despite the challenges of direct optogenetics in humans, such as the safety and long-term effects of gene delivery, optogenetics is expected to become an important part of the treatment of neurological diseases in the future.

4. Application of Optogenetics in Behavioral Science

4.1. Manipulated cellular photoreceptors and behavioral studies

Through the precise manipulation of intracellular photoreceptors, optogenetic techniques have emerged as a key tool to uncover the neural mechanisms underlying complex behaviors. The researchers were able to explore their role in different behaviors by introducing photosensitive proteins into specific neurons and then using light pulses to precisely activate or inhibit these cells [9]. For example, in zebrafish, optogenetic approaches are used to study the neurobiological basis of olfactory responses, by activating or inhibiting specific olfactory receptor neurons where researchers can observe changes in animal behavior to infer the function of these neurons. This approach is not limited to simple reflex behaviors but can be extended to the study of more complex social interactions and courtship behaviors [9].

4.2. Mechanism of learning and memory

Optogenetic techniques are also widely used in the research field of learning and memory, helping scientists to gain a deeper understanding of the neural loops in these processes. Using optogenetic means, researchers can precisely activate or inhibit related neurons during learning, and turn see how these interventions affect memory formation and store [10]. For example, it has been shown that mouse spontaneous behavioral experiments in family cages can be effectively intervened and analyzed by optogenetic methods, and these experimental designs allow the observation and recording of animal learning behavior in a natural environment. This non-invasive approach provides a unique insight into the dynamic processes of learning and memory[11].

4.3. Behavioral treatment for neurological diseases

In addition to basic research, optogenetics has shown great potential in exploring behavioral therapy for neurological disorders. With optogenetic techniques, researchers were able to simulate the symptoms of certain neurological disorders in live animal models and test different treatments [12]. For example, in neuroplasticity studies in the auditory system, optogenetic techniques have been used to induce and study adaptive changes in neurons [13]. Activation of specific auditory pathways by optogenetic means was found to promote neuronal reorganization to improve recovery after hearing loss [14].

In addition, optogenetic methods can achieve precise control of specific areas of the brain, thus providing new ideas for the treatment of conditions such as hemiplegia [15]. For example, in studying the recovery of patients with hemiplegia, optogenetic techniques are used to restore functional connectivity in damaged areas, which opens up new possibilities for future clinical treatments [16]. Although most of these applications are currently still in the laboratory stage, the development of optogenetic technologies undoubtedly holds promise for the treatment of neurological disorders.

5. Conclusion

Optogenetics, a revolutionary technology in neuroscience that combines genetic engineering with optical technology, has become an important tool for studying the function of the nervous system and behavioral phenomena. It provides new ways to understand neural circuits and their roles in disease and healthy disease states.

This paper combines the comprehensive discussion and combing of the definition, principle, and development history of optogenetic technology and its specific application in neuroscience and behavioral research. Optogenetics, as a revolutionary technique that combines genetic engineering with optical technology, has become an important tool for studying the functional and behavioral phenomena of the nervous system. It not only makes it possible to precisely activate or inhibit specific types of neurons, thus revealing their role in higher cognitive functions, but, combined with computational neurology, deepens our understanding of the dynamic changes of brain networks, laying the foundation for the development of new therapeutic strategies.

In behavioral studies, optogenetics deeply explores the neural mechanisms underlying different behaviors by manipulating intracellular photoreceptors and, in particular, provides new ways to study affective states such as anxiety and fear conditioning. Moreover, optogenetics also shows great potential in the treatment of neurological diseases, relieving symptoms by regulating specific neuronal populations and providing a rationale for the development of effective treatment options.

However, the number of literature collected in this paper is limited, so the discussion on the practical application effects and long-term impact of optogenetic technology may be limited based on the existing literature review. Nevertheless, optogenetic technology still faces challenges such as light transmission efficiency, gene delivery safety, and long-term expression stability, which are the focus of future research to better use optogenetic technology to serve human health.


References

[1]. Glock Caspar, Nagpal Jatin & Gottschalk Alexander. (2015). Microbial Rhodopsin Optogenetic Tools: Application for Analyses of Synaptic Transmission and of Neuronal Network Activity in Behavior. Methods in molecular biology (Clifton, N J) 87-103.

[2]. Guo Songchao. (2015). Research on Rat Robot Motion Regulation Based on Optogenetics Technology (PhD dissertation, Zhejiang University).PhD.https://kns.cnki.net/kcms2/article/abstract?v=5iIAKlsf9WDUCrNLJBlFflH58CN6Gy8CftcyMZx9qWhEa4yD72GSwTN-qPbu3sqUBFFyMJLkibKkDh-C_IAsmiTMdQxk0r8UFfr-Em4sKtdF3QVU8pGdjs7msYxwGxOxHBra5OyHfYm6kJMI3TaZ2o-R-92ExhUmO23hzxpEbWbCHMPttGqvVACzzrIkY86SAR9jSaEg1OY=&uniplatform=NZKPT&language=CHS

[3]. Fang-Yen Christopher, Alkema Mark J & Samuel Aravinthan D T. (2015). Illuminating neural circuits and behaviour in Caenorhabditis elegans with optogenetics.. Philosophical transactions of the Royal Society of London. Series B, Biological sciences (1677), 20140212.

[4]. Chen Ting, Song Huiqiong, Zhang Zongze, Zhou Lingxue & Zou Yufeng. (2015). Research progress of optogenetics technology applied in animal ethology in neural circuits. International Journal of Psychiatry. (06), 22-25. doi:10.13479/j.cnki.jip.2015.06.008.

[5]. Roberts Bradley M, Jarrin Sarah E, Mathur Brian N & Bailey Aileen M. (2016). Illuminating the Undergraduate Behavioral Neuroscience Laboratory: A Guide for the in vivo Application of Optogenetics in Mammalian Model Organisms Journal of undergraduate neuroscience education : JUNE : a publication of FUN, Faculty for Undergraduate Neuroscience (2), A111-6.

[6]. Bi Mingxuan. (2024). Basic Research on the Regulation of Pigeon Movement Based on Electrical Stimulation and Optogenetics (Master's thesis, Qilu University of Technology). Master's degree. https://link.cnki.net/doi/10.27278/d.cnki.gsdqc.2024.001006.doi:10.27278/d.cnki.gsdqc.2024.001006.

[7]. Anderson Kevin A, Whitehead Bailey J, Petersen Eric D, Kemme Madison R, Wedster Anna, Hochgeschwender Ute & Sandstrom Michael I. (2022). Behavioral Context Improves Optogenetic Stimulation of Transplanted Dopaminergic Cells in Unilateral 6-OHDA Rats.. Behavioural brain research 114279

[8]. Al Abed Alice Shaam, Sellami Azza, Ducourneau Eva-Gunnel, Bouarab Chloé, Marighetto Aline & Desmedt Aline. (2021). Protocols to Induce, Prevent, and Treat Post-traumatic Stress Disorder-like Memory in Mice: Optogenetics and Behavioral Approaches. Bio-protocol (19), e4174

[9]. Jeong YunMi, Choi TaeIk, Hwang KyuSeok, Lee JeongSoo, Gerlai Robert & Kim CheolHee. (2021). Optogenetic Manipulation of Olfactory Responses in Transgenic Zebrafish: A Neurobiological and Behavioral Study. International Journal of Molecular Sciences (13), 7191

[10]. Wei Mengxia. (2021). Research on the Function of Vestibular Nucleus Using Optogenetics and Neural Circuit Tracing Techniques (Master's thesis, University of Chinese Academy of Sciences (Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences)). Master's degree.https://link.cnki.net/doi/10.27822/d.cnki.gszxj.2021.000055 doi:10.27822/d.cnki.gszxj.2021.000055.

[11]. Hao Yaoyao, Thomas Alyse Marian & Li Nuo. (2021). Fully autonomous mouse behavioral and optogenetic experiments in home-cage. eLife

[12]. (2020). Life Science Research - Enzyme Research; Studies from University of North Carolina in the Area of Enzyme Research Described (Optogenetic perturbation of the biochemical pathways that control cell behavior). Chemicals & Chemistry

[13]. Li Fei. (2016). Inducing Neuroplasticity in the Auditory System through Optogenetic Stimulation (PhD thesis, University of Science and Technology of China). PhD. https://link.cnki.net/doi/10.27517/d.cnki.gzkju.2016.000009.doi:10.27517/d.cnki.gzkju.2016.000009.

[14]. K. Janitzky, M. Lippert, J. Tegtmeier, H.-J. Heinze & F.W. Ohl. (2016). EP 56. Optogenetic control of the locus coeruleus in mice: Behavioral and electrophysiological data. Clinical Neurophysiology (9), e198

[15]. Dygalo N N. (2015). [Optogenetics in Investigations of Brain Mechanisms of Behavior].. Uspekhi fiziologicheskikh nauk (2), 17-23.

[16]. Jiang Su. (2014). In Vivo Optogenetics-Electrophysiology Combined Study on Brain Functional Remodeling Mechanism of Bilateral Upper Limb Movement Controlled by Lateral Hemisphere (PhD thesis, Fudan University). PhD. https://kns.cnki.net/kcms2/article/abstract?v=5iIAKlsf9WAu7LBLsQArMlO0XJ8qTGo_Q9C6JI5v6V326ROxLADM1--Jb26ty62C_WuEybrzm_IjQgQqONPkcFV5swOWtNjcovVxqz0mvt0_vuYLyD1a_fxPr6Ii3lLhMFdVUAta0brS5RN7YZ0oFbE8DMIJPOMQHCCNPZMpCeEfTmKFo8uKvSQoA_s2JNaW93U_bRAnlxA=&uniplatform=NZKPT&language=CHS


Cite this article

Xu,Q. (2024). The Application Progress of Optogenetics in Neuroscience and Behavioral Studies. Theoretical and Natural Science,66,108-113.

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Volume title: Proceedings of the 4th International Conference on Biological Engineering and Medical Science

ISBN:978-1-83558-763-8(Print) / 978-1-83558-764-5(Online)
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References

[1]. Glock Caspar, Nagpal Jatin & Gottschalk Alexander. (2015). Microbial Rhodopsin Optogenetic Tools: Application for Analyses of Synaptic Transmission and of Neuronal Network Activity in Behavior. Methods in molecular biology (Clifton, N J) 87-103.

[2]. Guo Songchao. (2015). Research on Rat Robot Motion Regulation Based on Optogenetics Technology (PhD dissertation, Zhejiang University).PhD.https://kns.cnki.net/kcms2/article/abstract?v=5iIAKlsf9WDUCrNLJBlFflH58CN6Gy8CftcyMZx9qWhEa4yD72GSwTN-qPbu3sqUBFFyMJLkibKkDh-C_IAsmiTMdQxk0r8UFfr-Em4sKtdF3QVU8pGdjs7msYxwGxOxHBra5OyHfYm6kJMI3TaZ2o-R-92ExhUmO23hzxpEbWbCHMPttGqvVACzzrIkY86SAR9jSaEg1OY=&uniplatform=NZKPT&language=CHS

[3]. Fang-Yen Christopher, Alkema Mark J & Samuel Aravinthan D T. (2015). Illuminating neural circuits and behaviour in Caenorhabditis elegans with optogenetics.. Philosophical transactions of the Royal Society of London. Series B, Biological sciences (1677), 20140212.

[4]. Chen Ting, Song Huiqiong, Zhang Zongze, Zhou Lingxue & Zou Yufeng. (2015). Research progress of optogenetics technology applied in animal ethology in neural circuits. International Journal of Psychiatry. (06), 22-25. doi:10.13479/j.cnki.jip.2015.06.008.

[5]. Roberts Bradley M, Jarrin Sarah E, Mathur Brian N & Bailey Aileen M. (2016). Illuminating the Undergraduate Behavioral Neuroscience Laboratory: A Guide for the in vivo Application of Optogenetics in Mammalian Model Organisms Journal of undergraduate neuroscience education : JUNE : a publication of FUN, Faculty for Undergraduate Neuroscience (2), A111-6.

[6]. Bi Mingxuan. (2024). Basic Research on the Regulation of Pigeon Movement Based on Electrical Stimulation and Optogenetics (Master's thesis, Qilu University of Technology). Master's degree. https://link.cnki.net/doi/10.27278/d.cnki.gsdqc.2024.001006.doi:10.27278/d.cnki.gsdqc.2024.001006.

[7]. Anderson Kevin A, Whitehead Bailey J, Petersen Eric D, Kemme Madison R, Wedster Anna, Hochgeschwender Ute & Sandstrom Michael I. (2022). Behavioral Context Improves Optogenetic Stimulation of Transplanted Dopaminergic Cells in Unilateral 6-OHDA Rats.. Behavioural brain research 114279

[8]. Al Abed Alice Shaam, Sellami Azza, Ducourneau Eva-Gunnel, Bouarab Chloé, Marighetto Aline & Desmedt Aline. (2021). Protocols to Induce, Prevent, and Treat Post-traumatic Stress Disorder-like Memory in Mice: Optogenetics and Behavioral Approaches. Bio-protocol (19), e4174

[9]. Jeong YunMi, Choi TaeIk, Hwang KyuSeok, Lee JeongSoo, Gerlai Robert & Kim CheolHee. (2021). Optogenetic Manipulation of Olfactory Responses in Transgenic Zebrafish: A Neurobiological and Behavioral Study. International Journal of Molecular Sciences (13), 7191

[10]. Wei Mengxia. (2021). Research on the Function of Vestibular Nucleus Using Optogenetics and Neural Circuit Tracing Techniques (Master's thesis, University of Chinese Academy of Sciences (Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences)). Master's degree.https://link.cnki.net/doi/10.27822/d.cnki.gszxj.2021.000055 doi:10.27822/d.cnki.gszxj.2021.000055.

[11]. Hao Yaoyao, Thomas Alyse Marian & Li Nuo. (2021). Fully autonomous mouse behavioral and optogenetic experiments in home-cage. eLife

[12]. (2020). Life Science Research - Enzyme Research; Studies from University of North Carolina in the Area of Enzyme Research Described (Optogenetic perturbation of the biochemical pathways that control cell behavior). Chemicals & Chemistry

[13]. Li Fei. (2016). Inducing Neuroplasticity in the Auditory System through Optogenetic Stimulation (PhD thesis, University of Science and Technology of China). PhD. https://link.cnki.net/doi/10.27517/d.cnki.gzkju.2016.000009.doi:10.27517/d.cnki.gzkju.2016.000009.

[14]. K. Janitzky, M. Lippert, J. Tegtmeier, H.-J. Heinze & F.W. Ohl. (2016). EP 56. Optogenetic control of the locus coeruleus in mice: Behavioral and electrophysiological data. Clinical Neurophysiology (9), e198

[15]. Dygalo N N. (2015). [Optogenetics in Investigations of Brain Mechanisms of Behavior].. Uspekhi fiziologicheskikh nauk (2), 17-23.

[16]. Jiang Su. (2014). In Vivo Optogenetics-Electrophysiology Combined Study on Brain Functional Remodeling Mechanism of Bilateral Upper Limb Movement Controlled by Lateral Hemisphere (PhD thesis, Fudan University). PhD. https://kns.cnki.net/kcms2/article/abstract?v=5iIAKlsf9WAu7LBLsQArMlO0XJ8qTGo_Q9C6JI5v6V326ROxLADM1--Jb26ty62C_WuEybrzm_IjQgQqONPkcFV5swOWtNjcovVxqz0mvt0_vuYLyD1a_fxPr6Ii3lLhMFdVUAta0brS5RN7YZ0oFbE8DMIJPOMQHCCNPZMpCeEfTmKFo8uKvSQoA_s2JNaW93U_bRAnlxA=&uniplatform=NZKPT&language=CHS