Optogenetics has revolutionized the field of neuroscience by enabling precise control of neural activity through light-sensitive proteins known as opsins.This review article discusses the fundamental principles of opt...Optogenetics has revolutionized the field of neuroscience by enabling precise control of neural activity through light-sensitive proteins known as opsins.This review article discusses the fundamental principles of optogenetics,including the activation of both excitatory and inhibitory opsins,as well as the development of optogenetic models that utilize recombinant viral vectors.A considerable portion of the article addresses the limitations of optogenetic tools and explores strategies to overcome these challenges.These strategies include the use of adeno-associated viruses,cell-specific promoters,modified opsins,and methodologies such as bioluminescent optogenetics.The application of viral recombinant vectors,particularly adeno-associated viruses,is emerging as a promising avenue for clinical use in delivering opsins to target cells.This trend indicates the potential for creating tools that offer greater flexibility and accuracy in opsin delivery.The adaptations of these viral vectors provide advantages in optogenetic studies by allowing for the restricted expression of opsins through cell-specific promoters and various viral serotypes.The article also examines different cellular targets for optogenetics,including neurons,astrocytes,microglia,and Schwann cells.Utilizing specific promoters for opsin expression in these cells is essential for achieving precise and efficient stimulation.Research has demonstrated that optogenetic stimulation of both neurons and glial cells-particularly the distinct phenotypes of microglia,astrocytes,and Schwann cells-can have therapeutic effects in neurological diseases.Glial cells are increasingly recognized as important targets for the treatment of these disorders.Furthermore,the article emphasizes the emerging field of bioluminescent optogenetics,which combines optogenetic principles with bioluminescent proteins to visualize and manipulate neural activity in real time.By integrating molecular genetics techniques with bioluminescence,researchers have developed methods to monitor neuronal activity efficiently and less invasively,enhancing our understanding of central nervous system function and the mechanisms of plasticity in neurological disorders beyond traditional neurobiological methods.Evidence has shown that optogenetic modulation can enhance motor axon regeneration,achieve complete sensory reinnervation,and accelerate the recovery of neuromuscular function.This approach also induces complex patterns of coordinated motor neuron activity and promotes neural reorganization.Optogenetic approaches hold immense potential for therapeutic interventions in the central nervous system.They enable precise control of neural circuits and may offer new treatments for neurological disorders,particularly spinal cord injuries,peripheral nerve injuries,and other neurodegenerative diseases.展开更多
Optogenetics is a newly-introduced technology in the life sciences and is gaining increasing attention.It refers to the combination of optical technologies and genetic methods to control the activity of specific cell ...Optogenetics is a newly-introduced technology in the life sciences and is gaining increasing attention.It refers to the combination of optical technologies and genetic methods to control the activity of specific cell groups in living tissue,during which high-resolution spatial and temporal manipulation of cells is achieved.Optogenetics has been applied to numerous regions,including cerebral cortex,hippocampus,ventral tegmental area,nucleus accumbens,striatum,spinal cord,and retina,and has revealed new directions of research in neuroscience and the treatment of related diseases.Since optogenetic tools are controllable at high spatial and temporal resolution,we discuss its applications in these regions in detail and the recent understanding of higher brain functions,such as reward-seeking,learning and memory,and sleep.Further,the possibilities of improved utility of this newly-emerging technology are discussed.We intend to provide a paradigm of the latest advances in neuroscience using optogenetics.展开更多
We have delivered viral vectors containing either Chop2 fused with GFP, Channelrhodopsin-2 （ChR2）, or Halorhodopsin （HaloR） fused with mCherry （to form light gated cation channels or chloride pumps, respectively...We have delivered viral vectors containing either Chop2 fused with GFP, Channelrhodopsin-2 （ChR2）, or Halorhodopsin （HaloR） fused with mCherry （to form light gated cation channels or chloride pumps, respectively）, into the dorsal cochlear nucleus （DCN）. One to eighteen months later we examined the CN and inferior colliculus （IC） for evidence of virally transfected cells and processes. Production of ChR2 and HaloR was observed throughout the DCN. Rhodopsin localization within neurons was determined, with elongate, fusiform and giant cells identified based on morphology and location within the DCN. Production of ChR2 and HaloR was found at both the injection site as well as in regions projecting to and from the DCN. Light driven neuronal activity in the DCN was dependent upon the wavelength and intensity of the light, with only the appropriate wavelength resulting in activation and higher intensity light resulting in more neuronal activity. Transfecting cells via viral delivery of rhodopsins can be useful as a tract tracer and as a neuronal marker to delineate pathways. In the future rhodopsin delivery and activation may be developed as an alternative to electrical stimulation of neurons.展开更多
基金supported by a grant from the Russian Science Foundation,No.23-75-10041(to MY)。
文摘Optogenetics has revolutionized the field of neuroscience by enabling precise control of neural activity through light-sensitive proteins known as opsins.This review article discusses the fundamental principles of optogenetics,including the activation of both excitatory and inhibitory opsins,as well as the development of optogenetic models that utilize recombinant viral vectors.A considerable portion of the article addresses the limitations of optogenetic tools and explores strategies to overcome these challenges.These strategies include the use of adeno-associated viruses,cell-specific promoters,modified opsins,and methodologies such as bioluminescent optogenetics.The application of viral recombinant vectors,particularly adeno-associated viruses,is emerging as a promising avenue for clinical use in delivering opsins to target cells.This trend indicates the potential for creating tools that offer greater flexibility and accuracy in opsin delivery.The adaptations of these viral vectors provide advantages in optogenetic studies by allowing for the restricted expression of opsins through cell-specific promoters and various viral serotypes.The article also examines different cellular targets for optogenetics,including neurons,astrocytes,microglia,and Schwann cells.Utilizing specific promoters for opsin expression in these cells is essential for achieving precise and efficient stimulation.Research has demonstrated that optogenetic stimulation of both neurons and glial cells-particularly the distinct phenotypes of microglia,astrocytes,and Schwann cells-can have therapeutic effects in neurological diseases.Glial cells are increasingly recognized as important targets for the treatment of these disorders.Furthermore,the article emphasizes the emerging field of bioluminescent optogenetics,which combines optogenetic principles with bioluminescent proteins to visualize and manipulate neural activity in real time.By integrating molecular genetics techniques with bioluminescence,researchers have developed methods to monitor neuronal activity efficiently and less invasively,enhancing our understanding of central nervous system function and the mechanisms of plasticity in neurological disorders beyond traditional neurobiological methods.Evidence has shown that optogenetic modulation can enhance motor axon regeneration,achieve complete sensory reinnervation,and accelerate the recovery of neuromuscular function.This approach also induces complex patterns of coordinated motor neuron activity and promotes neural reorganization.Optogenetic approaches hold immense potential for therapeutic interventions in the central nervous system.They enable precise control of neural circuits and may offer new treatments for neurological disorders,particularly spinal cord injuries,peripheral nerve injuries,and other neurodegenerative diseases.
基金supported by the National Basic Research Program of China (2011CB503700)
文摘Optogenetics is a newly-introduced technology in the life sciences and is gaining increasing attention.It refers to the combination of optical technologies and genetic methods to control the activity of specific cell groups in living tissue,during which high-resolution spatial and temporal manipulation of cells is achieved.Optogenetics has been applied to numerous regions,including cerebral cortex,hippocampus,ventral tegmental area,nucleus accumbens,striatum,spinal cord,and retina,and has revealed new directions of research in neuroscience and the treatment of related diseases.Since optogenetic tools are controllable at high spatial and temporal resolution,we discuss its applications in these regions in detail and the recent understanding of higher brain functions,such as reward-seeking,learning and memory,and sleep.Further,the possibilities of improved utility of this newly-emerging technology are discussed.We intend to provide a paradigm of the latest advances in neuroscience using optogenetics.
基金supported by Ralph Wilson Foundation(to A.G.H)Capita Foundation(to A.G.H)
文摘We have delivered viral vectors containing either Chop2 fused with GFP, Channelrhodopsin-2 （ChR2）, or Halorhodopsin （HaloR） fused with mCherry （to form light gated cation channels or chloride pumps, respectively）, into the dorsal cochlear nucleus （DCN）. One to eighteen months later we examined the CN and inferior colliculus （IC） for evidence of virally transfected cells and processes. Production of ChR2 and HaloR was observed throughout the DCN. Rhodopsin localization within neurons was determined, with elongate, fusiform and giant cells identified based on morphology and location within the DCN. Production of ChR2 and HaloR was found at both the injection site as well as in regions projecting to and from the DCN. Light driven neuronal activity in the DCN was dependent upon the wavelength and intensity of the light, with only the appropriate wavelength resulting in activation and higher intensity light resulting in more neuronal activity. Transfecting cells via viral delivery of rhodopsins can be useful as a tract tracer and as a neuronal marker to delineate pathways. In the future rhodopsin delivery and activation may be developed as an alternative to electrical stimulation of neurons.
