Optogenetics:a novel optical manipulation tool for medical investigation

Optogenetics is a new and rapidly evolving gene and neuroengineering technology that allows optical control of specific populations of neurons without affecting other neurons in the brain at high temporal and spatial resolution. By heterologous expression of the light-sensitive membrane proteins, cell type-specific depolarization or hyperpolarization can be optically induced on a millisecond time scale. Optogenetics has the higher selectivity and specificity compared to traditional electrophysiological techniques and pharmaceutical methods. It has been a novel promising tool for medical research. Because of easy handling, high temporal and spatial precision, optogenetics has been applied to many aspects of nervous system research, such as tactual neural circuit, visual neural circuit, auditory neural circuit and olfactory neural circuit, as well as research of some neurological diseases. The review highlights the recent advances of optogenetics in medical study.

Enhance sensitivity to illumination and synchronization in light-dependent neurons

When a phototube is activated to connect a neural circuit,the output voltage becomes sensitive to external illumination because the photocurrent across the phototube can be controlled by external electromagnetic wave.The channel currents from different branch circuits have different impacts on the outputs voltage of the neural circuit.In this paper,a phototube is incorporated into different branch circuits in a simple neural circuit,and then a light-controlled neuron is obtained for further nonlinear analysis.Indeed,the phototube is considered as exciting source when it is activated by external illumination,and two kinds of light-sensitive neurons are obtained when the phototube is connected to capacitor or induction coil,respectively.Electric synapse coupling is applied to detect possible synchronization between two functional neurons,and the energy consumption along the coupling channel via resistor is estimated.The analog circuits for the two kinds of lightsensitive neurons are supplied for further confirmation by using Multisim.It is found that two light-sensitive neurons and neural circuits can be synchronized by taming the coupling intensity carefully.It provides possible clues to understand the synchronization mechanism for eyes and artificial sensors which are sensitive to illumination.Finally,a section for open problems is supplied for further investigation about its collective behaviors in the network with/without synapse coupling.

Wave filtering and firing modes in a light-sensitive neural circuit

Inspired by the photoelectric effect,a phototube is incorporated into a simple neural circuit,and then the output voltage and dynamics become sensitive to external illumination within a specific frequency band.The firing modes are also dependent on the amplitude and frequency band in the illumination.In this paper,the signal outputs from a chaotic circuit are used as external optical signals,which are filtered and encoded by a phototube.Then,the functional neural circuit is excited to present a variety of firing modes and patterns.An exponential function of the filtering wave is proposed to discover the biophysical mechanism for frequency selection in the retina as most of wave bands of the external illumination are absorbed in the cathode material of the phototube while a specific band is effective in inducing a photocurrent for stimulating the visual neurons.Based on our light-sensitive neural circuit and model,external illumination is filtered and firing modes in the neuron are reproduced;furthermore,the mode transition induced by parameter shift is also investigated in detail.This result discovers the signal processing mechanism in the visual neurons and provides helpful guidance for designing artificial sensors for encoding optical signals and for repairing abnormalities in the retina of the visual system.

Optogenetic activation of intracellular signaling based on light-inducible protein-protein homo-interactions

Dynamic protein-protein interactions are essential for proper cell functioning.Homointeraction events—physical interactions between the same type of proteins—represent a pivotal subset of protein-protein interactions that are widely exploited in activating intracellular signaling pathways.Capacities of modulating protein-protein interactions with spatial and temporal resolution are greatly desired to decipher the dynamic nature of signal transduction mechanisms.The emerging optogenetic technology,based on genetically encoded light-sensitive proteins,provides promising opportunities to dissect the highly complex signaling networks with unmatched specificity and spatiotemporal precision.Here we review recent achievements in the development of optogenetic tools enabling light-inducible protein-protein homo-interactions and their applications in optical activation of signaling pathways.

Prodrugs of hydrogen sulfide and related sulfur species: recent development

Hydrogen sulfide(H2S) is commonly referred to as the third gasotransmitter with firmly established physiological roles. Prodrug approaches have been broadly applied to deliver H2S for various applications and mechanistic studies. Since S-persulfidation and glutathionylation are known to be important in cellular signaling by sulfur species, there have been interests in developing donors of persulfide and glutathione persulfide as well. In this review, we discuss the recent development in area of prodrugs for various sulfur species.

Nanoliposome-encapsulated caged-GABA for modulating neural electrophysiological activity with simultaneous detection by microelectrode arrays

Effective and precise neural modulation with real-time detection in the brain is of great importance and represents a significant challenge.Nanoliposome-encapsulated light-sensitive compounds have excellent characteristics such as high temporal and spatial resolution,delayed drug clearance,and restricted drug biodistribution for neural modulation.In this study,we developed a nanoliposome-based delivery system for ruthenium-based caged GABA compounds(Nanolipo-Ru)to modulate neural activity and allow for real-time monitoring using the microelectrode arrays(MEAs).The Nanolipo-Ru nanoparticles had an average size of 134.10±4.30 nm and exhibited excellent stability for seven weeks.For the in vivo experiment in the rat,release of GABA by Nanolipo-Ru under blue light illumination resulted in an average firing rate reduction in interneurons and pyramidal neurons in the same brain region of 79.4%and 81.6%,respectively.Simultaneously,the average power of local field potentials in the 0–15 Hz range degraded from 4.34 to 0.85 mW.In addition,the Nanolipo-Ru nanoparticles have the potential to provide more flexible timing of modulation than unencapsulated RuBi-GABA in the experiments.These results indicated that Nanolipo-Ru could be an effective platform for regulating neuronal electrophysiology.Furthermore,nanoliposomes with appropriate modifications would render promising utilities for targeting of specific types of neurons in the future.