No abstract available.
Optogenetics* ; Urology*

Optogenetics ; Vision, Ocular

Chronic pain represents a major clinical issue which so far is still in shortage of selective and effective treatment. Multiple components are involved in the pain processing, including peripheral, spinal and supraspinal levels of the nervous system. The core to fight the pain problem effectively is to have a good understanding of nociceptive mechanism and the neurobiology of pain perception. Optogenetic technique allows selective activation of subpopulation neurons and provides possibility for better understanding of complex pathway and modulation mechanism in nervous system. Here we review the researches to date that used optogenetic tools for studying pain pathway, and we also provide a brief overview of some new development in optogenetic techniques that may have great potentials in pain research.
Chronic Pain ; Humans ; Neurons ; Optogenetics ; Pain

Dynamic variations of the cell microenvironment can affect cell differentiation, cell signaling pathways, individual growth, and disease. Optogenetics combines gene-encoded protein expression with optical controlling, and offers a novel, reversible, non-invasive and spatiotemporal-specific research tool to dynamically or reversibly regulate cell signaling pathways, subcellular localization and gene expression. This review summarizes the types of optogenetic components and the involved cellular signaling pathways, and explores the application and future prospects of the light-controlled cell signaling pathways.
Cell Differentiation ; Light ; Optogenetics ; Proteins ; Signal Transduction

The brain consists of heterogeneous populations of neuronal and non-neuronal cells. The revelation of their connections and interactions is fundamental to understanding normal brain functions as well as abnormal changes in pathological conditions. Optogenetics and chemogenetics have been developed to allow functional manipulations both in vitro and in vivo to examine causal relationships between cellular changes and functional outcomes. These techniques are based on genetically encoded effector molecules that respond exclusively to exogenous stimuli, such as a certain wavelength of light or a synthetic ligand. Activation of effector molecules provokes diverse intracellular changes, such as an influx or efflux of ions, depolarization or hyperpolarization of membranes, and activation of intracellular signaling cascades. Optogenetics and chemogenetics have been applied mainly to the study of neuronal circuits, but their use in studying non-neuronal cells has been gradually increasing. Here we introduce recent studies that have employed optogenetics and chemogenetics to reveal the function of astrocytes and gliotransmitters.
Astrocytes* ; Brain ; In Vitro Techniques ; Ions ; Membranes ; Neurons ; Optogenetics*

Chronic pain relief remains an unmet medical need. Current research points to a substantial contribution of glia-neuron interaction in its pathogenesis. Particularly, microglia play a crucial role in the development of chronic pain. To better understand the microglial contribution to chronic pain, specific regional and temporal manipulations of microglia are necessary. Recently, two new approaches have emerged that meet these demands. Chemogenetic tools allow the expression of designer receptors exclusively activated by designer drugs (DREADDs) specifically in microglia. Similarly, optogenetic tools allow for microglial manipulation via the activation of artificially expressed, light-sensitive proteins. Chemo- and optogenetic manipulations of microglia in vivo are powerful in interrogating microglial function in chronic pain. This review summarizes these emerging tools in studying the role of microglia in chronic pain and highlights their potential applications in microglia-related neurological disorders.
Humans ; Optogenetics ; Brain/physiology* ; Microglia ; Chronic Pain/therapy* ; Neurons/physiology*

Pain is an unpleasant sensory and emotional experience associated with, or resembling that associated with, actual or potential tissue damage. The processing of pain involves complicated modulation at the levels of the periphery, spinal cord, and brain. The pathogenesis of chronic pain is still not fully understood, which makes the clinical treatment challenging. Optogenetics, which combines optical and genetic technologies, can precisely intervene in the activity of specific groups of neurons and elements of the related circuits. Taking advantage of optogenetics, researchers have achieved a body of new findings that shed light on the cellular and circuit mechanisms of pain transmission, pain modulation, and chronic pain both in the periphery and the central nervous system. In this review, we summarize recent findings in pain research using optogenetic approaches and discuss their significance in understanding the pathogenesis of chronic pain.
Brain ; Chronic Pain ; Humans ; Neurons ; Optogenetics ; Spinal Cord

Our brains are composed of two distinct cell types: neurons and glia. Emerging data from recent investigations show that glial cells, especially astrocytes and microglia, are able to regulate synaptic transmission and thus brain information processing. This suggests that, not only neuronal activity, but communication between neurons and glia also plays a key role in brain function. Thus, it is currently well known that the physiology and pathophysiology of brain function can only be completely understood by considering the interplay between neurons and glia. However, it has not yet been possible to dissect glial cell type-specific roles in higher brain functions in vivo. Meanwhile, the recent development of optogenetics techniques has allowed investigators to manipulate neural activity with unprecedented temporal and spatial precision. Recently, a series of studies suggested the possibility of applying this cutting-edge technique to manipulate glial cell activity. This review briefly discusses the feasibility of optogenetic glia manipulation, which may provide a technical innovation in elucidating the in vivo role of glial cells in complex higher brain functions.
Astrocytes ; Automatic Data Processing ; Brain ; Humans ; Microglia ; Neuroglia* ; Neurons ; Optogenetics* ; Physiology ; Research Personnel ; Synapses ; Synaptic Transmission

Live imaging has become an essential tool to investigate the coordinated activity and output of cellular networks. Within the last decade, 2 Nobel prizes have been awarded to recognize innovations in the field of imaging: one for the discovery, use, and optimization of the green fluorescent protein (2008) and the second for the development of super-resolved fluorescence microscopy (2014). New advances in both optogenetics and microscopy now enable researchers to record and manipulate activity from specific populations of cells with better contrast and resolution, at higher speeds, and deeper into live tissues. In this review, we will discuss some of the recent developments in microscope technology and in the synthesis of fluorescent probes, both synthetic and genetically encoded. We focus on how live imaging of cellular physiology has progressed our understanding of the control of gastrointestinal motility, and we discuss the hurdles to overcome in order to apply the novel tools in the field of neurogastroenterology and motility.
Awards and Prizes ; Enteric Nervous System ; Fluorescence ; Fluorescent Dyes ; Gastrointestinal Motility ; Microscopy ; Microscopy, Fluorescence ; Optogenetics ; Physiology

Human studies of brain stimulation have demonstrated modulatory effects on the perception of pain. However, whether the primary somatosensory cortical activity is associated with antinociceptive responses remains unknown. Therefore, we examined the antinociceptive effects of neuronal activity evoked by optogenetic stimulation of primary somatosensory cortex. Optogenetic transgenic mice were subjected to continuous or pulse-train optogenetic stimulation of the primary somatosensory cortex at frequencies of 15, 30, and 40 Hz, during a tail clip test. Reaction time was measured using a digital high-speed video camera. Pulse-train optogenetic stimulation of primary somatosensory cortex showed a delayed pain response with respect to a tail clip, whereas no significant change in reaction time was observed with continuous stimulation. In response to the pulse-train stimulation, video monitoring and local field potential recording revealed associated paw movement and sensorimotor rhythms, respectively. Our results show that optogenetic stimulation of primary somatosensory cortex at beta and gamma frequencies blocks transmission of pain signals in tail clip test.
Animals ; Brain ; Humans ; Mice ; Mice, Transgenic ; Neurons ; Optogenetics ; Pain Perception* ; Reaction Time ; Somatosensory Cortex* ; Tail*