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Optogenetic control of integrin-matrix interaction
摘要： Optogenetic approaches have gathered momentum in precisely modulating and interrogating cellular signalling and gene expression. The use of optogenetics on the outer cell surface to interrogate how cells receive stimuli from their environment, however, has so far not reached its full potential. Here we demonstrate the development of an optogenetically regulated membrane receptor-ligand pair exemplified by the optically responsive interaction of an integrin receptor with the extracellular matrix. The system is based on an integrin engineered with a phytochrome-interacting factor domain (OptoIntegrin) and a red light-switchable phytochrome B-functionalized matrix (OptoMatrix). This optogenetic receptor-ligand pair enables light-inducible and -reversible cell-matrix interaction, as well as the controlled activation of downstream mechanosensory signalling pathways. Pioneering the application of optogenetic switches in the extracellular environment of cells, this OptoMatrix–OptoIntegrin system may serve as a blueprint for rendering matrix–receptor interactions amendable to precise control with light.
关键词： Optogenetics,Mechanosensing,Extracellular matrix,Cell adhesion,Integrin
更新于2025-11-21 11:24:58
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Behavior Responses to Chemical and Optogenetic Stimuli in Drosophila Larvae
摘要： An animal’s ability to navigate an olfactory environment is critically dependent on the activities of its first-order olfactory receptor neurons (ORNs). While considerable research has focused on ORN responses to odorants, the mechanisms by which olfactory information is encoded in the activities of ORNs and translated into navigational behavior remain poorly understood. We sought to determine the contributions of most Drosophila melanogaster larval ORNs to navigational behavior. Using odorants to activate ORNs and a larval tracking assay to measure the corresponding behavioral response, we observed that larval ORN activators cluster into four groups based on the behavior responses elicited from larvae. This is significant because it provides new insights into the functional relationship between ORN activity and behavioral response. Subsequent optogenetic analyses of a subset of ORNs revealed previously undescribed properties of larval ORNs. Furthermore, our results indicated that different temporal patterns of ORN activation elicit different behavioral outputs: some ORNs respond to stimulus increments while others respond to stimulus decrements. These results suggest that the ability of ORNs to encode temporal patterns of stimulation increases the coding capacity of the olfactory circuit. Moreover, the ability of ORNs to sense stimulus increments and decrements facilitates instantaneous evaluations of concentration changes in the environment. Together, these ORN properties enable larvae to efficiently navigate a complex olfactory environment. Ultimately, knowledge of how ORN activity patterns and their weighted contributions influence odor coding may eventually reveal how peripheral information is organized and transmitted to subsequent layers of a neural circuit.
关键词： olfactory receptor neuron,Drosophila larva,behavior,olfaction,optogenetics
更新于2025-09-23 15:23:52
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Fast Calculation of Computer Generated Holograms for 3D Photostimulation through Compressive-Sensing Gerchberg–Saxton Algorithm
摘要： The use of spatial light modulators to project computer generated holograms is a common strategy for optogenetic stimulation of multiple structures of interest within a three-dimensional volume. A common requirement when addressing multiple targets sparsely distributed in three dimensions is the generation of a points cloud, focusing excitation light in multiple diffraction-limited locations throughout the sample. Calculation of this type of holograms is most commonly performed with either the high-speed, low-performance random superposition algorithm, or the low-speed, high performance Gerchberg–Saxton algorithm. This paper presents a variation of the Gerchberg–Saxton algorithm that, by only performing iterations on a subset of the data, according to compressive sensing principles, is rendered significantly faster while maintaining high quality outputs. The algorithm is presented in high-efficiency and high-uniformity variants. All source code for the method implementation is available as Supplementary Materials and as open-source software. The method was tested computationally against existing algorithms, and the results were confirmed experimentally on a custom setup for in-vivo multiphoton optogenetics. The results clearly show that the proposed method can achieve computational speed performances close to the random superposition algorithm, while retaining the high performance of the Gerchberg–Saxton algorithm, with a minimal hologram quality loss.
关键词： optogenetics,spatial light modulators,computer generated holograms
更新于2025-09-23 15:23:52
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Analysis of Light Propagation on Physiological Properties of Neurons for Nanoscale Optogenetics
摘要： Miniaturization of implantable devices is an important challenge for future Brain-Computer Interface applications, and in particular for achieving precise neuron stimulation. For stimulation that utilizes light, i.e., optogenetics, the light propagation behavior and interaction at the nanoscale with elements within the neuron is an important factor that needs to be considered when designing the device. This paper analyses the effect of light behavior for a single neuron stimulation, and focuses on the impact from different cell shapes. Based on the Mie Scattering theory, the paper analyzes how the shape of the soma and the nucleus contributes to the focusing effect resulting in an intensity increase, which ensures that neurons can assist in transferring light through the tissue towards the target cells. At the same time, this intensity increase can in turn also stimulate neighboring cells leading to interference within the neural circuits. The paper also analyzes the ideal placements of the device with respect to the angle and position within the cortex that can enable axonal biophoton communications, which can contain light within the cell to avoid interference.
关键词： Optogenetics,Geometrical Optics Analysis,Nano Communications,Mie scattering
更新于2025-09-23 15:23:52
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Near-Infrared-Light Activatable Nanoparticles for Deep-Tissue-Penetrating Wireless Optogenetics
摘要： Optogenetics has been developed to control the activities and functions of cells with high spatiotemporal resolution, cell-type specificity, and flexibility. However, current optogenetic tools generally rely on visible light (e.g., blue or yellow) with shallow tissue penetration ability that does require invasive fiber-optic probes to deliver visible light into organs and animal tissues. This often results in a series of side effects, such as tissue damage and unwanted inflammation. Fortunately, the emerging wireless optogenetic tools that can respond to deep-tissue-penetrating near-infrared (NIR) light have attracted increasing attention due to their much-reduced damage to living organisms. There are mainly two types of NIR-activatable optogenetic tools: one uses lanthanide-doped upconversion nanoparticles to transduce NIR light to visible light to modulate classical opsin-expressing neurons; the other type couples with an NIR absorber to convert NIR light to heat to activate thermosensitive proteins. These NIR-activatable optogenetic tools enable low-invasive 'remote control' activation and inhibition of cellular signaling pathways. This approach has great potential to help create more innovative therapies for diseases like cancer, diabetes, and neuronal disorders in the near future. Therefore, this review article summarizes the recent advances on design strategies and synthetic methods of NIR-activatable nanomaterials for wireless optogenetic applications.
关键词： nanomaterials,near infrared,optogenetics,photothermal,upconversion
更新于2025-09-23 15:23:52
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Melanopsin for precise optogenetic activation of astrocyte-neuron networks
摘要： Optogenetics has been widely expanded to enhance or suppress neuronal activity and it has been recently applied to glial cells. Here, we have used a new approach based on selective expression of melanopsin, a G-protein-coupled photopigment, in astrocytes to trigger Ca2+ signaling. Using the genetically encoded Ca2+ indicator GCaMP6f and two-photon imaging, we show that melanopsin is both competent to stimulate robust IP3-dependent Ca2+ signals in astrocyte fine processes, and to evoke an ATP/Adenosine-dependent transient boost of hippocampal excitatory synaptic transmission. Additionally, under low-frequency light stimulation conditions, melanopsin-transfected astrocytes can trigger long-term synaptic changes. In vivo, melanopsin-astrocyte activation enhances episodic-like memory, suggesting melanopsin as an optical tool that could recapitulate the wide range of regulatory actions of astrocytes on neuronal networks in behaving animals. These results describe a novel approach using melanopsin as a precise trigger for astrocytes that mimics their endogenous G-protein signaling pathways, and present melanopsin as a valuable optical tool for neuron–glia studies.
关键词： neuron–glia interactions,synaptic plasticity,optogenetics,astrocytes,melanopsin
更新于2025-09-23 15:23:52
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Closed-loop functional optogenetic stimulation
摘要： Optogenetics has been used to orchestrate temporal- and tissue-specific control of neural tissues and offers a wealth of unique advantages for neuromuscular control. Here, we establish a closed-loop functional optogenetic stimulation (CL-FOS) system to control ankle joint position in murine models. Using the measurement of either joint angle or fascicle length as a feedback signal, we compare the controllability of CL-FOS to closed-loop functional electrical stimulation (CL-FES) and demonstrate significantly greater accuracy, lower rise times and lower overshoot percentages. We demonstrate orderly recruitment of motor units and reduced fatigue when performing cyclical movements with CL-FOS compared with CL-FES. We develop and investigate a 3-phase, photo-kinetic model to elucidate the underlying mechanisms for temporal variations in optogenetically activated neuromusculature during closed-loop control experiments. Methods and insights from this study lay the groundwork for the development of closed-loop optogenetic neuromuscular stimulation therapies and devices for peripheral limb control.
关键词： Functional stimulation,Photo-kinetic model,Motor units,Optogenetics,Neuromuscular control,Fatigue,Closed-loop control
更新于2025-09-23 15:23:52
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A wireless closed-loop system for optogenetic peripheral neuromodulation
摘要： The fast-growing field of bioelectronic medicine aims to develop engineered systems that can relieve clinical conditions by stimulating the peripheral nervous system. This type of technology relies largely on electrical stimulation to provide neuromodulation of organ function or pain. One example is sacral nerve stimulation to treat overactive bladder, urinary incontinence and interstitial cystitis (also known as bladder pain syndrome). Conventional, continuous stimulation protocols, however, can cause discomfort and pain, particularly when treating symptoms that can be intermittent (for example, sudden urinary urgency). Direct physical coupling of electrodes to the nerve can lead to injury and inflammation. Furthermore, typical therapeutic stimulators target large nerve bundles that innervate multiple structures, resulting in a lack of organ specificity. Here we introduce a miniaturized bio-optoelectronic implant that avoids these limitations by using (1) an optical stimulation interface that exploits microscale inorganic light-emitting diodes to activate opsins; (2) a soft, high-precision biophysical sensor system that allows continuous measurements of organ function; and (3) a control module and data analytics approach that enables coordinated, closed-loop operation of the system to eliminate pathological behaviours as they occur in real-time. In the example reported here, a soft strain gauge yields real-time information on bladder function in a rat model. Data algorithms identify pathological behaviour, and automated, closed-loop optogenetic neuromodulation of bladder sensory afferents normalizes bladder function. This all-optical scheme for neuromodulation offers chronic stability and the potential to stimulate specific cell types.
关键词： optogenetics,closed-loop system,bladder function,wireless implant,bioelectronic medicine,neuromodulation
更新于2025-09-23 15:23:52
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New light on neurotransmitter-gated receptors: Optical approaches for controlling physiological function
摘要： Neurotransmitter-gated receptors contribute to synaptic transmission and modulation in many ways. Considering glutamate receptors as an example, it becomes clear that these receptor families are highly diverse and that it is experimentally challenging to disentangle the different functional contributions of closely related receptor subtypes. Pharmacological and genetic methods are now complemented by optogenetic approaches, which allow for controlling receptor signaling with light. Using glutamate receptors as an example, I summarize how tethered photoswitchable ligands can be used to control individual receptor subtypes with high spatial and temporal precision, and in specific cells. These, and similarly exciting approaches, offer new possibilities for probing the function of individual receptors in the nervous system.
关键词： optogenetics,ligand-gated ion channels,optopharmacology,G protein-coupled receptors,glutamate receptors
更新于2025-09-23 15:23:52
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In vivo Optogenetic Approach to Study Neuron-Oligodendroglia Interactions in Mouse Pups
摘要： Optogenetic and pharmacogenetic techniques have been effective to analyze the role of neuronal activity in controlling oligodendroglia lineage cells in behaving juvenile and adult mice. This kind of studies is also of high interest during early postnatal development since important changes in oligodendroglia dynamics occur during the first two PN weeks. Yet, neuronal manipulation is difficult to implement at an early age because high-level, specific protein expression is less reliable in neonatal mice. Here, we describe a protocol allowing for an optogenetic stimulation of neurons in awake mouse pups with the purpose of investigating the effect of neuronal activity on oligodendroglia dynamics during early PN stages. Since GABAergic interneurons contact oligodendrocyte precursor cells (OPCs) through bona fide synapses and maintain a close relationship with these progenitors during cortical development, we used this relevant example of neuron-oligodendroglia interaction to implement a proof-of-principle optogenetic approach. First, we tested Nkx2.1-Cre and Parvalbumin (PV)-Cre lines to drive the expression of the photosensitive ion channel channelrhodopsin-2 (ChR2) in subpopulations of interneurons at different developmental stages. By using patch-clamp recordings and photostimulation of ChR2-positive interneurons in acute somatosensory cortical slices, we analyzed the level of functional expression of ChR2 in these neurons. We found that ChR2 expression was insufficient in PV-Cre mouse at PN day 10 (PN10) and that this channel needs to be expressed from embryonic stages (as in the Nkx2.1-Cre line) to allow for a reliable photoactivation in mouse pups. Then, we implemented a stereotaxic surgery to place a mini-optic fiber at the cortical surface in order to photostimulate ChR2-positive interneurons at PN10. In vivo field potentials were recorded in Layer V to verify that photostimulation reaches deep cortical layers. Finally, we analyzed the effect of the photostimulation on the layer V oligodendroglia population by conventional immunostainings. Neither the total density nor a proliferative fraction of OPCs were affected by increasing interneuron activity in vivo, complementing previous findings showing the lack of effect of GABAergic synaptic activity on OPC proliferation. The methodology described here should provide a framework for future investigation of the role of early cellular interactions during PN brain maturation.
关键词： optogenetics,developing brain,proliferation,oligodendrocyte precursor cell,GABAergic interneuron,somatosensory cortex
更新于2025-09-23 15:23:52