Label-free photoacoustic computed tomography of visually evoked responses in the primary visual cortex and four subcortical retinorecipient nuclei of anesthetized mice.

Significance: Many techniques exist for screening retinal phenotypes in mouse models in vision research, but significant challenges remain for efficiently probing higher visual centers of the brain. Photoacoustic computed tomography (PACT), with optical sensitivity to hemodynamic response (HR) in brain and ultrasound resolution, provides unique advantages in comprehensively assessing higher visual function in the mouse brain. Aim: We aim to examine the reliability of PACT in the functional phenotyping of mouse models for vision research. Approach: A PACT-ultrasound (US) parallel imaging system was established with a one-dimensional (1D) US transducer array and a tunable laser. Imaging was performed at three coronal planes of the brain, covering the primary visual cortex and the four subcortical nuclei, including the superior colliculus, the dorsal lateral geniculate nucleus, the suprachiasmatic nucleus, and the olivary pretectal nucleus. The visual-evoked HR was isolated from background signals using an impulse-based data processing protocol. rd1 mice with rod/cone degeneration, melanopsin-knockout (mel-KO) mice with photoreceptive ganglion cells that lack intrinsic photosensitivity, and wild-type mice as controls were imaged. The quantitative characteristics of the visual-evoked HR were compared. Results: Quantitative analysis of the HRs shows significant differences among the three mouse strains: (1) rd1 mice showed both smaller and slower responses compared with wild type ( n = 10,10 , p < 0.01 ) and (2) mel-KO mice had lower amplitude but not significantly delayed photoresponses than wild-type mice ( n = 10,10 , p < 0.01 ). These results agree with the known visual deficits of the mouse strains. Conclusions: PACT demonstrated sufficient sensitivity to detecting post-retinal functional deficits.

Photobiomodulation on isolated mitochondria at 810 nm: first results on the efficiency of the energy conversion process.

In this paper the photobiomodulation on isolated mitochondria of bovine liver is studied as a thermodynamic process of conversion of energy. This analysis is conducted by considering a particular set-up for the photobiomodulation experiments of interest. It allows, in particular, the computation of the electromagnetic field and the related energetic quantities in the stimulated organelles. The measurements of the excess of biochemical power density produced by the illuminated mitochondria are performed at regular time intervals after the experiments. The calculations and the measurements finally allow us to obtain the first results on the efficiency of the process of conversion of electromagnetic energy into excess of biochemical energy released by the isolated organelles.

Effect of photostimulation through red LED light radiation on natural fermentation of table olives: An innovative case study with Negrinha the Freixo variety.

In this study, for the first time, red LED light radiation was applied to the fermentation process of table olives using the Negrinha de Freixo variety. Photostimulation using LED light emission (630 ± 10 nm) is proposed to shorten and speed up this stage and reduce time to market. Several physical-chemical characteristics and microorganisms (total microbial count of mesophilic aerobic, molds, yeasts, and lactic acid bacteria) and their sequence during fermentation were monitored. The fermentation occurred for 122 days, with two irradiation periods for red LED light. The nutritional composition and sensory analysis were performed at the end of the process. Fermentation under red LED light increased the viable yeast and lactic acid bacteria (LAB) cell counts and decreased the total phenolics in olives. Even though significant differences were observed in some color parameters, the hue values were of the same order of magnitude and similar for both samples. Furthermore, the red LED light did not play a relevant change in the texture profile, preventing the softening of the fruit pulp. Similarly, LED light did not modify the existing type of microflora but increased species abundance, resulting in desirable properties and activities. The species identified were yeasts - Candida boidinii, Pichia membranifaciens, and Saccharomyces cerevisiae, and bacteria - Lactobacillus plantarum and Leuconostoc mesenteroides, being the fermentative process dominated by S. cerevisiae and L. plantarum. At the end of fermentation (122 days), the irradiated olives showed less bitterness and acidity, higher hardness, and lower negative sensory attributes than non-irradiated. Thus, the results of this study indicate that red LED light application can be an innovative technology for table olives production.

Ultra-Low-Dose UV-C Photo-stimulation Promotes Neural Stem Cells Differentiation via Presenilin 1 Mediated Notch and ß-Catenin Activation.

Light-based photo-stimulation has demonstrated promising effects on stem cell behavior, particularly in optimizing neurogenesis. However, the precise parameters for achieving optimal results, including the wavelengths, light intensity, radiating energy, and underlying mechanisms, remain incompletely understood. In this study, we focused on utilizing ultraviolet-C (UV-C) at a specific wavelength of 254 nm, with an ultra-low dose at intensity of 330 µW/cm2 and a total energy of 594 mJ/cm2 per day over a period of seven days, to stimulate the proliferation and differentiation of mouse neural stem cells (NSCs). The results revealed that the application of ultra-low-dose UV-C yielded the most significant effect in promoting differentiation when compared to mixed ultraviolet (UV) and ultraviolet-A (UV-A) radiation at equivalent exposure levels. The mechanism exploration elucidated the role of Presenilin 1 in mediating the activation of ß-catenin and Notch 1 by the UV-C treatment, both of which are key factors facilitating NSCs proliferation and differentiation. These findings introduce a novel approach employing ultra-low-dose UV-C for specifically enhancing NSC differentiation, as well as the underlying mechanism. It would contribute valuable insights into brain stimulation and neurogenesis modulation for various diseases, offering potential therapeutic avenues for further exploration.

Nanoactuator for Neuronal Optoporation.

Light-driven modulation of neuronal activity at high spatial-temporal resolution is becoming of high interest in neuroscience. In addition to optogenetics, nongenetic membrane-targeted nanomachines that alter the electrical state of the neuronal membranes are in demand. Here, we engineered and characterized a photoswitchable conjugated compound (BV-1) that spontaneously partitions into the neuronal membrane and undergoes a charge transfer upon light stimulation. The activity of primary neurons is not affected in the dark, whereas millisecond light pulses of cyan light induce a progressive decrease in membrane resistance and an increase in inward current matched to a progressive depolarization and action potential firing. We found that illumination of BV-1 induces oxidation of membrane phospholipids, which is necessary for the electrophysiological effects and is associated with decreased membrane tension and increased membrane fluidity. Time-resolved atomic force microscopy and molecular dynamics simulations performed on planar lipid bilayers revealed that the underlying mechanism is a light-driven formation of pore-like structures across the plasma membrane. Such a phenomenon decreases membrane resistance and increases permeability to monovalent cations, namely, Na+, mimicking the effects of antifungal polyenes. The same effect on membrane resistance was also observed in nonexcitable cells. When sustained light stimulations are applied, neuronal swelling and death occur. The light-controlled pore-forming properties of BV-1 allow performing "on-demand" light-induced membrane poration to rapidly shift from cell-attached to perforated whole-cell patch-clamp configuration. Administration of BV-1 to ex vivo retinal explants or in vivo primary visual cortex elicited neuronal firing in response to short trains of light stimuli, followed by activity silencing upon prolonged light stimulations. BV-1 represents a versatile molecular nanomachine whose properties can be exploited to induce either photostimulation or space-specific cell death, depending on the pattern and duration of light stimulation.

Fractal Phototherapy in Maximizing Retina and Brain Plasticity.

The neuroplasticity potential is reduced with aging and impairs during neurodegenerative diseases and brain and visual system injuries. This limits the brain's capacity to repair the structure and dynamics of its activity after lesions. Maximization of neuroplasticity is necessary to provide the maximal CNS response to therapeutic intervention and adaptive reorganization of neuronal networks in patients with degenerative pathology and traumatic injury to restore the functional activity of the brain and retina.Considering the fractal geometry and dynamics of the healthy brain and the loss of fractality in neurodegenerative pathology, we suggest that the application of self-similar visual signals with a fractal temporal structure in the stimulation therapy can reactivate the adaptive neuroplasticity and enhance the effectiveness of neurorehabilitation. This proposition was tested in the recent studies. Patients with glaucoma had a statistically significant positive effect of fractal photic therapy on light sensitivity and the perimetric MD index, which shows that methods of fractal stimulation can be a novel nonpharmacological approach to neuroprotective therapy and neurorehabilitation. In healthy rabbits, it was demonstrated that a long-term course of photostimulation with fractal signals does not harm the electroretinogram (ERG) and retina structure. Rabbits with modeled retinal atrophy showed better dynamics of the ERG restoration during daily stimulation therapy for a week in comparison with the controls. Positive changes in the retinal function can indirectly suggest the activation of its adaptive plasticity and the high potential of stimulation therapy with fractal visual stimuli in a nonpharmacological neurorehabilitation, which requires further study.

Contribution of optical resolution to the spatial precision of two-photon optogenetic photostimulation in vivo.

Significance: Two-photon optogenetics combines nonlinear excitation with noninvasive activation of neurons to enable the manipulation of neural circuits with a high degree of spatial precision. Combined with two-photon population calcium imaging, these approaches comprise a flexible platform for all-optical interrogation of neural circuits. However, a multitude of optical and biological factors dictate the exact precision of this approach in vivo, where it is most usefully applied. Aim: We aimed to assess how the optical point spread function (OPSF) contributes to the spatial precision of two-photon photostimulation in neurobiology. Approach: We altered the axial spread of the OPSF of the photostimulation beam using a spatial light modulator. Subsequently, calcium imaging was used to monitor the axial spatial precision of two-photon photostimulation of layer 2 neurons in the mouse neocortex. Results: We found that optical resolution is not always the limiting factor of the spatial precision of two-photon optogenetic photostimulation and, by doing so, reveal the key factors that must be improved to achieve maximal precision. Conclusions: Our results enable future work to focus on the optimal factors by providing key insight from controlled experiments in a manner not previously reported. This research can be applied to advance the state-of-the-art of all-optical interrogation, extending the toolkit for neuroscience research to achieve spatiotemporal precision at the crucial levels in which neural circuits operate.

Photobiomodulation CME Part I: Overview and Mechanism of Action.

Photobiomodulation (PBM), previously known as low-level laser light therapy, represents a non-invasive form of phototherapy that utilizes wavelengths in the red light (RL, 620-700 nm) portion of the visible light (VL, 400-700 nm) spectrum and the near-infrared (NIR, 700-1440 nm) spectrum. PBM is a promising and increasingly used therapy for the treatment of various dermatologic and non-dermatologic conditions. Photons from RL and NIR are absorbed by endogenous photoreceptors including mitochondrial cytochrome C oxidase (COX). Activation of COX leads to the following changes: modulation of mitochondrial adenosine triphosphate (ATP), generation of reactive oxygen species (ROS), and alterations in intracellular calcium levels. The associated modulation of ATP, ROS and calcium levels promotes the activation of various signaling pathways (e.g., insulin-like growth factors, phosphoinositide 3-kinase pathways), which contribute to downstream effects on cellular proliferation, migration and differentiation. Effective PBM therapy is dependent on treatment parameters (e.g., fluence, treatment duration and output power). PBM is generally well-tolerated and safe with erythema being the most common and self-limiting adverse cutaneous effect.

Photo-Controllable Ultralong Room-Temperature Phosphorescence: State of the Art.

In this concept, we showcase the upsurge in the studies of dynamic ultralong room-temperature phosphorescence (RTP) materials containing inorganic and/or organic components as versatile photo-responsive platforms. The goal is to provide a comprehensive analysis of photo-controllable RTP, and meanwhile delve into the underlying RTP properties of various classes of photochromic materials including metal-organic complexes, organic-inorganic co-crystals, purely organic small molecules and organic polymers. In particular, the design principles governing the integration of the photochromic and RTP moieties within a single material system, and the tuning of dynamic RTP in response to light are emphasized. As such, this concept sheds light on the challenges and opportunities of using these tunable RTP materials for potential applications in optoelectronics, particularly highlighting their use of reversible information encryption, erasable light printing and rewritable smart paper.

Holographic stimulation of opposing amygdala ensembles bidirectionally modulates valence-specific behavior via mutual inhibition.

The basolateral amygdala (BLA) is an evolutionarily conserved brain region, well known for valence processing. Despite this central role, the relationship between activity of BLA neuronal ensembles in response to appetitive and aversive stimuli and the subsequent expression of valence-specific behavior has remained elusive. Here, we leverage two-photon calcium imaging combined with single-cell holographic photostimulation through an endoscopic lens to demonstrate a direct causal role for opposing ensembles of BLA neurons in the control of oppositely valenced behavior in mice. We report that targeted photostimulation of either appetitive or aversive BLA ensembles results in mutual inhibition and shifts behavioral responses to promote consumption of an aversive tastant or reduce consumption of an appetitive tastant, respectively. Here, we identify that neuronal encoding of valence in the BLA is graded and relies on the relative proportion of individual BLA neurons recruited in a stable appetitive or quinine ensemble.

Photostimulation of lymphatic clearance of ß-amyloid from mouse brain: a new strategy for the therapy of Alzheimer's disease.

Alzheimer's disease (AD) is an age-related neurodegenerative disorder that poses a significant burden on socio-economic and healthcare systems worldwide. However, the currently available therapy of AD is limited, and new strategies are needed to enhance the clearance of ß-amyloid (Aß) protein and improve cognitive function. Photobiomodulation (PBM) is a non-invasive and effective therapeutic method that has shown promise in treating various brain diseases. Here, we demonstrate that 1267-nm PBM significantly alleviates cognitive decline in the 5xFAD mouse model of AD and is safe as it does not induce a significant increase in cortical temperature. Moreover, with the combination of 3D tissue optical clearing imaging and automatic brain region segmentation, we show that PBM-mediated reductions of Aß plaques in different subregions of prefrontal cortex and the hippocampus are different. The PBM-induced lymphatic clearance of Aß from the brain is associated with improvement of memory and cognitive functions in 5xFAD mice. Our results suggest that the modulation of meningeal lymphatic vessels (MLVs) should play an important role in promoting Aß clearance. Collectively, this pilot study demonstrates that PBM can safely accelerate lymphatic clearance of Aß from the brain of 5xFAD mice, promoting improvement of neurocognitive status of AD animals suggesting that PBM can be an effective and bedside therapy for AD.

Mechanisms of Photostimulation of Brain's Waste Disposal System: The Role of Singlet Oxygen.

There is strong evidence that augmentation of the brain's waste disposal system via stimulation of the meningeal lymphatics might be a promising therapeutic target for preventing neurological diseases. In our previous studies, we demonstrated activation of the brain's waste disposal system using transcranial photostimulation (PS) with a laser 1267 nm, which stimulates the direct generation of singlet oxygen in the brain tissues. Here we investigate the mechanisms underlying this phenomenon. Our results clearly demonstrate that PS-mediated stimulation of the brain's waste disposal system is accompanied by activation of lymphatic contractility associated with subsequent intracellular production of the reactive oxygen species and the nitric oxide underlying lymphatic relaxation. Thus, PS stimulates the brain's waste disposal system by influencing the mechanisms of regulation of lymphatic pumping.

Photo-Chemical Stimulation of Neurons with Organic Semiconductors.

Recent advances in light-responsive materials enabled the development of devices that can wirelessly activate tissue with light. Here it is shown that solution-processed organic heterojunctions can stimulate the activity of primary neurons at low intensities of light via photochemical reactions. The p-type semiconducting polymer PDCBT and the n-type semiconducting small molecule ITIC (a non-fullerene acceptor) are coated on glass supports, forming a p-n junction with high photosensitivity. Patch clamp measurements show that low-intensity white light is converted into a cue that triggers action potentials in primary cortical neurons. The study shows that neat organic semiconducting p-n bilayers can exchange photogenerated charges with oxygen and other chemical compounds in cell culture conditions. Through several controlled experimental conditions, photo-capacitive, photo-thermal, and direct hydrogen peroxide effects on neural function are excluded, with photochemical delivery being the possible mechanism. The profound advantages of low-intensity photo-chemical intervention with neuron electrophysiology pave the way for developing wireless light-based therapy based on emerging organic semiconductors.

Generation of green electricity from sludge using photo-stimulated bacterial consortium as a sustainable technology.

Microbial fuel cell (MFC) is a bio-electrical energy generator that uses respiring microbes to transform organic matter present in sludge into electrical energy. The primary goal of this work was to introduce a new approach to the green electricity generation technology. In this context a total of 6 bacterial isolates were recovered from sludge samples collected from El-Sheikh Zayed water purification plant, Egypt, and screened for their electrogenic potential. The most promising isolates were identified according to 16S rRNA sequencing as Escherichia coli and Enterobacter cloacae, promising results were achieved on using them in consortium at optimized values of pH (7.5), temperature (30°C) and substrate (glucose/pyruvate 1%). Low level red laser (λ = 632.8nm, 8mW) was utilized to promote the electrogenic efficiency of the bacterial consortium, maximum growth was attained at 210 sec exposure interval. In an application of adding standard inoculum (107 cfu/mL) of the photo-stimulated bacterial consortium to sludge based MFC a significant increase in the output potential difference values were recorded, the electricity generation was maintained by regular supply of external substrate. These results demonstrate the future development of the dual role of MFCs in renewable energy production and sludge recycling.

Phototherapy of Alzheimer's Disease: Photostimulation of Brain Lymphatics during Sleep: A Systematic Review.

The global number of people with Alzheimer's disease (AD) doubles every 5 years. It has been established that unless an effective treatment for AD is found, the incidence of AD will triple by 2060. However, pharmacological therapies for AD have failed to show effectiveness and safety. Therefore, the search for alternative methods for treating AD is an urgent problem in medicine. The lymphatic drainage and removal system of the brain (LDRSB) plays an important role in resistance to the progression of AD. The development of methods for augmentation of the LDRSB functions may contribute to progress in AD therapy. Photobiomodulation (PBM) is considered to be a non-pharmacological and safe approach for AD therapy. Here, we highlight the most recent and relevant studies of PBM for AD. We focus on emerging evidence that indicates the potential benefits of PBM during sleep for modulation of natural activation of the LDRSB at nighttime, providing effective removal of metabolites, including amyloid-ß, from the brain, leading to reduced progression of AD. Our review creates a new niche in the therapy of brain diseases during sleep and sheds light on the development of smart sleep technologies for neurodegenerative diseases.

MnO2 Nanoflower Integrated Optoelectronic Biointerfaces for Photostimulation of Neurons.

Optoelectronic biointerfaces have gained significant interest for wireless and electrical control of neurons. Three-dimentional (3D) pseudocapacitive nanomaterials with large surface areas and interconnected porous structures have great potential for optoelectronic biointerfaces that can fulfill the requirement of high electrode-electrolyte capacitance to effectively transduce light into stimulating ionic currents. In this study, the integration of 3D manganese dioxide (MnO2 ) nanoflowers into flexible optoelectronic biointerfaces for safe and efficient photostimulation of neurons is demonstrated. MnO2 nanoflowers are grown via chemical bath deposition on the return electrode, which has a MnO2 seed layer deposited via cyclic voltammetry. They facilitate a high interfacial capacitance (larger than 10 mF cm-2 ) and photogenerated charge density (over 20 µC cm-2 ) under low light intensity (1 mW mm-2 ). MnO2 nanoflowers induce safe capacitive currents with reversible Faradaic reactions and do not cause any toxicity on hippocampal neurons in vitro, making them a promising material for biointerfacing with electrogenic cells. Patch-clamp electrophysiology is recorded in the whole-cell configuration of hippocampal neurons, and the optoelectronic biointerfaces trigger repetitive and rapid firing of action potentials in response to light pulse trains. This study points out the potential of electrochemically-deposited 3D pseudocapacitive nanomaterials as a robust building block for optoelectronic control of neurons.

Store-Operated Ca2+ Channels Contribute to the Generation of Ca2+ Waves in Interdental Cells in the Cochleae.

Cochlear calcium (Ca2+) waves are vital regulators of the cochlear development and establishment of hearing function. Inner supporting cells are believed to be the main region generating Ca2+ waves that work as internal stimuli to coordinate the development of hair cells and the mapping of neurons in the cochlea. However, Ca2+ waves in interdental cells (IDCs) that connect to inner supporting cells and spiral ganglion neurons are rarely observed and poorly understood. Herein, we reported the mechanism of IDC Ca2+ wave formation and propagation by developing a single-cell Ca2+ excitation technology, which can easily be accomplished using a two-photon microscope for simultaneous microscopy and femtosecond laser Ca2+ excitation in any target individual cell in fresh cochlear tissues. We demonstrated that the store-operated Ca2+ channels in IDCs are responsible for Ca2+ wave formation in these cells. The specific architecture of the IDCs determines the propagation of Ca2+ waves. Our results provide the mechanism of Ca2+ formation in IDCs and a controllable, precise, and noninvasive technology to excite local Ca2+ waves in the cochlea, with good potential for research on cochlear Ca2+ and hearing functions.

Features of phototropic response of zooplankton to paired photostimulation under adverse environmental conditions.

Our previous studies showed that the change in the plankton response to light could be an indicator of environmental pollution. This study experimentally reveals that the response of Daphnia magna Straus and Daphnia pulex plankton ensembles to photostimulation depends on the intensity of the attracting light. This makes it difficult to identify the occurrence and change of pollutant concentration. The large variability in the magnitude of the behavioral response is caused by the nonlinear response of plankton ensembles to the intensity of the attractor stimulus. As the intensity of the photostimulation increases, the variability of the phototropic response passes through increase, decrease, and relative stabilization phases. The paper proposes a modification of the photostimulation method-paired photostimulation involving successive exposure to two photostimuli of increasing intensity. The first stimulus stabilizes the behavioral response, while the increase in response to the second stimulus makes it possible to more accurately assess the responsiveness of the plankton ensemble. The paper studies the sensitivity of the method of paired stimulation of the behavioral response of different types of freshwater plankton ensembles: Daphnia magna Straus, Daphnia pulex to the effects of pollutants (potassium bichromate, microplastic). The study demonstrates good reliability and increased sensitivity of this method of detecting changes in environmental toxicity compared to single photostimulation or traditional bioindication through the survival rate of test organisms.

The Involvement of Photobiology in Contemporary Dentistry-A Narrative Review.

Light is an emerging treatment approach that is being used to treat many diseases and conditions such as pain, inflammation, and wound healing. The light used in dental therapy generally lies in visible and invisible spectral regions. Despite many positive results in the treatment of different conditions, this therapy still faces some skepticism, which has prevented its widespread adoption in clinics. The main reason for this skepticism is the lack of comprehensive information about the molecular, cellular, and tissular mechanisms of action, which underpin the positive effects of phototherapy. However, there is currently promising evidence in support of the use of light therapy across a spectrum of oral hard and soft tissues, as well as in a variety of important dental subspecialties, such as endodontics, periodontics, orthodontics, and maxillofacial surgery. The merging of diagnostic and therapeutic light procedures is also seen as a promising area for future expansion. In the next decade, several light technologies are foreseen as becoming integral parts of modern dentistry practice.

Investigating the Modulation of the VTA Neurons in Nicotine-Exposed Pups during Early Maturation Using Optogenetics.

Advancing the understanding of the relationship between perinatal nicotine addiction and the reward mechanism of the brain is crucial for uncovering and implementing new treatments for addiction control and prevention. The mesolimbic pathway of the brain, also known as the reward pathway, consists of two main areas that regulate dopamine (DA) and addiction-related behaviors. The ventral tegmental area (VTA) releases DA when stimulated, causing the propagation of neuronal firing along the pathway. This ends in the release of DA into the extracellular space of the nucleus accumbens (NAc), which is directly modulated by the uptake of DA. Much research has been conducted on the effects of nicotine addiction, but little research has been conducted concerning nicotine addiction and the mesolimbic pathway regarding maturation due to the small brain size. In this study, we apply our novel microstimulation experimental system to rat pups that have been perinatally exposed to nicotine. By using our self-fabricated photo-stimulation (PS) device, we can stimulate the VTA and collect dialysate, which is then used to estimate DA released into the NAc. The proposed platform has demonstrated the potential to monitor neural pathways as the pups mature.