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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-β, 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. RSF RF Governmental Academic leadership program Priority 2030 proposed by the First Moscow State Medical University of the Ministry of Health of the Russian Federation (Sechenov University)

Optoelectronic systems can exert precise control over targeted neurons and pathways throughout the brain in untethered animals, but similar technologies for the spinal cord are not well established. In the present study, we describe a system for ultrafast, wireless, closed-loop manipulation of targeted neurons and pathways across the entire dorsoventral spinal cord in untethered mice. We developed a soft stretchable carrier, integrating microscale light-emitting diodes (micro-LEDs), that conforms to the dura mater of the spinal cord. A coating of silicone-phosphor matrix over the micro-LEDs provides mechanical protection and light conversion for compatibility with a large library of opsins. A lightweight, head-mounted, wireless platform powers the micro-LEDs and performs low-latency, on-chip processing of sensed physiological signals to control photostimulation in a closed loop. We use the device to reveal the role of various neuronal subtypes, sensory pathways and supraspinal projections in the control of locomotion in healthy and spinal-cord injured mice., Optogenetics is applied to the entire mouse spinal cord.

It is very important to maintain normal levels of risk avoidance in daily life. We found that DISC1-NTM mice, which are a model for mental disorders, had a phenotype marked by a risk-avoidance impairment as measured in an open-field test (OFT). We used optogenetic methods to modulate glutamatergic neurons in the basolateral amygdala (BLA) in an attempt to rescue this risk-avoidance impairment. We found that photostimulation of BLA neurons at 20 Hz modified DISC1-NTM mouse behavior from low risk avoidance to high risk avoidance. We observed following photostimulation that, compared to controls, the number of entries to the center of the open field was lower and less time was spent in the central area. We also found that the time spent immobile was higher during photostimulation compared with WT mice. We also used a lower photostimulation frequency of 5 Hz, which activated BLA glutamatergic neurons and rescued the risk-avoidance impairment in DISC1-NTM mice. Our findings confirm that the BLA participates in diverse risk-avoidance behavior. Our results are also a reminder that differences in neuronal firing patterns within the same pathway may lead to different physiological functions.

Исследование было произведено на 60 белых крысах породы, с моделированием операционной раны. Крысы были разделены на 5 групп по 6 крыс в каждой. 1 группа - контрольная, крысам из этой группы производили разрез на боковой стенке, брюшной стенке с последующим естественным заживлением в течении 10 дней; 2 группа - разрез с последующим применением хитозановой мази; 3 группа - на рану воздействовали фотостимуляцией, обработанной метиленовым синим; 4 группа - физические нагрузки в постоперационном периоде на беговой дорожке 30 минут; 5 группа - комплексное применение хитозана, фотостимуляции и физических нагрузок. Заживление ран фиксировали определением площади, производили фотофиксацию раны и прибегали к гистологическим исследованиям кожи и внутренних органов. Полученные результаты: лучшее заживление раны по данным планиметрии и гистологических исследований достоверно отмечено в 5 группе при комплексном лечении операционной раны. Выводы: реабилитационный комплекс при больших операционных ранах должен включать ранее местное воздействие физиотерапевтических процедур и физических нагрузок., The study was carried out on 60 white Wistar rats, simulating a surgical wound. The rats were divided into 5 groups of 6 rats each. Group 1 - control, rats from this group made an incision on the side wall, abdominal wall, followed by natural healing within 10 days; Group 2 - an incision followed by the use of chitosan ointment; Group 3 - the wound was exposed to photostimulation treated with methylene blue; Group 4 - physical activity in the postoperative period on a treadmill for 30 minutes; Group 5 - complex application of chitosan, photostimulation and physical activity. Wound healing was recorded by determining the area, photo fixation of the wound was performed, and histological examinations of the skin and internal organs were performed. Obtained results: The best wound healing according to planimetry and histological studies was reliably noted in group 5 with the complex treatment of the surgical wound. Conclusions: The rehabilitation complex for large surgical wounds should include previously local effects of physiotherapeutic procedures and physical activity., Изилдөө жумушу учун лабораториялык 60 ак Wistar келемиштери колдонулан. Келемиштер 6 келемиштен, 5 группага бөлүнгөн. 1группа - контролдук, 10 күндүн ичинде табигый айыктыруу; 2 группа - айыктырууда хитозан майы колдонулган; 3 группа - жараат фотостимуляцияга дуушар болгон; 4 группа -30 мүнөт бою операциядан кийинки мезгилде физикалык активдүүлүк; 5 группа - хитозанды, фотостимуляция жана физикалык активдүүлүк. Жараатты айыктыруу аймакты аныктоо менен бекитилип, жараатты сүрөткө тартып, терини жана ички органдарды гистологиялык изилдөө жургузулгөөн. Натыйжалар: Планиметрия жана гистологиялык изилдөөлөр боюнча жарааттын жакшы айыгышы, хирургиялык жараатты комплекстүү дарылоодо 5 группада белгиленди. Корутундулар: хирургиялык жарааттарды калыбына келтирүү комплекси, биринчи орунда физиотерапиянын жана физикалык активдүүлүк менен таасирлениши керек., Вестник Кыргызcкого национального аграрного университета, Выпуск 1 (64) 2023, Pages 102-107

The task is to identify differences in phase synchronization between the intermittent photic stimulation and a response of the brain of patients with arterial hypertension and manifestations of moderate cognitive impairment and without such manifestations. To solve the task we used the recurrence based phase synchronization index, the ratio of instantaneous frequencies, the duration and the phase synchronization index obtained after the synchrosqueezed wavelet transform of the EEG patterns and the light time series. We have shown that moderate cognitive impairment correlates with a greater degree of phase synchronization. This is manifested in an increase in the index and duration of phase synchronization between intermittent photostimulation and bioelectric activity of the brain, as well as with a shift in this activity to a lower frequency range compared to the excitation frequency. The results can be used for clinical assessment of the degree of moderate cognitive impairment of vascular origin.

Introduction: Adipose-derived stem cells (ASCs) show some membrane markers that enable cell identification by flow cytometry. One of them which is essential during the angiogenesis process is CD105 (Endoglin). This is very important for various pathologies where it is required angiogenesis to regenerate tissues or organs affected by various acquired or congenital noxae. To determine the phenotypic expression, CD105 angiogenesis factor, of ASCs obtain Objective: ed by Selective Tissue Engineering Photostimulation (STEP ) with infrared light of 1210 nm compared to those obtained by TM Gold Standard Suction assisted lipectomy/conventional liposuction technique (SAL). ASCs obtained by Results: STEP™ technique with 1210 nm laser were found to be highly viable (> 97%) and showed increased CD105 expression (90%) and only

Purpose. To study the possible effect of protective red light filter glasses as a method of preventing retinopathy of prematurity, based on the phenomenon of preconditioning photostimulation. Material and methods. For this study, we selected 20 children (40 eyes) from 26.5 to 36 weeks of gestational age and a birth weight of 650 to 2650 grams. All children were divided into 2 groups – the main and control groups of 10 children (20 eyes) each. Results. In the main group of the study, with the use of protective red light filter glasses, the best indicators of the electroretinogram were noted. Conclusions. The use of glasses with red protective light filters-as a method based on the phenomenon of preconditioning photostimulation, is a simple and affordable method of preventing retinopathy of prematurity, which reduces the need for surgical laser treatment and the number of adverse outcomes of this disease. Key words: retinopathy of prematurity, methods of prevention of retinopathy of prematurity.

The frontal lobes make a significant contribution to the formation of individual personality traits, in connection with which it is important to identify the links between the parameters of the bioelectric activity of the frontal cortex and the indicators of psychological tests. The aim of this work was to study the relationship between the indicators of extraversion and neuroticism of the subjects and the parameters of their EEG. For the first time, differences in these relationships were found at rest and during standard functional tests, without the use of additional specialized loads. The study involved healthy subjects of both sexes, average age 19.3 years; all subjects are right-handed. To identify the level of extraversion and neuroticism, the standard Eysenck test (option B) was used. The EEG was recorded using the bipolar derivation method. 19 electrodes were exposed in accordance with the international Jasper system 1020%. EEG was recorded at rest with eyes closed and during functional tests: eye opening, hyperventilation, photostimulation. The correlation coefficients of the index and absolute power of the EEG with the level of extraversion and neuroticism were calculated both for the entire sample of subjects and for individual groups according to the level of extraversion and the level of neuroticism. For the entire sample of subjects, positive significant correlations of EEG power with the level of extraversion and negative with the level of neuroticism were revealed. In the groups of subjects with high, medium and low levels of extraversion and neuroticism, the differences in correlation relationships with EEG parameters are more pronounced. In these groups, these differences are more often manifested when performing functional tests than at rest with closed eyes.

Optoelectronic biointerfaces offer a wireless and nongenetic neurostimulation pathway with high spatiotemporal resolution. Fabrication of low-cost and flexible optoelectronic biointerfaces that have high photogenerated charge injection densities and clinically usable cell stimulation mechanism is critical for rendering this technology useful for ubiquitous biomedical applications. Here, supercapacitor technology is combined with flexible organic optoelectronics by integrating RuO2 into a donor–acceptor photovoltaic device architecture that facilitates efficient and safe photostimulation of neurons. Remarkably, high interfacial capacitance of RuO2 resulting from reversible redox reactions leads to more than an order-of-magnitude increase in the safe stimulation mechanism of capacitive charge transfer. The RuO2-enhanced photoelectrical response activates voltage-gated sodium channels of hippocampal neurons and elicits repetitive, low-light intensity, and high-success rate firing of action potentials. Double-layer capacitance together with RuO2-induced reversible faradaic reactions provide a safe stimulation pathway, which is verified via intracellular oxidative stress measurements. All-solution-processed RuO2-based biointerfaces are flexible, biocompatible, and robust under harsh aging conditions, showing great promise for building safe and highly light-sensitive next-generation neural interfaces.

Understanding circuit-level manipulations that affect the brain’s capacity for plasticity will inform the design of targeted interventions that enhance recovery after stroke. Following stroke, increased contralesional activity (e.g. use of the unaffected limb) can negatively influence recovery, but it is unknown which specific neural connections exert this influence, and to what extent increased contralesional activity affects systems- and molecular-level biomarkers of recovery. Here, we combine optogenetic photostimulation with optical intrinsic signal imaging to examine how contralesional excitatory activity affects cortical remodeling after stroke in mice. Following photothrombosis of left primary somatosensory forepaw (S1FP) cortex, mice either recovered spontaneously or received chronic optogenetic excitation of right S1FP over the course of 4 weeks. Contralesional excitation suppressed perilesional S1FP remapping and was associated with abnormal patterns of stimulus-evoked activity in the unaffected limb. This maneuver also prevented the restoration of resting-state functional connectivity (RSFC) within the S1FP network, RSFC in several networks functionally distinct from somatomotor regions, and resulted in persistent limb-use asymmetry. In stimulated mice, perilesional tissue exhibited transcriptional changes in several genes relevant for recovery. Our results suggest that contralesional excitation impedes local and global circuit reconnection through suppression of cortical activity and several neuroplasticity-related genes after stroke, and highlight the importance of site selection for targeted therapeutic interventions after focal ischemia.

Rhythmic light stimulation can alter the electrical activity of the human and animal brain. Moreover, the brain response to certain flicker frequencies significantly exceeds the responses to neighboring frequencies. This phenomenon is thought to be related with the effect of resonance, as evidenced by the coincidence of one of the maxima in the profile of the response to flashes with the frequency of the alpha rhythm. However, other frequencies that cause an increased response to flashes are not reflected in electroencephalogram (EEG) as dominant oscillations. The goal of this study was to reveal the relationship between local maxima in the profile of the responses to flashes of different frequencies and dominant brain oscillations recorded in electrocorticogram (ECoG) of rhesus monkeys without stimulation. The study was carried out on four male rhesus monkeys Macaca mulatta. In three animals, peak responses were elicited by flickers at 8 and 16 Hz, while one monkey showed the second peak in the 22–30 Hz range. The first maximum (8–10 Hz) in the profile of the response to rhythmic photostimulation coincided with the dominant rhythm recorded in the occipital and parietal regions at rest. The second maximum at 16 Hz coincided with the dominant ECoG rhythm in one of the primates when it was in the state of emotional arousal, which may account for the resonant origin of the increase in responses in this frequency range. The data obtained indicate that dominant brain rhythms, including latent rhythms revealed only by rhythmic photostimulation, can coincide in frequency in monkeys and humans. The mechanisms behind the selective sensitivity of neural networks to different frequencies of photostimulation are discussed.

In this paper, we propose a method for estimating the frequency modulation of EEGs based on Fourier filtering of the initial signal on a narrow frequency band, followed by calculation of the time taken to reach both maximum and minimum peak values of the reconstructed signal (peak-to-peak periods). The resulting sequences were processed using the Fourier transform. EEGs recorded from healthy volunteers during photostimulation were used as the objects of study. Overall, EEG responses with a frequency range of 7 to 9 Hz demonstrated a more pronounced phenomenon of frequency modulation for occipital leads than those with the frequency range of 13 to 15 Hz. There were almost no differences in power spectral indices that modulate EEGs. Two types of EEG frequency modulation were revealed in the studied frequency ranges; the first type is not related to frequencies and is characterized by either a high or low level of exposure, while the second type has a connection between the nature of the modulation and the “carrier” frequency of the signal.

Optogenetic tools such as channelrhodopsin-2 (ChR2) enable the manipulation and mapping of neural circuits. However, ChR2 variants selectively transported down a neuron’s long-range axonal projections for precise presynaptic activation remain lacking. As a result, ChR2 activation is often contaminated by the spurious activation of en passant fibers that compromise the accurate interpretation of functional effects. Here, we explored the engineering of a ChR2 variant specifically localized to presynaptic axon terminals. The metabotropic glutamate receptor 2 (mGluR2) C-terminal domain fused with a proteolytic motif and axon-targeting signal (mGluR2-PA tag) localized ChR2-YFP at axon terminals without disturbing normal transmission. mGluR2-PA-tagged ChR2 evoked transmitter release in distal projection areas enabling lower levels of photostimulation. Circuit connectivity mapping in vivo with the Spike Collision Test revealed that mGluR2-PA-tagged ChR2 is useful for identifying axonal projection with significant reduction in the polysynaptic excess noise. These results suggest that the mGluR2-PA tag helps actuate trafficking to the axon terminal, thereby providing abundant possibilities for optogenetic experiments., Hamada et al. engineer and utilise a channelrhodopsin-2 variant that is localized to presynaptic axon terminals. They demonstrate its use for circuitry mapping in vivo and thus provide a useful tool for future optogenetic experiments

The lateral hypothalamic area (LHA) plays a pivotal role in regulating consciousness transition, in which orexinergic neurons, GABAergic neurons, and melanin-concentrating hormone neurons are involved. Glutamatergic neurons have a large population in the LHA, but their anesthesia-related effect has not been explored. Here, we found that genetic ablation of LHA glutamatergic neurons shortened the induction time and prolonged the recovery time of isoflurane anesthesia in mice. In contrast, chemogenetic activation of LHA glutamatergic neurons increased the time to anesthesia and decreased the time to recovery. Optogenetic activation of LHA glutamatergic neurons during the maintenance of anesthesia reduced the burst suppression pattern of the electroencephalogram (EEG) and shifted EEG features to an arousal pattern. Photostimulation of LHA glutamatergic projections to the lateral habenula (LHb) also facilitated the emergence from anesthesia and the transition of anesthesia depth to a lighter level. Collectively, LHA glutamatergic neurons and their projections to the LHb regulate anesthetic potency and EEG features.

The cortex processes information through intricate circuitry and outputs to multiple brain areas by different sets of pyramidal cells (PCs). PCs form intra- and inter-laminar subnetworks, depending on PC projection subtypes. However, it remains unknown how individual PC subtypes are involved in cortical network activity and, thereby, in distinct brain functions. Here, we examined the effects of optogenetic manipulations of specific PC subtypes on network activity in the motor cortex. In layer V, the beta/gamma frequency band of oscillation was evoked by photostimulation, depending on PC subtypes. Our experimental and simulation results suggest that oscillatory activity is generated in reciprocal connections between pyramidal tract (PT) and fast-spiking cells. A similar frequency band was also observed in local field potentials during a pattern learning task. Manipulation of PT cell activity affected beta/gamma band power and learning. Our results suggest that PT cell-dependent oscillations play important roles in motor learning., Otsuka and Kawaguchi investigate how manipulation of pyramidal cell subtypes in the motor cortex affects cortical network activity. Their findings suggest that pyramidal cell type cell-dependent oscillatory activity play an important role in motor learning.

Introduction. Epilepsy is a common feature of mitochondrial disorders, including those associated with mutations in the POLG gene. Nevertheless, brain electrical activity features of POLG-related disorders in adult patients have not been adequately studied. Objective. To study the features and characteristics of the electroencephalography (EEG) pattern in adult patients with POLG-related disorders. Material and methods. Eight patients were examined: 7 with SANDO (Sensory Ataxic Neuropathy, Dysarthria, Ophthalmoparesis) syndrome, and 1 with MEMSA (Myoclonic Epilepsy Myopathy Sensory Ataxia) syndrome; median age was 32.5 years. All patients underwent routine EEG monitoring using a 19-channel electroencephalograph according to the generally accepted method. Results. Epileptic seizures were found in 3 patients, for 2 of them – as the first manifestation of the disease. In 6 patients, theta waves predominated in the occipital regions. Of those 6 patients, in 5 bilateral synchronous bursts of theta and delta wave groups were identified being more prominent in the frontocentral regions; 4 patients had transient non-lateralized delta activity in the occipital and parieto-occipital brain regions. In all patients, opening eyes led to the depression of rhythms and burst suppression. After photostimulation, in 2 cases bilateral synchronous bursts of delta and theta wave groups were recorded predominantly in frontal lobes. In 3 patients during hyperventilation an increase in delta activity in the occipital lobes and bilateral synchronous bursts of delta wave groups were observed. Epileptiform activity was recorded in 2 cases. Conclusion. In adult patients with POLG-related disorders, regardless of the clinical manifestation, typical EEG features include generalized background slowing, theta and delta bursts in occipital lobes with their suppression by opening eyes.

Targeted green light photostimulation during the last stage of broiler incubation increases expression of the somatotropic axis. The purpose of this study was to further shorten the in ovo green light photostimulation and determine the critical age for photostimulation in broilers embryos, as a future strategy for broiler incubation. Fertile broilers eggs (n = 420) were divided into 5 treatment groups. The first group was incubated under standard conditions (in the dark) as the negative control group. The second was incubated under intermittent monochromatic green light using light-emitting diode lamps with an intensity of 0.1 W/m2 at shell level from embryonic day (ED) 0 of incubation until hatch, as a positive control. The third, fourth, and fifth groups were incubated under intermittent monochromatic green light from ED 15, 16, and 18 of incubation, respectively, until hatch. All treatment groups showed elevated somatotropic axis expression compared with the negative control, with the group incubated under monochromatic green light from ED 18 until hatch showing results closest to the positive control. This suggests that broiler embryos can be exposed to in ovo green light photostimulation from a late stage of incubation (when transferring the eggs to the hatchery) and exhibit essentially the same outcome as obtained by photostimulation during the entire incubation period.

Short-term memory is associated with persistent neural activity that is maintained by positive feedback between neurons. To explore the neural circuit motifs that produce memory-related persistent activity, we measured coupling between functionally characterized motor cortex neurons in mice performing a memory-guided response task. Targeted two-photon photostimulation of small (

Introduction. It is known that there are typological features among healthy young people according to the level of autonomic tone. Accordingly, there are groups of sympatho-, normo- and vagotonics. Work has been carried out to study the influence of the initial level of autonomic tone on thereactions of the cardiovascular system in respiratory hypocapnia, pulsed ophthalmic photostimulation, in different phases of the biological cycle for women. However, there is no work on the analysis of changes in the wave structure of heart rate depending on the initial level of autonomic tone. Purpose. The aim was to determine the features of the wave structure of the heart rhythm during orthoprobe for healthy young men with different levels of tone of the autonomic nervous system at rest. Methods. Measurements were performed in conditions close to the main exchange. 117 healthy young men aged 18-23 years were examined in compliance with the requirements of bioethics. Three main spectral components were analyzed in the tRR spectrum: HF (0.15-0.4 Hz) LF (0.04-0.15Hz); VLF (0-0.04 Hz); TP (0-0.4 Hz). The amplitude of the largest peak of the tRR spectrogram in the frequency range 0.04-0.15 Hz (aLF) and its frequency (tLF) were calculated. Normalized median spectrograms of tRR oscillations were constructed.Results.A significant decrease in HF was observed in individuals of all three groups during orthoprobe. The median reactivity of reactivity was -67.3%, -77.5%, -77.9% for groups I, II and III, respectively. There were no differences between the groups due to the reactivity of this indicator. The reactivity of LF to changes in body position for sympathotonics was significantly different.The frequency of the maximum peak of the spectrogram in the range of low often resting heart rate did not differ between groups. This indicator probably decreased during orthoprobe in groups IIand III. It was found that the wave has two peaks in the vertical position in persons with different baseline levels of autonomic tone for vagotonics and normotonics in the frequency range from 0.04 to0.15 Hz. Originality. Differences in the reactivity of heart rate waves to orthoprobe for healthy young men with different baseline levels of autonomic tone were detected for the first time. Conclusions. The greatest differences in changes in the wave structure of the heart rhythm during orthoprobe for persons with different baseline levels of autonomic tone are manifested in therange of low heart rate. Spectrum reduction reactions in this range were predominant for sympathotonics. The reactions of increasing LF and the amplitude of the maximum peak of the spectrogram were predominant for normo- and parasympathotonics. It was found that the wave has two peaks in the vertical position in persons with different baseline levels of autonomic tone for vagotonics and normotonics in the frequency range from 0.04 to 0.15 Hz. Sympathotonics have one wave of orthopedic reactivity with maxima at 0.09 Hz in the low heart rate range. Normotonics have two waves of reactivity per orthoprobe with frequencies of 0.08Hz and 0.11 Hz. Parasympathotonics also have two waves with frequencies of 0.07 Hz and 0.09Hz. Prospects for further research include elucidation of the mechanisms of tRR wave formation depending on the level of vegetative tone under different conditions. Key words: wave structure of heart rhythm, vegetative tone, sympathotonics, normotonics, vagotonics.

It is well known that rhythmic light stimulation can alter the electrical activity of the human and animal brain. Moreover, the brain response to certain flicker frequencies significantly exceeds the responses to neighboring frequencies. This phenomenon is thought to be related with the effect of resonance, as evidenced by the coincidence of one of the maxima in the profile of the response to flashes with the frequency of the alpha rhythm. However, other frequencies that cause an increased response to flashes are not reflected in electroencephalogram (EEG) as dominant oscillations. The goal of this study was to reveal the relationship between local maxima in the profile of the responses to flashes of different frequencies and dominant brain oscillations recorded in electrocorticogram (ECoG) of rhesus monkeys without stimulation. The study was carried out on four male Macaca mulatta individuals. In three animals, peak responses were elicited by flickers at 8 and 16 Hz, while one monkey showed a second peak in the 22−30 Hz range. The first maximum (8−10 Hz) in the profile of the response to rhythmic photostimulation coincided with the dominant rhythm recorded in the occipital and parietal regions at rest. The second maximum at 16 Hz coincided with the dominant ECoG rhythm in one of the primates when it was in the state of emotional arousal, which may account for the resonant origin of the increase in responses in this frequency range. The data obtained indicate that dominant brain rhythms, including latent rhythms revealed only by rhythmic photostimulation, can coincide in frequency in monkeys and humans. Neuronal mechanisms of selective sensitivity of neural networks to different frequencies of photostimulation are discussed.

In recent publications, positive results have been reported with the use of glasses with red protective filters in prematurely born infants with low body weight, which were presumably associated with a decrease in the levels of illumination of the environment of the child. However, to date, it has not been proven that a decrease in the amount of light reaching the retina of the newborn affects the frequency and severity of retinopathy of prematurity (RP). The analysis of the literature on the therapeutic effect of various modes of red and near infrared radiation on the retina is presented, which allowed a different look at the protective mechanisms of glasses-filters in premature babies. It has been suggested and substantiated that the observed effect may relate to the phenomenon of pre-conditioning photostimulation, which reduces the risk of developing RP and reduces the severity of the disease due to the induction of adaptive plastic reactions in the retina.

The aim of this study is to highlight the favorable effect of photostimulation obtained in the methotrexate therapy on Walker 256 tumour. The method of selective tumour photostimulation follows the increase, in the malignant tissue, of the concentration of any specific substance for the neoplastic cell that can be administered "in bolus" for cytostatic treatment. This goal is achieved by exposing the tumour tissue to the optical field emitted by a specially designed equipment. On the other hand, in the case of chemotherapy, there are certain types of cytostatics that have a "positive photodynamic potential", thus, following the interaction between their molecules and the light radiation with the strictly determined parameters, free radicals are born that destroy the intracellular cytostatic fixation targets. This phenomenon is called the photodynamic activation of the cytostatic, the method is called Photostimulated Chemotherapy (PSChT), and the drug used in this study is Methotrexate (MTX).

Low-power and high-frequency bidirectional control of spatiotemporal patterns of neural spiking is one of the major challenges in optogenetics. A detailed theoretical analysis and optimization with ChR2-NpHR, ChR2(H134R)-eNpHR3.0, Chrimson-GtACR2 and also with prospective opsin pairs namely, Chronos-Jaws, Chronos-eNpHR3.0, CheRiff-Jaws and vf-Chrimson-GtACR2 has been presented. Biophysical circuit models of bidirectional optogenetic control in above opsin pairs expressing hippocampal neurons and fast-spiking neocortical interneurons have been formulated. The models include the important rebound effect of chloride ions and overlapping of absorption spectra. Blue light absorption by red-shifted opsins not only affects the photocurrent, but also its turn-off kinetics. Under continuous illumination, bidirectional control of spiking around 40 Hz in hippocampal neurons requires very low blue and orange light intensities of 0.014 mW/mm2 and 0.8 mW/mm2 with CheRiff-Jaws and 0.04 mW/mm2, and 0.02 mW/mm2 with Chrimson-GtACR2, respectively. Under optimal photostimulation and expression density, high-frequency limit of bidirectional control is 60 Hz and 100 Hz with ChR2-NpHR, 60 Hz and 20 Hz with ChR2(H134R)-eNpHR3.0, 90 Hz and 180 Hz with Chronos-Jaws, and 90 Hz and 250 Hz with Chronos-eNpHR3.0 in neurons and interneurons, respectively. Although, Chrimson-GtACR2 enables bidirectional control at very low-power, vf-Chrimson-GtACR2 provides control with reduced cross-talk. The theoretical analysis highlights the usefulness of computational methods to virtually optimize stimulation protocols for optogenetic tool combinations. The study is useful to generate neural codes with desired spatiotemporal resolution and to design optogenetic neuroprosthetic devices and circuits.

The opsin family of G-protein-coupled receptors are used as light detectors in animals. Opsin 5 (also known as neuropsin or OPN5) is a highly conserved opsin that is sensitive to visible violet light1,2. In mice, OPN5 is a known photoreceptor in the retina3 and skin4 but is also expressed in the hypothalamic preoptic area (POA)5. Here we describe a light-sensing pathway in which POA neurons that express Opn5 regulate thermogenesis in brown adipose tissue (BAT). We show that Opn5 is expressed in glutamatergic warm-sensing POA neurons that receive synaptic input from several thermoregulatory nuclei. We further show that Opn5 POA neurons project to BAT and decrease its activity under chemogenetic stimulation. Opn5-null mice show overactive BAT, increased body temperature, and exaggerated thermogenesis when cold-challenged. Moreover, violet photostimulation during cold exposure acutely suppresses BAT temperature in wild-type mice but not in Opn5-null mice. Direct measurements of intracellular cAMP ex vivo show that Opn5 POA neurons increase cAMP when stimulated with violet light. This analysis thus identifies a violet light-sensitive deep brain photoreceptor that normally suppresses BAT thermogenesis. Mice possess neurons in the preoptic area of the hypothalamus that are sensitive to violet light; these deep brain neurons sense light via OPN5 and regulate adaptive thermogenesis in brown fat.

AIM: To evaluate the efficacy and safety of subthreshold micropulse yellow laser (SMYL) in the treatment of chronic central serous chorioretinopathy (CCSC). METHODS: The medical records of 58 eyes of 58 patients with CCSC were reviewed. A 577-nm SMYL system was used for the treatment. Fundus fluorescein angiography was used as the primary method of identifying CCSC, and resolution of subretinal fluid (SRF) evaluated by optical coherence tomography (OCT) and fundus autofluorescence. Central macular thickness (CMT), central macular volume (CMV), total macular volume (TMV), subfoveal choroidal thickness (SFCT), subretinal fluid height (SRFH), and subfoveal fluid basement diameter values were measured by spectral domain-OCT (SD-OCT) for all eyes. RESULTS: The mean age of the patients was 42.4±9.9 (range: 20-72)y. The mean follow-up was 11.4±8.5 (range: 6-37)mo. Median BCVA at at the final follow up after treatment was statistically significant from the baseline. Complete SRF resolution was 12.1% of the eyes in the 1(st) month, 67.2% of the eyes in the 3(rd) month and 67.2% of the eyes in the last follow up. The initial median CMT, CMV, TMV, and SFCT values before treatment was significantly higher than 3(rd) month visit values (P

Mitochondria locate close to endoplasmic reticulum (ER) and cooperate with ER to encode intracellular calcium signaling for cell processes and functions. However, the calcium coupling between mitochondria and ER (mito-ER) remains elusive due to the difficulty of precise excitation of localized mito-ER calcium coupling with little interference to other organelles. To study the mito-ER calcium coupling dynamics, we report a noninvasive method of photostimulation by femtosecond laser to excite the mito-ER calcium coupling at single-mitochondrion level. We establish a microscopy and photostimulation system to simultaneously stimulate and observe single mitochondrion continuously in real time, by which a long-term mito-ER calcium coupling is observed after a single short flash of femtosecond-laser stimulation to a tubular structure of a target mitochondrion in a pre-selected live cell. Cytosolic calcium is involved in the mito-ER calcium coupling but the mitochondrial sodium calcium exchanger and the mito-ER distance contribute little to it. Single mito-ER calcium coupling exhibits different dynamics from it excited by biochemical drugs globally. This study provides a precise and noninvasive method to excite calcium dynamics at single organelle level for the study of mitochondria and mito-ER calcium coupling.

The lateral cortex of the inferior colliculus (LCIC) forms a nexus between diverse multisensory, motor, and neuromodulatory streams. Like other integration hubs, it contains repeated neurochemical motifs with distinct inputs: GABA-rich modules are innervated by somatosensory structures, while auditory inputs to the LCIC target the surrounding extramodular matrix. To investigate potential mechanisms of convergence between these input streams, we used laser photostimulation circuit mapping to interrogate local LCIC circuits in adult mice of both sexes and found that input patterns are highly dependent on cell type (GABAergic/non-GABAergic) and location (module/matrix). At the circuit level, these inputs yield a directional flow of local information, primarily from the matrix to the modules. Further, the two compartments were found to project to distinct targets in the midbrain and thalamus. These data show that, while connectional modularity in the LCIC gives rise to segregated input-output channels, local circuits provide the architecture for integration between these two streams. SIGNIFICANCE STATEMENT Modularity is a widespread motif across the brain involving the segregation of structures into discrete subregions based on dichotomies in neurochemical expression or connectivity. The inferior colliculus is one such modular structure, containing auditory-recipient matrix regions and GABA-rich modules that are innervated by somatosensory inputs. While modularity suggests segregation of processing streams, here we show that local circuits in the inferior colliculus connect the module and matrix regions, providing an avenue for integration of information across compartments.

Optogenetics is an innovative and fast-growing field of science combining the advances in molecular biology and laser technologies to monitor various biochemical processes in the cell and to control its activity using light. Therefore, this review is devoted to the implementation of the optogenetic approach to diagnosis and treatment of various socially sensitive diseases at the molecular and genetic level. Furthermore, the article considers different methods of delivery and incorporation of genetic constructs encoding transmembrane proteins. New fiber optic technologies used to develop implantable devices for generating and recording signals in excitable tissues are described. Besides, the most state-of-the-art and popular registration methods are considered in the review.

Graphene conductive properties have been long exploited in the field of organic photovoltaics and optoelectronics by the scientific community worldwide. We engineered and characterized a hybrid biointerface in which graphene is coupled with photosensitive polymers, and tested its ability to elicit lighttriggered neural activity modulation in primary neurons and blind retina explants. We designed such a graphene-based device by modifying a photoactive P3HT-based retinal interface, previously reported to rescue light sensitivity in blind rodents, with a CVD graphene layer replacing the conductive PEDOT:PSS layer to enhance charge separation. The new graphene-based device was characterized for its electrochemical features and for the ability to photostimulate primary neurons and blind retina explants, while preserving biocompatibility. Light-triggered responses, recorded by patch-clamp in vitro or MEA ex vivo, show a stronger light-transduction efficiency when the neurons are interfaced with the graphene-based device with respect to the PEDOT:PSS-based one. The possibility to ameliorate flexible photo-stimulating devices via the insertion of graphene, paves the way for potential biomedical applications of graphenebased neuronal interfaces in the context of retinal implants., Comment: 10 pages, 5 figures

Two-photon microscopy is widely used to investigate brain function across multiple spatial scales. However, measurements of neural activity are compromised by brain movement in behaving animals. Brain motion-induced artefacts are typically corrected using post-hoc processing of 2D images, but this approach is slow and does not correct for axial movements. Moreover, the deleterious effects of brain movement on high speed imaging of small regions of interest and photostimulation cannot be corrected post-hoc. To address this problem, we combined random access 3D laser scanning using an acousto-optic lens and rapid closed-loop FPGA processing to track 3D brain movement and correct motion artifacts in real-time at up to 1 kHz. Our recordings from synapses, dendrites and large neuronal populations in behaving mice and zebrafish demonstrate real-time movement corrected 3D two-photon imaging with sub-micrometer precision., Editor summary: Real-time 3D movement correction by tracking a fluorescent bead in the field of view enables functional imaging with 3D two-photon random access microscopy in behaving mice and zebrafish.

The dynamics of the photic driving reaction was studied in subjects with panic attacks, using wavelet and recurrence analyses of electroencephalographic (EEG) patterns. Quantitative measures of the driving reaction to the given frequency were estimated from the increase in the energy of the wavelet spectrum during photostimulation, the coefficient of photic driving, and parameters of a joint recurrence plot of the light stimulus and EEG pattern (the rate and time of recurrence of the EEG trajectory into the vicinity of a previous point). The parameters were determined before and after non-drug therapy, which included activation and training of artificial stable functional connections (ASFCs) in the brain. The formation of ASFCs was found to decrease both asymmetry in occipital lobe responses to the photostimulus and the degree of neuroticism in subjects with panic attacks. The changes were reflected in decreasing values of the photic driving coefficient and recurrence rate and increasing values of the recurrence time. The improvement of the subject’s psychophysiological state after a course of ASFC activation was confirmed by a positive dynamics of psychophysiological testing data.

The study found that during the test with photostimulation, both in the presence of the phenomenon of reproduction of the rhythm of light flicker, and in its absence, the brain shows a pronounced reaction, as evidenced by significant changes in total bioelectric signal power in the cerebral hemispheres (CH). In the absence of the reaction of assimilation of the rhythm of light flicker in the subjects in most cases there is a decrease in the total signal strength in the CH. In the presence of a reaction of assimilation of the rhythm of light flicker, when the EEG visually observes oscillations that coincide with the frequency of the stimulus, the total signal strength in the hemispheres can both increase and decrease. At the same time, the largest increase in signal strength of individual rhythms during photostimulation is not always observed at the stimulation frequency. The results of the study suggest that the phenomenon of brain reproduction of the rhythm of light flicker observed on the EEG during photostimulation, and a decrease or increase in the total power of the bioelectric signal in the CH, are different physiological phenomena. This may mean that the absence of a response to the assimilation of the rhythm of light flicker during photostimulation is a more physiological response of the brain to the stimulus than the presence of such a reaction. This conclusion gives reason to believe that the presence of assimilation of the rhythm of light flicker at any of the frequencies during the test with photostimulation, and even more so, the presence of the 2nd and 3rd harmonics, is a manifestation of brain pathology. This approach to the evaluation of the sample with photostimulation correlates with the results of the test "with the eye open", which is also used to determine the reactivity of the human brain by exposure to the visual analyzer.

The objective of this study was to determine the effect of age at photostimulation on sexual maturity and performance of layer breeders. A total of 192 fourteen-wk-old White Leghorn (WL) breeder hens were randomly allocated to 4 treatments of 48 birds each, with 2 replicates per treatment. The birds were photostimulated at 16 (PS16), 18 (PS18), 20 (PS20), and 22 (PS22) wk of age. Four birds per treatment were randomly selected to evaluate sexual organ development at 1 D before photostimulation and 2, 4, and 6 wk after photostimulation. The ovary weight, large yellow follicles number (LYF), oviduct weight, and oviduct length of PS18 increased sharply after photostimulation. Conversely, the increase in PS16 was not observed until 2 wk after photostimulation. There was no difference in age at sexual maturity between treatments (P > 0.05). The PS16 had the longest interval (28 D) from photostimulation to 5% egg production, while PS22 reached 5% egg production 7 D before photostimulation. The PS22 had lower peak production (P = 0.02) and less egg production (P = 0.02) than other treatments. The PS16 had more broken and abnormal eggs (P = 0.01) and lower hatchability (P = 0.04) than other treatments. In conclusion, photostimulation at 16 and 22 wk of age decreases hatchability and egg production, respectively, and photostimulation at 18 wk is appreciated for the WL breeder hens.

The basolateral amygdala (BLA) and ventral hippocampal CA1 (vCA1) are cellularly and functionally diverse along their anterior–posterior and superficial-deep axes. Here, we find that anterior BLA (aBLA) and posterior BLA (pBLA) innervate deep-layer calbindin1-negative (Calb1−) and superficial-layer calbindin1-positive neurons (Calb1+) in vCA1, respectively. Photostimulation of pBLA–vCA1 inputs has an anxiolytic effect in mice, promoting approach behaviours during conflict exploratory tasks. By contrast, stimulating aBLA–vCA1 inputs induces anxiety-like behaviour resulting in fewer approaches. During conflict stages of the elevated plus maze task vCA1Calb1+ neurons are preferentially activated at the open-to-closed arm transition, and photostimulation of vCA1Calb1+ neurons at decision-making zones promotes approach with fewer retreats. In the APP/PS1 mouse model of Alzheimer’s disease, which shows anxiety-like behaviour, photostimulating the pBLA–vCA1Calb1+ circuit ameliorates the anxiety in a Calb1-dependent manner. These findings suggest the pBLA–vCA1Calb1+ circuit from heterogeneous BLA–vCA1 connections drives approach behaviour to reduce anxiety-like behaviour., Projections from the anterior and posterior basolateral amygdala (pBLA) to the ventral hippocampus CA1 (vCA1) are heterogenous. Here the authors show that activating the pathway from pBLA to vCA1 calbindin 1 positive neurons has an anxiolytic effect in approach-avoidance tasks in mice.

Photoswitchable drugs are small-molecule optical probes that enable chromatically selective control of drug efficacy. Such light-driven neuropharmacology normally uses UV-visible light. Here we report that luminescence from a NaYF4:TmYb nanoparticle can be used for “remote control” of the configuration of an azobenzene-based quaternary ammonium photochrome called “AAQ”. Normally the thermodynamically favored trans configuration of AAQ blocks voltage-gated potassium channels. Such activity is reduced by UV irradiation, due to the photochemical trans to cis isomerization generated by UV light. Since cis-AAQ absorbs more blue-green light, this wavelength range can be used to reverse the effects of UV light. We found that in place of such direct photostimulation, the blue luminescence from NaYF4:TmYb upconverting nanoparticles could drive AAQ activation inside living cells so as to enable bi-directional control of voltage-gated ion channels using UV and near-infrared light.

The future of brain research lies in the application of new technologies drawing from the latest developments in biology, physics and engineering to advance our understanding of how this complex organ processes, integrates and transfers information. Among these, optogenetics is a groundbreaking technology that allows using light to selectively activate neurons in the cortex of transgenic animals, usually mice, to observe its effect in large biological networks. A new research paradigm drawing from these advances consists of synchronizing optogenetic stimulation with electrophysiology recordings, to close the loop and to regulate the neural microcircuits, or to repair them. Such an approach holds promise to accelerate the development of new therapeutics against brain diseases by enabling entirely new experimental research scenarios with freely behaving animal models. As a result, the development of advanced wireless microelectronic implantable systems to elicit, extract and process brain data in real time has become a source of significant interest. This paper reviews the design challenges and the state-of-the-art technology in this field. We present the design of a complete electro-optic device for preforming optogenetics and multichannel electrophysiology in a closed-loop (CL) system with live neurons. We cover the design of the different CMOS integrated building blocks involved in this system to perform photostimulation and multichannel neural recording in parallel. We describe advanced hardware strategies to perform action potential (AP) detection, neural data compression and AP sorting in real-time, over several parallel recording channels for enabling real-time CL neural control. Finally, we present CL experimental results obtained in vivo with an electro-optic prototype.

Optical control of neural ensemble activity is crucial for understanding brain function and disease, yet no technology can achieve optogenetic control of very large numbers of neurons at extremely fast rate over a large volume. State-of-the-art multiphoton holographic optogenetics requires high power illumination that only addresses relatively small populations of neurons in parallel. Conversely, one-photon holographic techniques can stimulate more neurons with 2-3 orders lower power, but with a trade-off between resolution and addressable volume. Perhaps most problematically, two-photon holographic optogenetic systems are extremely expensive and sophisticated which has precluded their broader adoption in the neuroscience community. To address this technical gap, we introduce a new one-photon light sculpting technique, Three- Dimensional Multi-site random Access Photostimulation (3D-MAP), that overcomes these limitations by modulating light dynamically, both in the spatial and in the angular domain at multi-kHz rates. We use 3D-MAP to interrogate neural circuits in 3D and demonstrate simultaneous photostimulation and imaging of dozens of user-selected neurons in the intact mouse brain in vivo with high spatiotemporal resolution. 3D-MAP could be broadly adopted for high-throughput all-optical interrogation of brain circuits owing to its powerful combination of scale, speed, simplicity, and cost.

Much has been reported about optogenetic based cardiac arrhythmia treatment and the corresponding characterization of photostimulation parameters, but still, our capacity to interact with the underlying spatiotemporal excitation patterns relies mainly on electrical and/or pharmacological approaches. However, these well-established treatments have always been an object of somehow heated discussions. Though being acutely life-saving, they often come with potential side-effects leading to a decreased functionality of the complex cardiac system. Recent optogenetic studies showed the feasibility of the usage of photostimulation as a defibrillation method with comparatively high success rates. Although, these studies mainly concentrated on the description as well as on the comparison of single photodefibrillation approaches, such as locally focused light application and global illumination, less effort was spent on the description of excitation patterns during actual photostimulation. In this study, the authors implemented a multi-site photodefibrillation technique in combination with Multi-Lead electrocardiograms (ECGs). The technical connection of real-time heart rhythm measurements and the arrhythmia counteracting light control provides a further step toward automated arrhythmia classification, which can lead to adaptive photodefibrillation methods. In order to show the power effectiveness of the new approach, transgenic murine hearts expressing channelrhodopsin-2 ex vivo were investigated using circumferential micro-LED and ECG arrays. Thus, combining the best of two methods by giving the possibility to illuminate either locally or globally with differing pulse parameters. The optical technique presented here addresses a number of challenges of technical cardiac optogenetics and is discussed in the context of arrhythmic development during photostimulation.

The blood–brain barrier (BBB) limits the delivery of majority of cancer drugs and thereby complicates brain tumor treatment. The nasal-brain-lymphatic system is discussed as a pathway for brain drug delivery overcoming the BBB. However, in most cases, this method is not sufficient to achieve a therapeutic effect due to brain drug delivery in a short distance. Therefore, it is necessary to develop technologies to overcome the obstacles facing nose-to-brain delivery of promising pharmaceuticals. In this study, we clearly demonstrate intranasal delivery of liposomes to the mouse brain reaching glioblastoma (GBM). In the experiments with ablation of the meningeal lymphatic network, we report an important role of meningeal pathway for intranasal delivery of liposomes to the brain. Our data revealed that GBM is characterized by a dramatic reduction of intranasal delivery of liposomes to the brain that was significantly improved by near-infrared (1267 nm) photostimulation of the lymphatic vessels in the area of the cribriform plate and the meninges. These results open new perspectives for non-invasive improvement of efficiency of intranasal delivery of cancer drugs to the brain tissues using nanocarriers and near-infrared laser-based therapeutic devices, which are commercially available and widely used in clinical practice. RSF RFBR RF Governmental Grant

In deep tissue imaging, pulsed near-infrared lasers commonly provide high peak powers needed for nonlinear absorption, but average power and linear absorption can be limiting factors for tissue damage through heat. We implemented intra-cavity dumping within a mode-locked Ti:Sapphire laser used for two-photon computer generated holography stimulation. This system enables photostimulation in which pulse energy, average power, and repetition rate can each be varied and harnessed as degrees of freedom. We demonstrate how this system provides a new dimension of temporal control in photostimulation experiments to alter the ratio of nonlinear to linear light-tissue interactions, namely by tuning the laser repetition rate between single-shot and ≈ 3 MHz. Repetition rates below 1 MHz, yielding pulse energies over 60 nJ, facilitated holographic projections with more regions of interest than the highest repetition rate of 3 MHz. Even lower repetition rates ( ≈ 10 kHz) diminished thermal load on the sample, as characterized by quantification of heat shock protein expression in zebrafish tissue.

This article focuses on the problem of the preservation of visual acuity and fatigue prevention in professional activity which requires high responsibility. The implementation of the method of brain photostimulation in the system of aviation personnel rehabilitation has been suggested following the investigation of visual analyzer stimulation by pulses of red, green, and blue light in the α-rhythm range. The goal of the present study was to improve vision and general psychophysiological state and to determine the length of the photostimulation course required to achieve a reliable effect. The duration of the sessions of electrostimulation was 10 min daily for several days. The effectiveness of the stimulation has been evaluated before and after the session using the WAM questionnaire and an alternative psychophysiological scale. It has been found that the course of stimulation of visual analyzer with blue, green, and red light pulses at the frequency of 10–16 Hz led to an improved psychophysiological state of the subjects. The repeated exposure to photostimulation had a cumulative effect and led to a significant improvement in well-being of all the subjects who underwent the photostimulation course of at least 6 sessions.

With the discovery of optogenetics, using light becomes essential to study and control neural activity and connectivity. However, the complexity of the brain circuits demands advanced optical methods for detailed investigation. One of the most significant optical challenges is to address multiple targets with cellular resolution and high temporal precision in deep brain regions. During this thesis, I worked on three new optical systems to provide a possible answer to some of these technical challenges. First, we developed a new system to multiplex temporally focused light shapes (MTF-LS) for precise 3D photostimulation of neurons. Thanks to the flexibility of this new approach, different light-shaping methods can be applied: either computer-generated holography (CGH) or speckle-free generalized phase contrast. With these two approaches, the system was limited to multiplex only one shape at the time. To solve this issue we demonstrate an innovative amplitude/phase modulation technique, to multiplex different shapes in 3D. Due to the absorption and scattering, it is difficult to stimulate cells beyond ~ 600 µm of brain tissue with two-photon (2P) stimulation technique. Facing similar limitations in imaging, other laboratories used gradient index (GRIN) lenses implanted in the brain to access deep regions. Thus we develop a new in-depth photostimulation method, by coupling a GRIN lens with the MTF-LS previously demonstrated. This system represented the first microendoscope capable of generating tens of axially confined 2P excitation patterns matching target neuronal soma in a 3D volume for in-depth experiments. Third, to manipulate neuronal activity at sub-millisecond temporal scales and large cell populations, we built a new system using ultra-fast sequential light targeting (FLiT). We managed to control the spike delay among two cells with s temporal resolution. We also demonstrate a new stimulation protocol where the illumination time optimization allows to stimulate five times more cells than conventional static illumination for the same laser power., Avec la découverte de l'optogénétique, l’utilisation de la lumière est devenue essentielle pour étudier et contrôler l'activité et la connectivité neuronales. Cependant, la complexité des circuits cérébraux exige d’employer des méthodes optiques avancées pour toute investigation approfondie de son fonctionnement. C’est pourquoi, l'un des plus grands défis optiques est d'atteindre des cibles multiples avec une résolution cellulaire et une bonne précision temporelle dans les régions les plus profondes du cerveau. Au cours de cette thèse, j'ai travaillé sur trois nouveaux systèmes optiques afin d'apporter une réponse possible à certains de ces défis techniques. Premièrement, nous avons développé un nouveau système de génération de formes lumineuses focalisées dans le temps (MTF-LS) pour la photostimulation précise en 3D des neurones. Grâce à la flexibilité de cette nouvelle approche, différentes méthodes de modelage de la lumière ont put être utilisées: l'holographie générée par ordinateur (CGH) ou le contraste de phase généralisé. Avec ces deux approches, le système était limité à la multiplication en 3D d'une seule forme à la fois. Pour résoudre ce problème, nous avons proposé une technique innovante de modulation amplitude/phase, pour générer différentes formes en 3D. En raison de l'absorption et de la diffusion, il est difficile de stimuler des cellules au-delà de ~ 600 µm de tissu cérébral avec une méthode de stimulation à deux photons (2P). Face à des limitations similaires en matière d'imagerie, d'autres laboratoires ont utilisé des lentilles à gradient d'indice (GRIN) implantées dans le cerveau pour accéder à des régions profondes. Nous avons donc développé une nouvelle méthode de photostimulation en profondeur, en couplant une lentille GRIN avec le MTF-LS précédemment démontré. Ce système représente le premier microendoscope capable de générer des dizaines de sites d'excitation 2P, confinés axialement et correspondant aux dimensions du soma d’un neurone cible dans un volume 3D. Troisièmement, pour manipuler l'activité neuronale à des échelles temporelles inférieures à la milliseconde et/ou de grandes populations de cellules, nous avons construit un nouveau système utilisant le ciblage lumineux séquentiel ultra-rapide (FLiT). Nous sommes parvenus à contrôler le retard d’activation entre deux cellules avec une résolution temporelle de l'ordre de la microseconde. Nous avons également démontré un nouveau protocole de stimulation où l'optimisation du temps d'illumination permet de stimuler cinq fois plus de cellules que l'illumination statique conventionnelle pour la même puissance laser.

KEY POINTS We transfected preBotC SST+ neurons, which modulate respiratory pattern but are not rhythmogenic, with channelrhodopsin to investigate phase- and state-dependent modulation of breathing pattern in anesthetized and freely behaving mice in normoxia, hypoxia, and hypercapnia. In anesthetized mice, photostimulation during inspiration increased inspiratory duration and amplitude regardless of baseline breathing frequency, f, yet the effects were more robust at higher f. In anesthetized mice with low f (

Summary Axons form the long-range connections of biological neuronal networks, which are built through the developmental process of axon guidance. Here, we describe a protocol to precisely and non-invasively control axonal growth trajectories in live zebrafish embryos using focal light activation of a photoactivatable Rac1. We outline techniques for photostimulation, time-lapse imaging, and immunohistochemistry. These approaches enable engineering of long-range axonal circuitry or repair of defective circuits in living zebrafish, despite a milieu of competing endogenous signals and repulsive barriers. For complete details on the use and execution of this protocol, please refer to Harris et al. (2020)., Graphical abstract, Highlights • Directed outgrowth of axons using focal optogenetic activation of Rac1 • Time-lapse imaging of guided axonal growth in embryonic zebrafish • Immunohistochemical assessment of novel synapse formation, Axons form the long-range connections of biological neuronal networks, which are built through the developmental process of axon guidance. Here, we describe a protocol to precisely and non-invasively control axonal growth trajectories in live zebrafish embryos using focal light activation of a photoactivatable Rac1. We outline techniques for photostimulation, time-lapse imaging, and immunohistochemistry. These approaches enable engineering of long-range axonal circuitry or repair of defective circuits in living zebrafish, despite a milieu of competing endogenous signals and repulsive barriers.

Significant efforts have been committed to better understand and regulate insulin secretion as it has direct implications on diabetes. The first phase of biphasic insulin secretion in response to glucose lasts about 10 min, followed by a more sustained release persisting several hours. Attenuated insulin release in the first phase is typically associated with abnormal β-cells. While near-infrared photobiomodulation (PBM) demonstrates potential for multiple therapeutic applications, photostimulatory effects on α- and β-cells remain to be further elucidated. Herein, we demonstrate that 810 nm PBM exposure at fluence of 9 J/cm2 can elevate the intracellular reactive oxygen species within 15 min following photostimulation. In addition, calcium spiking showed an approximately 3-fold increase in both ATC1 (α-cells) and BTC6 (β-cells) and correlates with hormone secretion in response to PBM stimulation. Our findings could lay a foundation for the development of non-biologic therapeutics that can augment islet transplantation. This article is protected by copyright. All rights reserved.

Taste memory involves storing information through plasticity changes in the neural network of taste, including the insular cortex (IC) and ventral tegmental area (VTA), a critical provider of dopamine. Although a VTA-IC dopaminergic pathway has been demonstrated, its role to consolidate taste recognition memory remains poorly understood. We found that photostimulation of dopaminergic neurons in the VTA or VTA-IC dopaminergic terminals of TH-Cre mice increases the salience of a novel taste stimulus regardless of its hedonic value, without altering their taste palatability. Importantly, the inhibition of the D1-like receptor into the IC impairs the salience to facilitate consolidation of an aversive taste recognition memory. Finally, our results showed that VTA photostimulation improves the salience to consolidate a conditioned taste aversion memory through the D1-like receptor into the IC. It is concluded that the dopamine activity from the VTA into IC is required to increase the salience enabling the consolidation of a taste recognition memory. Notably, the D1-like receptor activity into the IC is required to consolidate both innate and learned aversive taste memories but not appetitive taste memory.

There is growing interest in organic semiconductor devices for light-mediated neuromodulation, such as for retinal stimulation. Here, the key working principles of these devices are discussed, as well as promising applications and outstanding challenges for the field., Organic semiconductors have generated substantial interest in neurotechnology and emerged as a promising approach for wireless neuromodulation in fundamental and applied research. Here, we summarise the range of applications that have been proposed so far, including retinal stimulation, excitation and inhibition of cultured neurons and regulation of biological processes in other non-excitable cells from animal and plant origins. We also discuss the key chemical and physical phenomena at the basis of the interaction between materials and cells. Finally, we provide an overview of future perspectives, exciting research opportunities and the remaining challenges hampering the translation of this blooming technology into the clinic and industry.

Laser photocoagulation is a safe method for the treatment of retinal disorders. We present a case of a 21-year-old woman with high myopia, retinal detachment in the right eye, and bilateral lattice degeneration. She underwent surgical repair in the right eye followed by bilateral retinal laser therapy. During laser photocoagulation of the left eye, she experienced a generalized tonic-clonic seizure for the first time in her life. She had a positive family history of epilepsy. Neurological examination and brain magnetic resonance imaging findings were normal, but an electroencephalogram revealed epileptogenic discharges, more frequent during photostimulation. She avoided flickering lights during the 2-year follow-up, without seizure recurrence. Approximately 5% of patients with epilepsy have photosensitive epilepsy, of whom a considerable proportion will experience seizures only during exposition to flashing lights. Laser photocoagulation was already successfully employed in an animal model of photosensitive epilepsy. Personal or family history of photosensitivity warrants a neurological consultation before retinal treatment with laser therapy. RESUMO Fotocoagulação a laser é método seguro para tratamento de retinopatias. Apresentamos o caso de uma mulher de 21 anos com alta miopia e degeneração lattice bilateral que sofreu descolamento de retina no olho direito e foi submetida a tratamento cirúrgico e ulterior laserterapia. Durante a fotocoagulação no olho esquerdo, ela teve uma convulsão tônico-clônica generalizada, a primeira em sua vida. Havia história familiar de epilepsia. O exame neurológico e a ressonância magnética de en céfalo foram normais, mas o electroencefalograma revelou descargas epileptogênicas, mais frequentes durante a fotoesti mulação. Ela evitou luzes piscantes durante os 2 anos subsequentes, sem recorrência de convulsões. Cerca de 5% dos pacientes com epilepsia têm fotossensibilidade. Proporção considerável deles terá convulsões somente durante exposição à luz piscante. Fotocoagulação a laser já foi empregada como modelo animal de sucesso para epilepsia fotossensível. Presença de fotossensibilidade na história pessoal ou familiar deve merecer avaliação neurológica antes do tratamento retiniano.

The deposition of amyloid-β (Aβ) in the brain is a risk factor for Alzheimer’s disease (AD). Therefore, new strategies for the stimulation of Aβ clearance from the brain can be useful in preventing AD. Transcranial photostimulation (PS) is considered a promising method for AD therapy. In our previous studies, we clearly demonstrated the PS-mediated stimulation of lymphatic clearing functions, including Aβ removal from the brain. There is increasing evidence that sleep plays an important role in Aβ clearance. Here, we tested our hypothesis that PS at night can stimulate Aβ clearance from the brain more effectively than PS during the day. Our results on healthy mice show that Aβ clearance from the brain occurs faster at night than during wakefulness. The PS course at night improves memory and reduces Aβ accumulation in the brain of AD mice more effectively than the PS course during the day. Our results suggest that night PS is a more promising candidate as an effective method in preventing AD than daytime PS. These data are an important informative platform for the development of new noninvasive and nonpharmacological technologies for AD therapy as well as for preventing Aβ accumulation in the brain of people with disorder of Aβ metabolism, sleep deficit, elderly age, and jet lag.