In vito fber photometry is a powerful technique to analyze the dy namics of population neurons during fiunctional study of neuroscience.Here,we introduced a detailed protocol for fiber photometry-based calciun reordin...In vito fber photometry is a powerful technique to analyze the dy namics of population neurons during fiunctional study of neuroscience.Here,we introduced a detailed protocol for fiber photometry-based calciun reording in freely moving mice,covering from virus injection,fiber stub insertion,optogenetical stimulation to data procurement and analysis.Furthemnore,we applied this protocol to explore neuronal activity of mice latenal-posterior(LP)thalaric nucleus in response to optogenetical stimulation of primary visual cortex(V1)neurons,and explore axon clusters activity of optogenetically evoked V1 neurons.Final confirmation of virus-based protein expression in V1 and precise fber insertion indicated that the surgery procedure of this protocol is reliable for functional calcium recording.The scripts for data analysis and some tips in our protocol are provided in details.Together,this protocol is simple,low-cost,and effective for neuronal activity detection by fiber photometry,which will hep neuroscience researchers to carry out fiunctional and behavioral study in vivo.展开更多
Generating diverse motor behaviors critical for survival is a challenge that confronts the central nervous system(CNS)of all animals.During movement execution,the CNS performs complex calculations to control a large n...Generating diverse motor behaviors critical for survival is a challenge that confronts the central nervous system(CNS)of all animals.During movement execution,the CNS performs complex calculations to control a large number of neuromusculoskeletal elements.The theory of modular motor control proposes that spinal interneurons are organized in discrete modules that can be linearly combined to generate a variety of behavioral patterns.These modules have been previously represented as stimulus-evoked force fields(FFs)comprising isometric limb-endpoint forces across workspace locations.Here,we ask whether FFs elicited by different stimulations indeed represent the most elementary units of motor control or are themselves the combination of a limited number of even more fundamental motor modules.To probe for potentially more elementary modules,we optogenetically stimulated the lumbosacral spinal cord of intact and spinalized Thy1-ChR2 transgenic mice(n=21),eliciting FFs from as many single stimulation loci as possible(20-70 loci per mouse)at minimally necessary power.We found that the resulting varieties of FFs defied simple categorization with just a few clusters.We used gradient descent to further decompose the FFs into their underlying basic force fields(BFFs),whose linear combination explained FF variability.Across mice,we identified 4-5 BFFs with partially localizable but overlapping representations along the spinal cord.The BFFs were structured and topographically distributed in such a way that a rostral-to-caudal traveling wave of activity across the lumbosacral spinal cord may generate a swing-to-stance gait cycle.These BFFs may represent more rudimentary submodules that can be flexibly merged to produce a library of motor modules for building different motor behaviors.展开更多
Optogenetics has revolutionized the field of neuroscience by enabling precise control of neural activity through light-sensitive proteins known as opsins.This review article discusses the fundamental principles of opt...Optogenetics has revolutionized the field of neuroscience by enabling precise control of neural activity through light-sensitive proteins known as opsins.This review article discusses the fundamental principles of optogenetics,including the activation of both excitatory and inhibitory opsins,as well as the development of optogenetic models that utilize recombinant viral vectors.A considerable portion of the article addresses the limitations of optogenetic tools and explores strategies to overcome these challenges.These strategies include the use of adeno-associated viruses,cell-specific promoters,modified opsins,and methodologies such as bioluminescent optogenetics.The application of viral recombinant vectors,particularly adeno-associated viruses,is emerging as a promising avenue for clinical use in delivering opsins to target cells.This trend indicates the potential for creating tools that offer greater flexibility and accuracy in opsin delivery.The adaptations of these viral vectors provide advantages in optogenetic studies by allowing for the restricted expression of opsins through cell-specific promoters and various viral serotypes.The article also examines different cellular targets for optogenetics,including neurons,astrocytes,microglia,and Schwann cells.Utilizing specific promoters for opsin expression in these cells is essential for achieving precise and efficient stimulation.Research has demonstrated that optogenetic stimulation of both neurons and glial cells-particularly the distinct phenotypes of microglia,astrocytes,and Schwann cells-can have therapeutic effects in neurological diseases.Glial cells are increasingly recognized as important targets for the treatment of these disorders.Furthermore,the article emphasizes the emerging field of bioluminescent optogenetics,which combines optogenetic principles with bioluminescent proteins to visualize and manipulate neural activity in real time.By integrating molecular genetics techniques with bioluminescence,researchers have developed methods to monitor neuronal activity efficiently and less invasively,enhancing our understanding of central nervous system function and the mechanisms of plasticity in neurological disorders beyond traditional neurobiological methods.Evidence has shown that optogenetic modulation can enhance motor axon regeneration,achieve complete sensory reinnervation,and accelerate the recovery of neuromuscular function.This approach also induces complex patterns of coordinated motor neuron activity and promotes neural reorganization.Optogenetic approaches hold immense potential for therapeutic interventions in the central nervous system.They enable precise control of neural circuits and may offer new treatments for neurological disorders,particularly spinal cord injuries,peripheral nerve injuries,and other neurodegenerative diseases.展开更多
Epilepsy,a common neurological disorder,is characterized by recurrent seizures that can lead to cognitive,psychological,and neurobiological consequences.The pathogenesis of epilepsy involves neuronal dysfunction at th...Epilepsy,a common neurological disorder,is characterized by recurrent seizures that can lead to cognitive,psychological,and neurobiological consequences.The pathogenesis of epilepsy involves neuronal dysfunction at the molecular,cellular,and neural circuit levels.Abnormal molecular signaling pathways or dysfunction of specific cell types can lead to epilepsy by disrupting the normal functioning of neural circuits.The continuous emergence of new technologies and the rapid advancement of existing ones have facilitated the discovery and comprehensive understanding of the neural circuit mechanisms underlying epilepsy.Therefore,this review aims to investigate the current understanding of the neural circuit mechanisms in epilepsy based on various technologies,including electroencephalography,magnetic resonance imaging,optogenetics,chemogenetics,deep brain stimulation,and brain-computer interfaces.Additionally,this review discusses these mechanisms from three perspectives:structural,synaptic,and transmitter circuits.The findings reveal that the neural circuit mechanisms of epilepsy encompass information transmission among different structures,interactions within the same structure,and the maintenance of homeostasis at the cellular,synaptic,and neurotransmitter levels.These findings offer new insights for investigating the pathophysiological mechanisms of epilepsy and enhancing its clinical diagnosis and treatment.展开更多
Spinal cord injury is a severe neurological disorder;however,current treatment methods often fail to restore nerve function effectively.Spinal cord stimulation via electrical signals is a promising therapeutic modalit...Spinal cord injury is a severe neurological disorder;however,current treatment methods often fail to restore nerve function effectively.Spinal cord stimulation via electrical signals is a promising therapeutic modality for spinal cord injury.Based on similar principles,this review aims to explore the potential of optical and acoustic neuromodulation techniques,emphasizing their benefits in the context of spinal cord injury.Photoacoustic imaging,renowned for its noninvasive nature,high-resolution capabilities,and cost-effectiveness,is well recognized for its role in early diagnosis,dynamic monitoring,and surgical guidance in stem cell therapies for spinal cord injury.Moreover,photoacoustodynamic therapy offers multiple pathways for tissue regeneration.Optogenetics and sonogenetics use genetic engineering to achieve precise neuronal activation,while photoacoustoelectric therapy leverages photovoltaic materials for electrical modulation of the nervous system,introducing an innovative paradigm for nerve system disorder management.Collectively,these advancements represent a transformative shift in the diagnosis and treatment of spinal cord injury,with the potential to significantly enhance nerve function remodeling and improve patient outcomes.展开更多
Optogenetic has been widely applied in various pathogenesis investigations of neuropathic diseases since its accurate and targeted regulation of neuronal activity.However,due to the mismatch between the soft tissues a...Optogenetic has been widely applied in various pathogenesis investigations of neuropathic diseases since its accurate and targeted regulation of neuronal activity.However,due to the mismatch between the soft tissues and the optical waveguide,the long-term neural regulation within soft tissue(such as brain and spinal cord)by implantable optical fibers is a large challenge.Herein,we designed a modulus selfadaptive hydrogel optical fiber(MSHOF)with tunable mechanical properties(Young’modulus was tunable in the range of 0.32-10.56MPa)and low light attenuation(0.12-0.21 dB/cm,472nm laser light),which adapts to light transmission under soft tissues.These advantages of MSHOF can ensure the effectiveness of optogenetic stimulation meanwhile safeguarding the safety of the brain/materials interaction interface.In addition,this work provides more design possibilities of MSHOF for photogenetic stimuli and has significant application prospects in photomedical therapy.展开更多
In this study,we aimed to develop an in vivo electrophysiological bone-nerve preparation to record the activity of peripheral sensory neurons that innervate the murine tibia.A small nerve that innervates the tibial ma...In this study,we aimed to develop an in vivo electrophysiological bone-nerve preparation to record the activity of peripheral sensory neurons that innervate the murine tibia.A small nerve that innervates the tibial marrow cavity was identified in isoflurane-anesthetized C57BL/6 mice,and placed over a platinum hook electrode for extracellular recording.Whole-nerve activity was amplified,filtered and sampled at 20 kHz using PowerLab(ADInstruments).A cannula was placed into the marrow cavity to deliver mechanical stimuli(by pressurizing with injection of saline)and/or capsaicin.Optical stimulation was achieved by application of 473 nm blue light(1 Hz,0.25-0.5 ms,0-12.5 mW/mm)to the tibial marrow cavity in Wnt1-Cre;loxP-ChR2 mice.Murine bone afferent neurons responded to high threshold noxious mechanical stimulation,coded for the intensity of mechanical stimulation,could be sensitized by capsaicin,and did not suffer stimulus-evoked fatigue at 10-minute interstimulus intervals.Electrical and optical stimulation within the marrow cavity evoked action potentials with conduction velocities in the Aδand/or C fiber range.These new approaches to recording the activity of bone afferent neurons will allow us to take advantage of transgenic and optogenetic tools to further our understanding of mechanisms that generate and maintain bone pain in the future.展开更多
Depression is a multifaceted disorder with a largely unresolved etiology influenced by a complex interplay of pathogenic factors.Despite decades of research,it remains a major condition that significantly diminishes p...Depression is a multifaceted disorder with a largely unresolved etiology influenced by a complex interplay of pathogenic factors.Despite decades of research,it remains a major condition that significantly diminishes patients’quality of life.Advances in optogenetics have introduced a powerful tool for exploring the neural mechanisms underlying depression.By selectively expressing optogenes in specific cell types in mice,researchers can study the roles of these cells through targeted light stimulation,offering new insights into central nervous system disorders.The use of viral vectors to express opsins in distinct neuronal subtypes enables precise activation or inhibition of these neurons via light.When combined with behavioral,morphological,and electrophysiological analyses,optogenetics provides an invaluable approach to investigating the neural mechanisms of psychiatric conditions.This review synthesizes current research on the application of optogenetics to understand the mechanisms of depression.This study aims to enhance our knowledge of optogenetic strategies for regulating depression and advancing antidepressant research.展开更多
Objective:This study aims to establish an economically viable and easily accessible adult animal model for optogenetic activation of auditory neurons using adeno-associated viruses(AAVs)carrying Ch R2(H134R)to explore...Objective:This study aims to establish an economically viable and easily accessible adult animal model for optogenetic activation of auditory neurons using adeno-associated viruses(AAVs)carrying Ch R2(H134R)to explore the potential of cochlear optogenetics as a hearing restoration technology.Methods:Healthy adult guinea pigs were used in the experiments.The viral vector AAV2/8-Ch R2(H134R)-h Syn-e YFP was administered to the right cochlea via the round window membrane.The confocal microscopy and reverse transcription polymerase chain reaction(RT-PCR)were utilized to analyze the Ch R2(H134R)expression localized to spiral ganglion neurons(SGNs).The auditory pathway activation was assessed by recording the optical compound action potential(oCAP)and acoustic compound action potential(a CAP)at various laser intensities.Results:The Ch R2(H134R)-e YFP expression was confirmed in 90%of the tested animals,localized to the SGNs of the injected ear.Higher m RNA levels of Ch R2(H134R)and e YFP were observed in the injected ear compared to the non-injected ear,while actin(Actb)m RNA levels were not significantly different.The o CAP was successfully elicited by a 470 nm blue light laser stimulus,with similar amplitudes and latency periods to those of a CAPs when the o CAP was evoked by 5.80 m W blue light and the a CAP was evoked by a 40 d B SPL click.The amplitudes of o CAPs increased with increasing laser intensity.Conclusion:This study demonstrates the viability of optogenetic activation of the auditory system in adult guinea pigs through the transduction of AAV-Ch R2(H134R)in SGNs.Cochlear optogenetics demonstrates potential as a hearing restoration technology,providing a basis for further clinical research and opening new avenues for investigation.展开更多
The hippocampus is the brain structure that is responsible for the formation of learning memories.Sleep disorders leading to cognitive impairment are strongly associated with the hippocampus.Phototherapy offers a new ...The hippocampus is the brain structure that is responsible for the formation of learning memories.Sleep disorders leading to cognitive impairment are strongly associated with the hippocampus.Phototherapy offers a new physical therapy for the treatment of sleep disorders,with the advantages of being noninvasive and having few side effects.However,the mechanism by which phototherapy improves cognitive impairment caused by sleep disorders remains unclear.In this study,we used phototherapy combined with optogenetic technology to investigate the effect of noninvasive phototherapy on cognitive functions in sleep-deprived mice.Our results suggest that phototherapy might improve cognitive functions in sleep-deprived mice by modulating the hippocampus.Our study expands the research progress on noninvasive phototherapy for the treatment of sleep disorders.展开更多
This study is based on wireless optogenetic technology,utilizing the CRY2/CIB1 photosensitive system to achieve spatiotemporal control of PD-L1 expression.In vitro experiments showed that the surface PD-L1 positivity ...This study is based on wireless optogenetic technology,utilizing the CRY2/CIB1 photosensitive system to achieve spatiotemporal control of PD-L1 expression.In vitro experiments showed that the surface PD-L1 positivity rate of cells increased from 28.6±3.1%to 67.3±5.4%(P<0.001).In animal experiments,the terminal tumor volume in the light exposure group was 450±90 mm3,with a tumor inhibition rate of approximately 49.4%(P<0.001),and the median survival was extended to 32 days(compared to 24 days in the control group,P=0.004).Immunological tests revealed a significant increase in CD8+T cell infiltration(112±18 vs 52±10 cells/HPF,P<0.01),a 30%decrease in the proportion of Tregs(P<0.05),and an increase in the M1/M2 macrophage ratio to 1.8.The results suggest that the wireless optogenetic system can not only precisely regulate PD-L1 but also remodel the tumor immune microenvironment,providing a new approach for precise immunotherapy of GBM.展开更多
Micro-scaled light-emitting diode(LED)technology has emerged as a transformative tool in biomedical applications,offering innovative solutions across disease surveillance,treatment,and symptom rehabilitation.In diseas...Micro-scaled light-emitting diode(LED)technology has emerged as a transformative tool in biomedical applications,offering innovative solutions across disease surveillance,treatment,and symptom rehabilitation.In disease surveillance,micro-scaled LEDs enable real-time,noninvasive monitoring of physiological parameters through wearable devices,such as skin-like health patches and wireless pulse oximeters;these systems leverage the miniaturization,low power consumption,and high precision of micro-scaled LEDs to track heart rate,blood oxygenation,and neural activity with exceptional accuracy.For disease treatment,micro-scaled LEDs play a pivotal role in optogenetic stimulation and phototherapy.By delivering specific light wavelengths,they enable precise cellular control for cardiac regeneration,neural modulation,and targeted cancer therapies,such as photodynamic therapy with reduced invasiveness.In addition,wireless micro-scaled LED systems facilitate localized and sustained treatments for conditions such as diabetic retinopathy.For symptom rehabilitation,micro-scaled LED-based devices enhance functional and aesthetic outcomes,exemplified by optical cochlear implants for high-resolution hearing restoration and flexible photostimulation patches for hair regrowth.The performance of micro-scale LEDs also brings new possibilities to the field of brain–computer interface.These applications highlight the versatility of micro-scaled LEDs in improving patient quality of life through minimally invasive,energy-efficient,and biocompatible solutions.Although there are still challenges in long-term stability and scalability,the integration of micro-scaled LEDs with advanced biomedical technologies promises to redefine personalized healthcare and therapeutic efficacy.展开更多
Dear Editor,It is now well established that optogenetic stimulation can achieve precise intervention and modulate the activity of local neurons or neural circuits in the brain.Although this technique holds promise for...Dear Editor,It is now well established that optogenetic stimulation can achieve precise intervention and modulate the activity of local neurons or neural circuits in the brain.Although this technique holds promise for clinical therapy for neurological and psychiatric disorders,it requires the expression of lightsensitive proteins(such as channel rhodopsin)or photoactivatable chemicals(such as caged neurotransmitters)in the targeted brain regions[1].展开更多
Background:The development of ketamine-like rapid antidepressants holds promise for enhancing the therapeutic efficacy of depression,but the underlying cellular and molecular mechanisms remain unclear.Implicated in de...Background:The development of ketamine-like rapid antidepressants holds promise for enhancing the therapeutic efficacy of depression,but the underlying cellular and molecular mechanisms remain unclear.Implicated in depression regulation,the neuropeptide pituitary adenylate cyclase-activating polypeptide(PACAP)is investigated here to examine its role in mediating the rapid antidepressant response.Methods:The onset of antidepressant response was assessed through depression-related behavioral paradigms.The signaling mechanism of PACAP in the hippocampal dentate gyrus(DG)was evaluated by utilizing site-directed gene knockdown,pharmacological interventions,or optogenetic manipulations.Overall,446 mice were used for behavioral and molecular signaling testing.Mice were divided into control or experimental groups randomly in each experiment,and the experimental manipulations included:chronic paroxetine treatments(4 d,9 d,14 d)or a single treatment of ketamine;social defeat or lipopolysaccharides-injection induced depression models;different doses of PACAP(0.4 ng/site,2 ng/site,4 ng/site;microinjected into the hippocampal DG);pharmacological intra-DG interventions(CALM and PACAP6-38);intra-DG viral-mediated PACAP RNAi;and opotogenetics using channelrhodopsins 2(ChR2)or endoplasmic natronomonas halorhodopsine 3.0(eNpHR3.0).Behavioral paradigms included novelty suppressed feeding test,tail suspension test,forced swimming test,and sucrose preference test.Western blotting,ELISA,or quantitative real-time PCR(RT-PCR)analysis were used to detect the expressions of proteins/peptides or genes in the hippocampus.Results:Chronic administration of the slow-onset antidepressant paroxetine resulted in an increase in hippocampal PACAP expression,and intra-DG blockade of PACAP attenuated the onset of the antidepressant response.The levels of hippocampal PACAP expression were reduced in both two distinct depression animal models and intra-DG knockdown of PACAP induced depression-like behaviors.Conversely,a single infusion of PACAP into the DG region produced a rapid and sustained antidepressant response in both normal and chronically stressed mice.Optogenetic intra-DG excitation of PACAP-expressing neurons instantly elicited antidepressant responses,while optogenetic inhibition induced depression-like behaviors.The longer optogenetic excitation/inhibition elicited the more sustained antidepressant/depression-like responses.Intra-DG PACAP infusion immediately facilitated the signaling for rapid antidepressant response by inhibiting calcium/calmodulin-dependent protein kinaseⅡ(CaM KⅡ)-eukaryotic elongation factor 2(eEF2)and activating the mammalian target of rapamycin(mTOR).Pre-activation of CaMKⅡsignaling within the DG blunted PACAP-induced rapid antidepressant response as well as eEF2-mTOR-brain-derived neurotrophic factor(BDNF)signaling.Finally,acute ketamine treatment upregulated hippocampal PACAP expression,whereas intraDG blockade of PACAP signaling attenuated ketamine’s rapid antidepressant response.Conclusions:Activation of hippocampal PACAP signaling induces a rapid antidepressant response through the regulation of CaMKⅡinhibition-governed eEF2-mTOR-BDNF signaling.展开更多
The basal ganglia(BG) act as a cohesive functional unit that regulates motor function,habit formation,and reward/addictive behaviors. However,it is still not well understood how the BG maintains wakefulness and suppre...The basal ganglia(BG) act as a cohesive functional unit that regulates motor function,habit formation,and reward/addictive behaviors. However,it is still not well understood how the BG maintains wakefulness and suppresses sleep to achieve al these fundamental functions until genetical y engineered systems developed these years. Significant research efforts have recently been directed at developing genetic-molecular tools to achieve reversible and cell-type specific in vivo silencing or activation of neurons in behaving animals. Optogenetic tools can be used both to specifically activate or inhibit neurons of interest and identify functional synaptic connectivity between specific neuronal populations,both in vivo and in brain slices. Another recently developed system by Roth and colleagues permits the selective and ″remote″ manipulation(activation and silencing) of neuronal activity via all 3 major GPCR signaling pathways(G_i,G_s and G_q). These so-called ″ designer receptors exclusively activated by designer drugs″(DREADD) involve mutant GPCRs that do not respond to their endogenous ligands but are responsive to otherwise inert biological compounds. Recently,we demonstrated the essential roles and the neural pathways of the neurons expressing adenosine A_(2A) receptors or dopamine D_1 receptors in the BG for sleep-wake regulation using the genetically engineered systems including optogenetics and DREADD. We proposed a plausible model in which the caudate-putamen and the nucleus accumbens integrates behavioral processes with sleep/wakefulness through adenosine and dopamine receptors.展开更多
Many complex behaviors that do not require learning are displayed and are termed innate. Although traditionally the subject matter of ethology, innate behaviors offer a unique entry point for neuroscientists to dissec...Many complex behaviors that do not require learning are displayed and are termed innate. Although traditionally the subject matter of ethology, innate behaviors offer a unique entry point for neuroscientists to dissect the physiological mechanisms governing complex behaviors. Since the last century, converging evidence has implicated the hypothalamus as the central brain area that controls innate behaviors. Recent studies using cutting-edge tools have revealed that genetically-defined populations of neurons residing in distinct hypothalamic nuclei and their associated neural pathways regulate the initiation and maintenance of diverse behaviors including feeding, sleep, aggression, and parental care. Here, we review the newly-defined hypothalamic pathways that regulate each innate behavior. In addition, emerging general principles of the neural control of complex behaviors are discussed.展开更多
Although extensively studied, the exact role of sleep in learning and memory is still not very clear. Sleep deprivation has been most frequently used to explore the effects of sleep on learning and memory, but the res...Although extensively studied, the exact role of sleep in learning and memory is still not very clear. Sleep deprivation has been most frequently used to explore the effects of sleep on learning and memory, but the results from such studies are inevitably complicated by concurrent stress and distress. Furthermore, it is not clear whether there is a strict time-window between sleep and memory consolidation. In the present study we were able to induce time-locked slow-wave sleep(SWS) in mice by optogenetically stimulating GABAergic neurons in the parafacial zone(PZ), providing a direct approach to analyze the influences of SWS on learning and memory with precise time-windows. We found that SWS induced by light for 30 min immediately or 15 min after the training phase of the object-in-place task significantly prolonged the memory from 30 min to 6 h. However, induction of SWS 30 min after the training phase did not improve memory, suggesting a critical time-window between the induction of a brief episode of SWS and learning for memory consolidation.Application of a gentle touch to the mice during light stimulation to prevent SWS induction also failed to improve memory, indicating the specific role of SWS,but not the activation of PZ GABAergic neurons itself, in memory consolidation. Similar influences of light-induced SWS on memory consolidation also occurred for Y-maze spatial memory and contextual fear memory, but not for cued fear memory. SWS induction immediately before the test phase had no effect on memory performance, indicating that SWS does not affect memory retrieval. Thus, by induction of a brief-episode SWS we have revealed a critical time window for the consolidation of hippocampusdependent memory.展开更多
Alzheimer’s disease(AD)is the most common neurodegenerative disorder and there is currently no cure.Neural circuit dysfunction is the fundamental mechanism underlying the learning and memory deficits in patients with...Alzheimer’s disease(AD)is the most common neurodegenerative disorder and there is currently no cure.Neural circuit dysfunction is the fundamental mechanism underlying the learning and memory deficits in patients with AD.Therefore,it is important to understand the structural features and mechanisms underlying the deregulated circuits during AD progression,by which new tools for intervention can be developed.Here,we briefly summarize the most recently established cutting-edge experimental approaches and key techniques that enable neural circuit tracing and manipulation of their activity.We also discuss the advantages and limitations of these approaches.Finally,we review the applications of these techniques in the discovery of circuit mechanisms underlyingβ-amyloid and tau pathologies during AD progression,and as well as the strategies for targeted AD treatments.展开更多
Ion channels present in the plasma membrane are responsible for integration and propagation of electric signals,which transmit information in nerve cells.Malfunction of these ion channels leads to many neurological di...Ion channels present in the plasma membrane are responsible for integration and propagation of electric signals,which transmit information in nerve cells.Malfunction of these ion channels leads to many neurological diseases.Recently,optogenetic technology has gained a lot of attention for the manipulation of neuronal circuits.Optogenetics is a neuromodulation approach that has been developed to control neuronal functions and activities using light.The lanthanide-doped upconversion nanoparticles(UCNPs)absorb low energy photons in near-infrared(NIR) window and emit high energy photons in the visible spectrum region via nonlinear processes.In the last few decades,UCNPs have gained great attention in various bio-medical applications such as bio-imaging,drug delivery and optogenetics.The near-infrared illumination is considered more suitable for optogenetics application,due to its lower degree of light attenuation and higher tissue penetration compared to visible light.Therefore,UCNPs have been considered as the new promising candidates for optogenetics applications.Upconversion nanoparticlemediated optogenetic systems provide a great opportunity to manipulate the ion channel in deep tissue.Herein,we summarize the upconversion photoluminescence in lanthanide doped nanomaterials and its mechanisms and several approaches adopted to tune emission color or enhance upconversion efficiency.Recent advances of lanthanide-doped UCNPs design strategy and their mechanism are reviewed.Then,we discuss the neural circuitry modulation using upconversion nanoparticles mediated optogenetics.Moreover,the future perspectives towards optogenetics are also included.展开更多
Pain is an unpleasant sensory and emotional experience associated with,or resembling that associated with,actual or potential tissue damage.The processing of pain involves complicated modulation at the levels of the p...Pain is an unpleasant sensory and emotional experience associated with,or resembling that associated with,actual or potential tissue damage.The processing of pain involves complicated modulation at the levels of the periphery,spinal cord,and brain.The pathogenesis of chronic pain is still not fully understood,which makes the clinical treatment challenging.Optogenetics,which combines optical and genetic technologies,can precisely intervene in the activity of specific groups of neurons and elements of the related circuits.Taking advantage of optogenetics,researchers have achieved a body of new findings that shed light on the cellular and circuit mechanisms of pain transmission,pain modulation,and chronic pain both in the periphery and the central nervous system.In this review,we summarize recent findings in pain research using optogenetic approaches and discuss their significance in understanding the pathogenesis of chronic pain.展开更多
基金supported by the National Natural Science Foundation of China (Grant Nos.31371106 and 91632110)HZAU Independent Innovation Fund (2014BQ019).
文摘In vito fber photometry is a powerful technique to analyze the dy namics of population neurons during fiunctional study of neuroscience.Here,we introduced a detailed protocol for fiber photometry-based calciun reording in freely moving mice,covering from virus injection,fiber stub insertion,optogenetical stimulation to data procurement and analysis.Furthemnore,we applied this protocol to explore neuronal activity of mice latenal-posterior(LP)thalaric nucleus in response to optogenetical stimulation of primary visual cortex(V1)neurons,and explore axon clusters activity of optogenetically evoked V1 neurons.Final confirmation of virus-based protein expression in V1 and precise fber insertion indicated that the surgery procedure of this protocol is reliable for functional calcium recording.The scripts for data analysis and some tips in our protocol are provided in details.Together,this protocol is simple,low-cost,and effective for neuronal activity detection by fiber photometry,which will hep neuroscience researchers to carry out fiunctional and behavioral study in vivo.
基金supported by the CUHK Faculty of Medicine Faculty Innovation Award FIA2016/A/04(to V.C.K.C.)Group Research Scheme NL/JW/rc/grs1819/0426/19hc(to V.C.K.C.)The Hong Kong Research Grants Council 24115318,CUHK-R4022-18,14114721,and 14119022(to V.C.K.C)。
文摘Generating diverse motor behaviors critical for survival is a challenge that confronts the central nervous system(CNS)of all animals.During movement execution,the CNS performs complex calculations to control a large number of neuromusculoskeletal elements.The theory of modular motor control proposes that spinal interneurons are organized in discrete modules that can be linearly combined to generate a variety of behavioral patterns.These modules have been previously represented as stimulus-evoked force fields(FFs)comprising isometric limb-endpoint forces across workspace locations.Here,we ask whether FFs elicited by different stimulations indeed represent the most elementary units of motor control or are themselves the combination of a limited number of even more fundamental motor modules.To probe for potentially more elementary modules,we optogenetically stimulated the lumbosacral spinal cord of intact and spinalized Thy1-ChR2 transgenic mice(n=21),eliciting FFs from as many single stimulation loci as possible(20-70 loci per mouse)at minimally necessary power.We found that the resulting varieties of FFs defied simple categorization with just a few clusters.We used gradient descent to further decompose the FFs into their underlying basic force fields(BFFs),whose linear combination explained FF variability.Across mice,we identified 4-5 BFFs with partially localizable but overlapping representations along the spinal cord.The BFFs were structured and topographically distributed in such a way that a rostral-to-caudal traveling wave of activity across the lumbosacral spinal cord may generate a swing-to-stance gait cycle.These BFFs may represent more rudimentary submodules that can be flexibly merged to produce a library of motor modules for building different motor behaviors.
基金supported by a grant from the Russian Science Foundation,No.23-75-10041(to MY)。
文摘Optogenetics has revolutionized the field of neuroscience by enabling precise control of neural activity through light-sensitive proteins known as opsins.This review article discusses the fundamental principles of optogenetics,including the activation of both excitatory and inhibitory opsins,as well as the development of optogenetic models that utilize recombinant viral vectors.A considerable portion of the article addresses the limitations of optogenetic tools and explores strategies to overcome these challenges.These strategies include the use of adeno-associated viruses,cell-specific promoters,modified opsins,and methodologies such as bioluminescent optogenetics.The application of viral recombinant vectors,particularly adeno-associated viruses,is emerging as a promising avenue for clinical use in delivering opsins to target cells.This trend indicates the potential for creating tools that offer greater flexibility and accuracy in opsin delivery.The adaptations of these viral vectors provide advantages in optogenetic studies by allowing for the restricted expression of opsins through cell-specific promoters and various viral serotypes.The article also examines different cellular targets for optogenetics,including neurons,astrocytes,microglia,and Schwann cells.Utilizing specific promoters for opsin expression in these cells is essential for achieving precise and efficient stimulation.Research has demonstrated that optogenetic stimulation of both neurons and glial cells-particularly the distinct phenotypes of microglia,astrocytes,and Schwann cells-can have therapeutic effects in neurological diseases.Glial cells are increasingly recognized as important targets for the treatment of these disorders.Furthermore,the article emphasizes the emerging field of bioluminescent optogenetics,which combines optogenetic principles with bioluminescent proteins to visualize and manipulate neural activity in real time.By integrating molecular genetics techniques with bioluminescence,researchers have developed methods to monitor neuronal activity efficiently and less invasively,enhancing our understanding of central nervous system function and the mechanisms of plasticity in neurological disorders beyond traditional neurobiological methods.Evidence has shown that optogenetic modulation can enhance motor axon regeneration,achieve complete sensory reinnervation,and accelerate the recovery of neuromuscular function.This approach also induces complex patterns of coordinated motor neuron activity and promotes neural reorganization.Optogenetic approaches hold immense potential for therapeutic interventions in the central nervous system.They enable precise control of neural circuits and may offer new treatments for neurological disorders,particularly spinal cord injuries,peripheral nerve injuries,and other neurodegenerative diseases.
基金supported by Basic Research Programs of Science and Technology Commission Foundation of Shanxi Province,No.20210302123486(to WJ).
文摘Epilepsy,a common neurological disorder,is characterized by recurrent seizures that can lead to cognitive,psychological,and neurobiological consequences.The pathogenesis of epilepsy involves neuronal dysfunction at the molecular,cellular,and neural circuit levels.Abnormal molecular signaling pathways or dysfunction of specific cell types can lead to epilepsy by disrupting the normal functioning of neural circuits.The continuous emergence of new technologies and the rapid advancement of existing ones have facilitated the discovery and comprehensive understanding of the neural circuit mechanisms underlying epilepsy.Therefore,this review aims to investigate the current understanding of the neural circuit mechanisms in epilepsy based on various technologies,including electroencephalography,magnetic resonance imaging,optogenetics,chemogenetics,deep brain stimulation,and brain-computer interfaces.Additionally,this review discusses these mechanisms from three perspectives:structural,synaptic,and transmitter circuits.The findings reveal that the neural circuit mechanisms of epilepsy encompass information transmission among different structures,interactions within the same structure,and the maintenance of homeostasis at the cellular,synaptic,and neurotransmitter levels.These findings offer new insights for investigating the pathophysiological mechanisms of epilepsy and enhancing its clinical diagnosis and treatment.
基金supported by the National Key R&D Program of China,No.2023YFC2509700the Beijing Natural Science Foundation-Haidian Original Innovation Joint Fund,No.L232141the Research and Application of Clinical Characteristic Diagnosis and Treatment Program,No.Z221100007422019(all to WD)。
文摘Spinal cord injury is a severe neurological disorder;however,current treatment methods often fail to restore nerve function effectively.Spinal cord stimulation via electrical signals is a promising therapeutic modality for spinal cord injury.Based on similar principles,this review aims to explore the potential of optical and acoustic neuromodulation techniques,emphasizing their benefits in the context of spinal cord injury.Photoacoustic imaging,renowned for its noninvasive nature,high-resolution capabilities,and cost-effectiveness,is well recognized for its role in early diagnosis,dynamic monitoring,and surgical guidance in stem cell therapies for spinal cord injury.Moreover,photoacoustodynamic therapy offers multiple pathways for tissue regeneration.Optogenetics and sonogenetics use genetic engineering to achieve precise neuronal activation,while photoacoustoelectric therapy leverages photovoltaic materials for electrical modulation of the nervous system,introducing an innovative paradigm for nerve system disorder management.Collectively,these advancements represent a transformative shift in the diagnosis and treatment of spinal cord injury,with the potential to significantly enhance nerve function remodeling and improve patient outcomes.
基金supported by the National Key Research and Development Program of China(Nos.2021YFA1201302 and 2021YFA1201300)the National Natural Science Foundation of China(Nos.52303033,52173029)+1 种基金Shanghai Sailing Program(No.23YF1400400)the Natural Science Foundation of Shanghai(No.21ZR1400500).
文摘Optogenetic has been widely applied in various pathogenesis investigations of neuropathic diseases since its accurate and targeted regulation of neuronal activity.However,due to the mismatch between the soft tissues and the optical waveguide,the long-term neural regulation within soft tissue(such as brain and spinal cord)by implantable optical fibers is a large challenge.Herein,we designed a modulus selfadaptive hydrogel optical fiber(MSHOF)with tunable mechanical properties(Young’modulus was tunable in the range of 0.32-10.56MPa)and low light attenuation(0.12-0.21 dB/cm,472nm laser light),which adapts to light transmission under soft tissues.These advantages of MSHOF can ensure the effectiveness of optogenetic stimulation meanwhile safeguarding the safety of the brain/materials interaction interface.In addition,this work provides more design possibilities of MSHOF for photogenetic stimuli and has significant application prospects in photomedical therapy.
基金Australian National Health and Medical Research Council。
文摘In this study,we aimed to develop an in vivo electrophysiological bone-nerve preparation to record the activity of peripheral sensory neurons that innervate the murine tibia.A small nerve that innervates the tibial marrow cavity was identified in isoflurane-anesthetized C57BL/6 mice,and placed over a platinum hook electrode for extracellular recording.Whole-nerve activity was amplified,filtered and sampled at 20 kHz using PowerLab(ADInstruments).A cannula was placed into the marrow cavity to deliver mechanical stimuli(by pressurizing with injection of saline)and/or capsaicin.Optical stimulation was achieved by application of 473 nm blue light(1 Hz,0.25-0.5 ms,0-12.5 mW/mm)to the tibial marrow cavity in Wnt1-Cre;loxP-ChR2 mice.Murine bone afferent neurons responded to high threshold noxious mechanical stimulation,coded for the intensity of mechanical stimulation,could be sensitized by capsaicin,and did not suffer stimulus-evoked fatigue at 10-minute interstimulus intervals.Electrical and optical stimulation within the marrow cavity evoked action potentials with conduction velocities in the Aδand/or C fiber range.These new approaches to recording the activity of bone afferent neurons will allow us to take advantage of transgenic and optogenetic tools to further our understanding of mechanisms that generate and maintain bone pain in the future.
基金funded by the Natural Science Foundation of China(No.82305049).
文摘Depression is a multifaceted disorder with a largely unresolved etiology influenced by a complex interplay of pathogenic factors.Despite decades of research,it remains a major condition that significantly diminishes patients’quality of life.Advances in optogenetics have introduced a powerful tool for exploring the neural mechanisms underlying depression.By selectively expressing optogenes in specific cell types in mice,researchers can study the roles of these cells through targeted light stimulation,offering new insights into central nervous system disorders.The use of viral vectors to express opsins in distinct neuronal subtypes enables precise activation or inhibition of these neurons via light.When combined with behavioral,morphological,and electrophysiological analyses,optogenetics provides an invaluable approach to investigating the neural mechanisms of psychiatric conditions.This review synthesizes current research on the application of optogenetics to understand the mechanisms of depression.This study aims to enhance our knowledge of optogenetic strategies for regulating depression and advancing antidepressant research.
基金supported by the Beijing Natural Science Foundation of China under Grant 7222185。
文摘Objective:This study aims to establish an economically viable and easily accessible adult animal model for optogenetic activation of auditory neurons using adeno-associated viruses(AAVs)carrying Ch R2(H134R)to explore the potential of cochlear optogenetics as a hearing restoration technology.Methods:Healthy adult guinea pigs were used in the experiments.The viral vector AAV2/8-Ch R2(H134R)-h Syn-e YFP was administered to the right cochlea via the round window membrane.The confocal microscopy and reverse transcription polymerase chain reaction(RT-PCR)were utilized to analyze the Ch R2(H134R)expression localized to spiral ganglion neurons(SGNs).The auditory pathway activation was assessed by recording the optical compound action potential(oCAP)and acoustic compound action potential(a CAP)at various laser intensities.Results:The Ch R2(H134R)-e YFP expression was confirmed in 90%of the tested animals,localized to the SGNs of the injected ear.Higher m RNA levels of Ch R2(H134R)and e YFP were observed in the injected ear compared to the non-injected ear,while actin(Actb)m RNA levels were not significantly different.The o CAP was successfully elicited by a 470 nm blue light laser stimulus,with similar amplitudes and latency periods to those of a CAPs when the o CAP was evoked by 5.80 m W blue light and the a CAP was evoked by a 40 d B SPL click.The amplitudes of o CAPs increased with increasing laser intensity.Conclusion:This study demonstrates the viability of optogenetic activation of the auditory system in adult guinea pigs through the transduction of AAV-Ch R2(H134R)in SGNs.Cochlear optogenetics demonstrates potential as a hearing restoration technology,providing a basis for further clinical research and opening new avenues for investigation.
基金Supported by the Tianjin Municipal Education Commission Scientic Research Project No.2023YXZD10。
文摘The hippocampus is the brain structure that is responsible for the formation of learning memories.Sleep disorders leading to cognitive impairment are strongly associated with the hippocampus.Phototherapy offers a new physical therapy for the treatment of sleep disorders,with the advantages of being noninvasive and having few side effects.However,the mechanism by which phototherapy improves cognitive impairment caused by sleep disorders remains unclear.In this study,we used phototherapy combined with optogenetic technology to investigate the effect of noninvasive phototherapy on cognitive functions in sleep-deprived mice.Our results suggest that phototherapy might improve cognitive functions in sleep-deprived mice by modulating the hippocampus.Our study expands the research progress on noninvasive phototherapy for the treatment of sleep disorders.
文摘This study is based on wireless optogenetic technology,utilizing the CRY2/CIB1 photosensitive system to achieve spatiotemporal control of PD-L1 expression.In vitro experiments showed that the surface PD-L1 positivity rate of cells increased from 28.6±3.1%to 67.3±5.4%(P<0.001).In animal experiments,the terminal tumor volume in the light exposure group was 450±90 mm3,with a tumor inhibition rate of approximately 49.4%(P<0.001),and the median survival was extended to 32 days(compared to 24 days in the control group,P=0.004).Immunological tests revealed a significant increase in CD8+T cell infiltration(112±18 vs 52±10 cells/HPF,P<0.01),a 30%decrease in the proportion of Tregs(P<0.05),and an increase in the M1/M2 macrophage ratio to 1.8.The results suggest that the wireless optogenetic system can not only precisely regulate PD-L1 but also remodel the tumor immune microenvironment,providing a new approach for precise immunotherapy of GBM.
基金supported by the 2024 Key Technological Innovation and Industrialization Project of Fujian Province(Grant No.2024G021)the National Natural Science Foundation of China(Grant No.62274138)+3 种基金the Natural Science Foundation of Fujian Province of China(Grant No.2023J06012)the Science and Technology Plan Project in Fujian Province of China(Grant No.2021H0011)the Fundamental Research Funds for the Central Universities(Grant No.20720230029)the Compound Semiconductor Technology Collaborative Innovation Platform Project of FuXiaQuan National Independent Innovation Demonstration Zone(Grant No.3502ZCQXT2022005)。
文摘Micro-scaled light-emitting diode(LED)technology has emerged as a transformative tool in biomedical applications,offering innovative solutions across disease surveillance,treatment,and symptom rehabilitation.In disease surveillance,micro-scaled LEDs enable real-time,noninvasive monitoring of physiological parameters through wearable devices,such as skin-like health patches and wireless pulse oximeters;these systems leverage the miniaturization,low power consumption,and high precision of micro-scaled LEDs to track heart rate,blood oxygenation,and neural activity with exceptional accuracy.For disease treatment,micro-scaled LEDs play a pivotal role in optogenetic stimulation and phototherapy.By delivering specific light wavelengths,they enable precise cellular control for cardiac regeneration,neural modulation,and targeted cancer therapies,such as photodynamic therapy with reduced invasiveness.In addition,wireless micro-scaled LED systems facilitate localized and sustained treatments for conditions such as diabetic retinopathy.For symptom rehabilitation,micro-scaled LED-based devices enhance functional and aesthetic outcomes,exemplified by optical cochlear implants for high-resolution hearing restoration and flexible photostimulation patches for hair regrowth.The performance of micro-scale LEDs also brings new possibilities to the field of brain–computer interface.These applications highlight the versatility of micro-scaled LEDs in improving patient quality of life through minimally invasive,energy-efficient,and biocompatible solutions.Although there are still challenges in long-term stability and scalability,the integration of micro-scaled LEDs with advanced biomedical technologies promises to redefine personalized healthcare and therapeutic efficacy.
基金supported by grants from the Key Strategic Science and Technology Cooperation Project of the Ministry of Science and Technology of China(2023YFE0206800)the National Natural Science Foundation of China(81625006,31820103005,32200620,32170976,81971874)+1 种基金Zhejiang Province Natural Science Foundation of China(LZ24C090003 and LY21C090003)the Peak Discipline Cultivation Program of Zhejiang University School of Basic Medicine.
文摘Dear Editor,It is now well established that optogenetic stimulation can achieve precise intervention and modulate the activity of local neurons or neural circuits in the brain.Although this technique holds promise for clinical therapy for neurological and psychiatric disorders,it requires the expression of lightsensitive proteins(such as channel rhodopsin)or photoactivatable chemicals(such as caged neurotransmitters)in the targeted brain regions[1].
基金supported by the National Key Research and Development Program of China(2022YFE0201000)the National Natural Science Foundation of China(82174002,82104416,82204652)the High-Level University Development Program of Guangdong Province,and the Guangzhou Key Science and Technology Research and Development Project(202206010109)。
文摘Background:The development of ketamine-like rapid antidepressants holds promise for enhancing the therapeutic efficacy of depression,but the underlying cellular and molecular mechanisms remain unclear.Implicated in depression regulation,the neuropeptide pituitary adenylate cyclase-activating polypeptide(PACAP)is investigated here to examine its role in mediating the rapid antidepressant response.Methods:The onset of antidepressant response was assessed through depression-related behavioral paradigms.The signaling mechanism of PACAP in the hippocampal dentate gyrus(DG)was evaluated by utilizing site-directed gene knockdown,pharmacological interventions,or optogenetic manipulations.Overall,446 mice were used for behavioral and molecular signaling testing.Mice were divided into control or experimental groups randomly in each experiment,and the experimental manipulations included:chronic paroxetine treatments(4 d,9 d,14 d)or a single treatment of ketamine;social defeat or lipopolysaccharides-injection induced depression models;different doses of PACAP(0.4 ng/site,2 ng/site,4 ng/site;microinjected into the hippocampal DG);pharmacological intra-DG interventions(CALM and PACAP6-38);intra-DG viral-mediated PACAP RNAi;and opotogenetics using channelrhodopsins 2(ChR2)or endoplasmic natronomonas halorhodopsine 3.0(eNpHR3.0).Behavioral paradigms included novelty suppressed feeding test,tail suspension test,forced swimming test,and sucrose preference test.Western blotting,ELISA,or quantitative real-time PCR(RT-PCR)analysis were used to detect the expressions of proteins/peptides or genes in the hippocampus.Results:Chronic administration of the slow-onset antidepressant paroxetine resulted in an increase in hippocampal PACAP expression,and intra-DG blockade of PACAP attenuated the onset of the antidepressant response.The levels of hippocampal PACAP expression were reduced in both two distinct depression animal models and intra-DG knockdown of PACAP induced depression-like behaviors.Conversely,a single infusion of PACAP into the DG region produced a rapid and sustained antidepressant response in both normal and chronically stressed mice.Optogenetic intra-DG excitation of PACAP-expressing neurons instantly elicited antidepressant responses,while optogenetic inhibition induced depression-like behaviors.The longer optogenetic excitation/inhibition elicited the more sustained antidepressant/depression-like responses.Intra-DG PACAP infusion immediately facilitated the signaling for rapid antidepressant response by inhibiting calcium/calmodulin-dependent protein kinaseⅡ(CaM KⅡ)-eukaryotic elongation factor 2(eEF2)and activating the mammalian target of rapamycin(mTOR).Pre-activation of CaMKⅡsignaling within the DG blunted PACAP-induced rapid antidepressant response as well as eEF2-mTOR-brain-derived neurotrophic factor(BDNF)signaling.Finally,acute ketamine treatment upregulated hippocampal PACAP expression,whereas intraDG blockade of PACAP signaling attenuated ketamine’s rapid antidepressant response.Conclusions:Activation of hippocampal PACAP signaling induces a rapid antidepressant response through the regulation of CaMKⅡinhibition-governed eEF2-mTOR-BDNF signaling.
文摘The basal ganglia(BG) act as a cohesive functional unit that regulates motor function,habit formation,and reward/addictive behaviors. However,it is still not well understood how the BG maintains wakefulness and suppresses sleep to achieve al these fundamental functions until genetical y engineered systems developed these years. Significant research efforts have recently been directed at developing genetic-molecular tools to achieve reversible and cell-type specific in vivo silencing or activation of neurons in behaving animals. Optogenetic tools can be used both to specifically activate or inhibit neurons of interest and identify functional synaptic connectivity between specific neuronal populations,both in vivo and in brain slices. Another recently developed system by Roth and colleagues permits the selective and ″remote″ manipulation(activation and silencing) of neuronal activity via all 3 major GPCR signaling pathways(G_i,G_s and G_q). These so-called ″ designer receptors exclusively activated by designer drugs″(DREADD) involve mutant GPCRs that do not respond to their endogenous ligands but are responsive to otherwise inert biological compounds. Recently,we demonstrated the essential roles and the neural pathways of the neurons expressing adenosine A_(2A) receptors or dopamine D_1 receptors in the BG for sleep-wake regulation using the genetically engineered systems including optogenetics and DREADD. We proposed a plausible model in which the caudate-putamen and the nucleus accumbens integrates behavioral processes with sleep/wakefulness through adenosine and dopamine receptors.
基金supported by the Strategic Priority Research Program of the Chinese Academy of Sciences, China (XDB02030005)
文摘Many complex behaviors that do not require learning are displayed and are termed innate. Although traditionally the subject matter of ethology, innate behaviors offer a unique entry point for neuroscientists to dissect the physiological mechanisms governing complex behaviors. Since the last century, converging evidence has implicated the hypothalamus as the central brain area that controls innate behaviors. Recent studies using cutting-edge tools have revealed that genetically-defined populations of neurons residing in distinct hypothalamic nuclei and their associated neural pathways regulate the initiation and maintenance of diverse behaviors including feeding, sleep, aggression, and parental care. Here, we review the newly-defined hypothalamic pathways that regulate each innate behavior. In addition, emerging general principles of the neural control of complex behaviors are discussed.
基金supported by grants from the National Natural Science Foundation of China (31771167 and 31571090)the National Basic Research Development Program of China (2016YFC1306700)+1 种基金the Non-profit Central Research Institute Fund of the Chinese Academy of Medical Sciences (2018PT31041)the Fundamental Research Funds for the Central Universities of China (2017FZA7003)
文摘Although extensively studied, the exact role of sleep in learning and memory is still not very clear. Sleep deprivation has been most frequently used to explore the effects of sleep on learning and memory, but the results from such studies are inevitably complicated by concurrent stress and distress. Furthermore, it is not clear whether there is a strict time-window between sleep and memory consolidation. In the present study we were able to induce time-locked slow-wave sleep(SWS) in mice by optogenetically stimulating GABAergic neurons in the parafacial zone(PZ), providing a direct approach to analyze the influences of SWS on learning and memory with precise time-windows. We found that SWS induced by light for 30 min immediately or 15 min after the training phase of the object-in-place task significantly prolonged the memory from 30 min to 6 h. However, induction of SWS 30 min after the training phase did not improve memory, suggesting a critical time-window between the induction of a brief episode of SWS and learning for memory consolidation.Application of a gentle touch to the mice during light stimulation to prevent SWS induction also failed to improve memory, indicating the specific role of SWS,but not the activation of PZ GABAergic neurons itself, in memory consolidation. Similar influences of light-induced SWS on memory consolidation also occurred for Y-maze spatial memory and contextual fear memory, but not for cued fear memory. SWS induction immediately before the test phase had no effect on memory performance, indicating that SWS does not affect memory retrieval. Thus, by induction of a brief-episode SWS we have revealed a critical time window for the consolidation of hippocampusdependent memory.
基金Grants from the Natural Science Foundation of China(31730035,82071219,91632305,and 91949205)the Ministry of Science and Technology of China(2016YFC1305800)the Guangdong Provincial Key S&T Program(2018B030336001).
文摘Alzheimer’s disease(AD)is the most common neurodegenerative disorder and there is currently no cure.Neural circuit dysfunction is the fundamental mechanism underlying the learning and memory deficits in patients with AD.Therefore,it is important to understand the structural features and mechanisms underlying the deregulated circuits during AD progression,by which new tools for intervention can be developed.Here,we briefly summarize the most recently established cutting-edge experimental approaches and key techniques that enable neural circuit tracing and manipulation of their activity.We also discuss the advantages and limitations of these approaches.Finally,we review the applications of these techniques in the discovery of circuit mechanisms underlyingβ-amyloid and tau pathologies during AD progression,and as well as the strategies for targeted AD treatments.
基金Project supported by the Fonds de recherche du Québec-Nature et technologies(FRQNT)Canada for Merit Scholarship Program for Foreign Students(PBEEE)Fellowship。
文摘Ion channels present in the plasma membrane are responsible for integration and propagation of electric signals,which transmit information in nerve cells.Malfunction of these ion channels leads to many neurological diseases.Recently,optogenetic technology has gained a lot of attention for the manipulation of neuronal circuits.Optogenetics is a neuromodulation approach that has been developed to control neuronal functions and activities using light.The lanthanide-doped upconversion nanoparticles(UCNPs)absorb low energy photons in near-infrared(NIR) window and emit high energy photons in the visible spectrum region via nonlinear processes.In the last few decades,UCNPs have gained great attention in various bio-medical applications such as bio-imaging,drug delivery and optogenetics.The near-infrared illumination is considered more suitable for optogenetics application,due to its lower degree of light attenuation and higher tissue penetration compared to visible light.Therefore,UCNPs have been considered as the new promising candidates for optogenetics applications.Upconversion nanoparticlemediated optogenetic systems provide a great opportunity to manipulate the ion channel in deep tissue.Herein,we summarize the upconversion photoluminescence in lanthanide doped nanomaterials and its mechanisms and several approaches adopted to tune emission color or enhance upconversion efficiency.Recent advances of lanthanide-doped UCNPs design strategy and their mechanism are reviewed.Then,we discuss the neural circuitry modulation using upconversion nanoparticles mediated optogenetics.Moreover,the future perspectives towards optogenetics are also included.
基金supported by grants from the National Natural Science Foundation of China(82073819 and 81872843)Fundamental Research Funds for the Central Universities of China(2021QNA7005).
文摘Pain is an unpleasant sensory and emotional experience associated with,or resembling that associated with,actual or potential tissue damage.The processing of pain involves complicated modulation at the levels of the periphery,spinal cord,and brain.The pathogenesis of chronic pain is still not fully understood,which makes the clinical treatment challenging.Optogenetics,which combines optical and genetic technologies,can precisely intervene in the activity of specific groups of neurons and elements of the related circuits.Taking advantage of optogenetics,researchers have achieved a body of new findings that shed light on the cellular and circuit mechanisms of pain transmission,pain modulation,and chronic pain both in the periphery and the central nervous system.In this review,we summarize recent findings in pain research using optogenetic approaches and discuss their significance in understanding the pathogenesis of chronic pain.
