In vivo fiber photometry of neural activity in response to optogenetically manipulated inputs in freely moving mice

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.

Influences of NR2B-containing NMDA Receptors Knockdown on Neural Activity in Hippocampal Newborn Neurons

Summary： Adult-bom neurons undergo a transient period of plasticity during their integration into the neural circuit. This transient plasticity may involve NMDA receptors containing NR2B, the major sub unit expressed at early developmental stages. The main objective of the present study was to investigate the effects of NR2B gene knockdown on the functional integration of the adult-born granule cells gen- erated from the subgranule zone （SGZ） in the hippocampus. The small interfering RNA （siRNA） was used to knock down the NR2B gene in the adult-born hippocampal neurons. In the functional integration test, the mice were exposed to a novel environment （open field arena）, and the expression of c-fos was immunohistochemically detected in the hippocampus. After exposure to the novel environment, siRNA-NR2B mice were significantly different from control mice in either the number of squares or the number of rears they crossed, showing decreased horizontal and vertical activity （P〈0.05）. Moreover, the c-fos expression was increased in both control and siRNA-NR2B mice after open field test. But, it was significantly lower in siRNA-NR2B neurons than in control neurons. It was concluded that the neu- ral activity of newborn neurons is regulated by their own NR2B-containing NMDA glutamate receptors during a short, critical period after neuronal birth.

Research on the Relationship Between Learning Motivation and Neural Activity in the Learning Process of Instructional Video:A NIRS Study

As the intrinsic driving force to promote learner’s learning,learning motivation is one of the key factors that affect learning engagement and efficiency.In terms of optimizing instructional videos and strengthening learning effects,it is particularly important to understand the cognitive neural mechanism and influencing factors of the changes of learning motivation.By using the near-infrared spectrometer technology,the paper has collected the state of neural activity while learners were learning different instructional videos,and has analyzed the relationship between the learning motivation of instructional videos and the state of neural activity in the learning process from the angle of cognitive neuroscience.It is found that both the intrinsic and extrinsic learning motivation of instructional videos will affect the state of neural activity in the learning process;the learning process will also affect the intensity of learning motivation,while the preparation of fine instructional videos will also cause the transfer of learning motivation.

Retinal ganglion cells regenerate long-distance axons through neural activity stimulation and find their way back to the brain

Human central nerve system(CNS)is an extremely complex and delicate structure.While regeneration is possible in some reptiles and fish CNS,the regeneration capacity seems completely lost in adult mammals.Therefore,the classic concept is that once neurons in mammal

Correlation between primary motor cortex neural activity and fingertip force following transcranial magnetic stimulation

A better understanding of the neural mechanisms of finger-force regulation can help to explain the relationship between the central nervous system and nerve-muscle force, as well as assist in motor functional rehabilitation and the development robot hand designs. In the present study, 11 healthy volunteers performed a different target force-tracking task, which involved the index finger alone, index and middle finger together, and the combination of four fingers （i.e., index, middle, ring, and little）. The target force trace corresponded to 3 levels of 20% maximal voluntary changes （MVC）, 30% MVC, and 40% MVC in 20 seconds. In the test, an unexpected single 120% motor threshold transcranial magnetic stimulation was applied to the primary motor cortex （M1） during force tracking. Results revealed that peak force changes increased with increasing background force and the number of involved task fingers. These results demonstrate that M1 neural activities correlate with finger-force production, and M1 plays a role in finger-force control. Moreover, different neuronal networks were required for different finger patterns; a complicated task required multi-finger combinations and a complicated neuronal network comprised a large number of neurons.

Genetically encoded neural activity indicators

Recent years have witnessed the fascinating development of imaging approaches to studying neural activities; this progress has been based on an influx of ideas and methods from molecular biology and optical engineering. Here we review the design and application of genetically encoded indicators for calcium ions, membrane potential and neurotransmitters. We also summarize common strategies for the design and optimization of genetically encoded neural activity indicators.

Towards high-density recording of brain-wide neural activity

Brain activity is highly structured within local microcircuits and brain-wide networks,involving exquisite coordination across multiple brain regions in both superficial and deep structures^([1]).To understand how brain represents,transforms and communicates in-

Topological probability and connection strength induced activity in complex neural networks

Recent experimental evidence suggests that some brain activities can be assigned to small-world networks. In this work, we investigate how the topological probability p and connection strength C affect the activities of discrete neural networks with small-world （SW） connections. Network elements are described by two-dimensional map neurons （2DMNs） with the values of parameters at which no activity occurs. It is found that when the value of p is smaller or larger, there are no active neurons in the network, no matter what the value of connection strength is; for a given appropriate connection strength, there is an intermediate range of topological probability where the activity of 2DMN network is induced and enhanced. On the other hand, for a given intermediate topological probability level, there exists an optimal value of connection strength such that the frequency of activity reaches its maximum. The possible mechanism behind the action of topological probability and connection strength is addressed based on the bifurcation method. Furthermore, the effects of noise and transmission delay on the activity of neural network are also studied.

INTRINSIC OPTICAL SIGNAL IMAGING OF RETINAL ACTIVITY IN FROG EYE

Using a near-infrared(NIR)light flood-illumination imager equipped with a high-speed(120 Hz)CCD camera,we demonstrated optical imaging of stimulus-evoked retinal activity in isolated,but intact,frog eye.Both fast and slow transient intrinsic optical signals(IOSs)were observed.Fast optical response occurred immediately after the stimulus onset,could reach peak magnitude within 100 ms,and correlated tightly with ON and OFF edges of the visible light stimulus;while slow optical response lasted a relatively long time(many seconds).High-resolution images revealed both positive(increasing)and negative(decreasing)IOSs,and dynamic optical change at individual CCD pixels could often exceed 10%of the background light intensity.Our experiment on isolated eye suggests that further development of fast,high(sub-cellular)resolution fundus imager will allow robust detection of fast IOSs in vivo,and thus allow noninvasive,three-dimensional evaluation of retinal neural function.

Simulation Study of the Dendritic Effect on Direct MRI Detection of Neural Electric Event

Currently hemodynamic-based functional MRI technique is of limitation in temporal resolution. As neural activities in the brain accompany with current induced neuronal magnetic fields （NMF）, it is possible to utilize MRI to detect NMF directly thus to improve the temporal resolution. In this work, the contribution of dendrite branch to NMF is investigated by numeric simulation. The results indicate that the existence of dendrite branch may enhance the detectability of NMF by MRI directly.

Closed-loop control of epileptiform activities in a neural population model using a proportional-derivative controller

Epilepsy is believed to be caused by a lack of balance between excitation and inhibitation in the brain. A promising strategy for the control of the disease is closed-loop brain stimulation. How to determine the stimulation control parameters for effective and safe treatment protocols remains, however, an unsolved question. To constrain the complex dynamics of the biological brain, we use a neural population model（NPM）. We propose that a proportional-derivative（PD） type closed-loop control can successfully suppress epileptiform activities. First, we determine the stability of root loci, which reveals that the dynamical mechanism underlying epilepsy in the NPM is the loss of homeostatic control caused by the lack of balance between excitation and inhibition. Then, we design a PD type closed-loop controller to stabilize the unstable NPM such that the homeostatic equilibriums are maintained; we show that epileptiform activities are successfully suppressed. A graphical approach is employed to determine the stabilizing region of the PD controller in the parameter space, providing a theoretical guideline for the selection of the PD control parameters. Furthermore, we establish the relationship between the control parameters and the model parameters in the form of stabilizing regions to help understand the mechanism of suppressing epileptiform activities in the NPM. Simulations show that the PD-type closed-loop control strategy can effectively suppress epileptiform activities in the NPM.

Neural network prediction of solar cycle 24

The ability to predict the future behavior of solar activity has become extremely import due to its effect on the environment near the Earth. Predictions of both the amplitude and timing of the next solar cycle will assist in estimating the various consequences of space weather. The level of solar activity is usually expressed by in- ternational sunspot number （Rz）. Several prediction techniques have been applied and have achieved varying degrees of success in the domain of solar activity prediction. We predict a solar index （Rz） in solar cycle 24 by using a neural network method. The neural network technique is used to analyze the time series of solar activity. According to our predictions of yearly sunspot number, the maximum of cycle 24 will occur in the year 2013 and will have an annual mean sunspot number of 65. Finally, we discuss our results in order to compare them with other suggested predictions.

Neural activation while perceiving biological motion in dynamic facial expressions and point-light body action animations

BACKGROUND： The interpretation of non-verbal social signals relies heavily on the ability to perceive biological motion. The posterior superior temporal sulcus is an important part of a network involved in biological motion processing. However, the underlying functional organization remains poorly understood. Several studies have suggested topographical representation of motion from different body parts within this region. However, other studies have shown that the posterior superior temporal sulcus responds equally to any body part. OBJECTIVE： Through the use of functional magnetic resonance imaging, the effects of socially relevant biological motion stimuli to activate a specific cortical area within posterior superior temporal sulcus, even if different body parts are involved in motion, will be analyzed. DESIGN, TIME AND SETTING： A functional magnetic resonance imaging, block-design was performed at the Magnetic Resonance Imaging, Surgical Medical Investigation Center, Havana, Cuba between 2004 and 2005. PARTICIPANTS： Thirteen healthy volunteers, from 19 to 55 years of age and compris!ng eight males and five females, were included in the study. METHODS： A conjunction analysis of responses to natural, dynamic, fearful, facial expressions and point-light, body-motion animations. MAIN OUTCOME MEASURES： The corresponding functionally specialized areas, as well as neural areas significant for both types of stimuli, were identified. RESULTS： One region within the posterior superior temporal sulcus of the right hemisphere was equally activated by facial and body complex motion. CONCLUSION： A site of common neural activity existed within the posterior superior temporal sulcus, which was not specific to a biological motion type. In addition, the activity was not related to a topographically organized body-part map, which suggested high-level visual representation of biological motion in this region.

A rabies virus-based toolkit for efficient retrograde labeling and monosynaptic tracing

Analyzing the structure and function of the brain's neural network is critical for identifying the working principles of the brain and the mechanisms of brain diseases.Recombinant rabies viral vectors allow for the retrograde labeling of projection neurons and cell type-specific trans-monosynaptic tracing,making these vectors powerful candidates for the dissection of synaptic inputs.Although several attenuated rabies viral vectors have been developed,their application in studies of functional networks is hindered by the long preparation cycle and low yield of these vectors.To overcome these limitations,we developed an improved production system for the rapid rescue and preparation of a high-titer CVS-N2c-ΔG virus.Our results showed that the new CVS-N2c-ΔG-based toolkit performed remarkably:(1)N2cG-coated CVS-N2c-ΔG allowed for efficient retrograde access to projection neurons that were unaddressed by rAAV9-Retro,and the efficiency was six times higher than that of rAAV9-Retro;(2)the trans-monosynaptic efficiency of oG-mediated CVS-N2c-ΔG was 2–3 times higher than that of oG-mediated SAD-B19-ΔG;(3)CVS-N2c-ΔG could delivery modified genes for neural activity monitoring,and the time window during which this was maintained was 3 weeks;and(4)CVS-N2c-ΔG could express sufficient recombinases for efficient transgene recombination.These findings demonstrate that new CVS-N2c-ΔG-based toolkit may serve as a versatile tool for structural and functional studies of neural circuits.

Multistability of delayed complex-valued recurrent neural networks with discontinuous real-imaginarytype activation functions

In this paper, the multistability issue is discussed for delayed complex-valued recurrent neural networks with discontinuous real-imaginary-type activation functions. Based on a fixed theorem and stability definition, sufficient criteria are established for the existence and stability of multiple equilibria of complex-valued recurrent neural networks. The number of stable equilibria is larger than that of real-valued recurrent neural networks, which can be used to achieve high-capacity associative memories. One numerical example is provided to show the effectiveness and superiority of the presented results.

In Silico Investigation of Agonist Activity of a Structurally Diverse Set of Drugs to hPXR Using HM-BSM and HM-PNN

The human pregnane X receptor（hPXR） plays a critical role in the metabolism, transport and clearance of xenobiotics in the liver and intestine. The hPXR can be activated by a structurally diverse of drugs to initiate clinically relevant drug-drug interactions. In this article, in silico investigation was performed on a structurally diverse set of drugs to identify critical structural features greatly related to their agonist activity towards h PXR. Heuristic method（HM）-Best Subset Modeling（BSM） and HM-Polynomial Neural Networks（PNN） were utilized to develop the linear and non-linear quantitative structure-activity relationship models. The applicability domain（AD） of the models was assessed by Williams plot. Statistically reliable models with good predictive power and explain were achieved（for HM-BSM, r^2=0.881, q^2_（LOO）=0.797, q^2_（EXT）=0.674; for HM-PNN, r^2=0.882, q^2_（LOO）=0.856, q^2_（EXT）=0.655）. The developed models indicated that molecular aromatic and electric property, molecular weight and complexity may govern agonist activity of a structurally diverse set of drugs to h PXR.

Epidural electrical stimulation for spinal cord injury

A long-standing goal of spinal cord injury research is to develop effective repair strategies,which can restore motor and sensory functions to near-normal levels.Recent advances in clinical management of spinal cord injury have significantly improved the prognosis,survival rate and quality of life in patients with spinal cord injury.In addition,a significant progress in basic science research has unraveled the underlying cellular and molecular events of spinal cord injury.Such efforts enabled the development of pharmacologic agents,biomaterials and stem-cell based therapy.Despite these efforts,there is still no standard care to regenerate axons or restore function of silent axons in the injured spinal cord.These challenges led to an increased focus on another therapeutic approach,namely neuromodulation.In multiple animal models of spinal cord injury,epidural electrical stimulation of the spinal cord has demonstrated a recovery of motor function.Emerging evidence regarding the efficacy of epidural electrical stimulation has further expanded the potential of epidural electrical stimulation for treating patients with spinal cord injury.However,most clinical studies were conducted on a very small number of patients with a wide range of spinal cord injury.Thus,subsequent studies are essential to evaluate the therapeutic potential of epidural electrical stimulation for spinal cord injury and to optimize stimulation parameters.Here,we discuss cellular and molecular events that continue to damage the injured spinal cord and impede neurological recovery following spinal cord injury.We also discuss and summarize the animal and human studies that evaluated epidural electrical stimulation in spinal cord injury.

Brief electrical nerve stimulation enhances intrinsic repair capacity of the focally demyelinated central nervous system

Our lab has shown that brief electrical nerve stimulation(ES)has a dramatic impact on remyelination of lysophosphatidyl choline(LPC)-induced focally demyelinated rat peripheral nerves,while also inducing an axon-protective phenotype and shifting macrophages from a predominantly pro-inflammatory toward a pro-repair phenotype.Whether this same potential exists in the central nervous system is not known.Thus,for proof of principle studies,the peripheral nerve demyelination and ES model was adapted to the central nervous system,whereby a unilateral focal LPC-induced demyelination of the dorsal column at the lumbar enlargement where the sciatic nerve afferents enter was created,so that subsequent ipsilateral sciatic nerve ES results in increased neural activity in the demyelinated axons.Data reveal a robust focal demyelination at 7 days post-LPC injection.Delivery of 1-hour ES at 7 days post-LPC polarizes macrophages/microglia toward a pro-repair phenotype when examined at 14 days post-LPC;results in smaller LPC-associated regions of inflammation compared to non-stimulated controls;results in significantly more cells of the oligodendroglial lineage in the demyelinated region;elevates myelin basic protein levels;and shifts the paranodal protein Caspr along demyelinated axons to a more restricted distribution,consistent with reformation of the paranodes of the nodes of Ranvier.ES also significantly enhanced levels of phosphorylated neurofilaments detected in the zones of demyelination,which has been shown to confer axon protection.Collectively these findings support that strategies that increase neural activity,such as brief electrical stimulation,can be beneficial for promoting intrinsic repair following focal demyelinating insults in demyelinating diseases such as multiple sclerosis.All animal procedures performed were approved by the University of Saskatchewan's Animal Research Ethics Board(protocol#20090087;last approval date:November 5,2020).

Axonal remodeling in the corticospinal tract after stroke： how does rehabilitative training modulate it？

Stroke causes long-term disability, and rehabilitative training is commonly used to improve the consecutive functional recovery. Following brain damage, surviving neurons undergo morphological alterations to reconstruct the remaining neural network. In the motor system, such neural network remodeling is observed as a motor map reorganization. Because of its significant correlation with functional recovery, motor map reorganization has been regarded as a key phenomenon for functional recovery after stroke. Although the mechanism underlying motor map reorganization remains unclear, increasing evidence has shown a critical role for axonal remodeling in the corticospinal tract. In this study, we review previous studies investigating axonal remodeling in the corticospinal tract after stroke and discuss which mechanisms may underlie the stimulatory effect of rehabilitative training. Axonal remodeling in the corticospinal tract can be classified into three types based on the location and the original targets of corticospinal neurons, and it seems that all the surviving corticospinal neurons in both ipsilesional and contralesional hemisphere can participate in axonal remodeling and motor map reorganization. Through axonal remodeling, corticospinal neurons alter their output selectivity from a single to multiple areas to compensate for the lost function. The remodeling of the corticospinal axon is influenced by the extent of tissue destruction and promoted by various therapeutic interventions, including rehabilitative training. Although the precise molecular mechanism underlying rehabilitation-promoted axonal remodeling remains elusive, previous data suggest that rehabilitative training promotes axonal remodeling by upregulating growth-promoting and downregulating growth-inhibiting signals.

Therapeutic potential of neuromodulation for demyelinating diseases

Neuromodulation represents a cutting edge class of both invasive and non-invasive therapeutic methods which alter the activity of neurons.Currently,several different techniques have been developed-or are currently being investigated–to treat a wide variety of neurological and neuropsychiatric disorders.Recently,in vivo and in vitro studies have revealed that neuromodulation can also induce myelination,meaning that it could hold potential as a therapy for various demyelinating diseases including multiple sclerosis and progressive multifocal leukencepalopathy.These findings come on the heels of a paradigm shift in the view of myelin's role within the nervous system from a static structure to an active co-regulator of central nervous system plasticity and participant in neuron-mediated modulation.In the present review,we highlight several of the recent findings regarding the role of neural activity in altering myelination including several soluble and contact-dependent factors that seem to mediate neural activitydependent myelination.We also highlight several considerations for neuromodulatory techniques,including the need for further research into spatiotemporal precision,dosage,and the safety and efficacy of transcranial focused ultrasound stimulation,an emerging neuromodulation technology.As the field of neuromodulation continues to evolve,it could potentially bring forth methods for the treatment of demyelinating diseases,and as such,further investigation into the mechanisms of neuron-dependent myelination as well as neuro-imaging modalities that can monitor myelination activity is warranted.