Diffusive field coupling-induced synchronization between neural circuits under energy balance

When charged bodies come up close to each other,the field energy is diffused and their states are regulated under bidirectional field coupling.For biological neurons,the diversity in intrinsic electric and magnetic field energy can create synaptic connection for fast energy balance and synaptic current is passed across the synapse channel;as a result,energy is pumped and exchanged to induce synchronous firing modes.In this paper,a capacitor is used to connect two neural circuits and energy propagation is activated along the coupling channel.The intrinsic field energy in the two neural circuits is exchanged and the coupling intensity is controlled adaptively using the Heaviside function.Some field energy is saved in the coupling channel and is then sent back to the coupled neural circuits to reach energy balance.Therefore the circuits can reach possible energy balance and complete synchronization.It is possible that the diffusive energy of the coupled neurons inspires the synaptic connections to grow stronger for possible energy balance.

Imaging changes in neural circuits in patients with depression using 1 H-magnetic resonance spectroscopy and diffusion tensor imaging

1 H-magnetic resonance spectroscopy imaging and diffusion tensor imaging were performed in 19 patients with mild depression and in 13 controls.The mean age of the patients was 31 years.The mean Hamilton depression score of the patients was 22.5±13.2.N-acetylaspartate,choline and creatine concentrations and the average diffusion coefficient and fractional anisotropy values were measured in the bilateral hippocampus,striatum,thalamus and prefrontal deep white matter. Compared with the control group,the mild depressed patients had：（1）a higher choline/creatine ratio and a negative correlation between the choline/creatine ratio and the average diffusion coefficient in the hippocampus;（2）a lower choline/creatine ratio and a higher fractional anisotropy in the striatum;（3）a lower fractional anisotropy and a positive correlation between the fractional anisotropy and the choline/creatine ratio in the prefrontal deep white matter;and（4）a higher average diffusion coefficient and a positive correlation between the choline/creatine ratio and the N-acetylaspartate/creatine ratio in the thalamus,as well as positive correlation between the choline/creatine ratio and Hamilton depression scores.These data suggest evidence of abnormal connectivity in neurofibrotic microstructures and abnormal metabolic alterations in the limbic-cortical-striatal-pallidal-thalamic neural circuit in patients with mild depression.

Genetic Approaches for Neural Circuits Dissection in Non-human Primates

Genetic tools,which can be used for the morphology study of specific neurons,pathway-selective connectome mapping,neuronal activity monitoring,and manipulation with a spatiotemporal resolution,have been widely applied to the understanding of complex neural circuit formation,interactions,and functions in rodents.Recently,similar genetic approaches have been tried in non-human primates(NHPs)in neuroscience studies for dissecting the neural circuits involved in sophisticated behaviors and clinical brain disorders,although they are still very preliminary.In this review,we introduce the progress made in the development and application of genetic tools for brain studies on NHPs.We also discuss the advantages and limitations of each approach and provide a perspective for using genetic tools to study the neural circuits of NHPs.

Neural circuits and temporal plasticity in hindlimb representation of rat primary somatosensory cortex:revisited by multi-electrode array on brain slices

Objective The well-established planar multi-electrode array recording technique was used to investigate neural circuits and temporal plasticity in the hindlimb representation of the rat primary somatosensory cortex （S1 area） . Methods Freshly dissociated acute brain slices of rats were subject to constant perfusion with oxygenated artificial cerebrospinal fluid （95% O2 and 5% CO2） , and were mounted on a Med64 probe （64 electrodes, 8×8 array） for simultaneous multi-site electrophysiological recordings. Current sources and sinks across all the 64 electrodes were transformed into two-dimensional current source density images by bilinear interpolation at each point of the 64 electrodes. Results The local intracortical connection, which is involved in mediation of downward information flow across layers II-VI, was identified by electrical stimulation （ES） at layers II-III. The thalamocortical connection, which is mainly involved in mediation of upward information flow across layers II-IV, was also characterized by ES at layer IV. The thalamocortical afferent projections were likely to make more synaptic contacts with S1 neurons than the intracortical connections did. Moreover, the S1 area was shown to be more easily activated and more intensively innervated by the thalamocortical afferent projections than by the intracortical connections. Finally, bursting conditioning stimulus （CS） applied within layer IV of the S1 area could success-fully induce long-term potentiation （LTP） in 5 of the 6 slices （83.3%） , while the same CS application at layers II-III induced no LTP in any of the 6 tested slices. Conclusion The rat hindlimb representation of S1 area is likely to have at least 2 patterns of neural circuits on brain slices： one is the intracortical circuit （ICC） formed by interlaminar connections from layers II-III, and the other is the thalamocortical circuit （TCC） mediated by afferent connections from layer IV. Besides, ICC of the S1 area is spatially limited, with less plasticity, while TCC is spatially extensive and exhibits a better plasticity in response to somatosensory afferent stimulation. The present data provide a useful experimental model for further studying microcircuit properties in S1 cortex at the network level in vitro.

Grand Research Plan for Neural Circuits of Emotion and Memory-Current status of neural circuit studies in China

During recent years, major advances have been made in neuroscience, i.e., asynchronous release, three-dimensional structural data sets, saliency maps, magnesium in brain research, and new functional roles of long non-coding RNAs. Especially, the development of optogenetic technology provides access to important information about relevant neural circuits by allowing the activation of specific neurons in awake mammals and directly observing the resulting behavior. The Grand Research Plan for Neural Circuits of Emotion and Memory was launched by the National Natural Science Foundation of China. It takes emotion and memory as its main objects, making the best use of cutting-edge technologies from medical science, life science and information science. In this paper, we outline the current status of neural circuit studies in China and the technologies and methodologies being applied, as well as studies related to the impairments of emotion and memory. In this phase, we are making efforts to repair the current deficiencies by making adjustments, mainly involving four aspects of core scientific issues to investigate these circuits at multiple levels. Five research directions have been taken to solve important scientific problems while the Grand Research Plan is implemented. Future research into this area will be multimodal, incorporating a range of methods and sciences into each project. Addressing these issues will ensure a bright future, major discoveries, and a higher level of treatment for all affected by debilitating brain illnesses.

Illuminating Neural Circuits in Alzheimer’s Disease

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.

Recent Advances in the Genetic Dissection of Neural Circuits in Drosophila

Nervous systems endow animals with cognition and behavior. To understand how nervous systems control behavior, neural circuits mediating distinct functions need to be identified and characterized. With superior genetic manipulability, Drosophila is a model organism at the leading edge of neural circuit analysis. We briefly introduce the state-of-the-art genetic tools that permit precise labeling of neurons and their interconnectivity and investigating what is happening in the brain of a behaving animal and manipulating neurons to determine how behaviors are affected. Brain-wide wiring diagrams, created by light and electron microscopy, bring neural circuit analysis to a new level and scale. Studies enabled by these tools advances our understanding of the nervous system in relation to cognition and behavior.

Lighting Up Neural Circuits by Viral Tracing

Neurons are highly interwoven to form intricate neural circuits that underlie the diverse functions of the brain.Dissecting the anatomical organization of neural circuits is key to deciphering how the brain processes information,produces thoughts,and instructs behaviors.Over the past decades,recombinant viral vectors have become the most commonly used tracing tools to define circuit architecture.In this review,we introduce the current categories of viral tools and their proper application in circuit tracing.We further discuss some advances in viral tracing strategy and prospective innovations of viral tools for future study.

Functional near-infrared spectroscopy in non-invasive neuromodulation

Non-invasive cerebral neuromodulation technologies are essential for the reorganization of cerebral neural networks,which have been widely applied in the field of central neurological diseases,such as stroke,Parkinson’s disease,and mental disorders.Although significant advances have been made in neuromodulation technologies,the identification of optimal neurostimulation paramete rs including the co rtical target,duration,and inhibition or excitation pattern is still limited due to the lack of guidance for neural circuits.Moreove r,the neural mechanism unde rlying neuromodulation for improved behavioral performance remains poorly understood.Recently,advancements in neuroimaging have provided insight into neuromodulation techniques.Functional near-infrared spectroscopy,as a novel non-invasive optical brain imaging method,can detect brain activity by measuring cerebral hemodynamics with the advantages of portability,high motion tole rance,and anti-electromagnetic interference.Coupling functional near-infra red spectroscopy with neuromodulation technologies offe rs an opportunity to monitor the cortical response,provide realtime feedbac k,and establish a closed-loop strategy integrating evaluation,feedbac k,and intervention for neurostimulation,which provides a theoretical basis for development of individualized precise neuro rehabilitation.We aimed to summarize the advantages of functional near-infra red spectroscopy and provide an ove rview of the current research on functional near-infrared spectroscopy in transcranial magnetic stimulation,transcranial electrical stimulation,neurofeedback,and braincomputer interfaces.Furthermore,the future perspectives and directions for the application of functional near-infrared spectroscopy in neuromodulation are summarized.In conclusion,functional near-infrared spectroscopy combined with neuromodulation may promote the optimization of central pellral reorganization to achieve better functional recovery form central nervous system diseases.

Role of the globus pallidus in motor and non-motor symptoms of Parkinson's disease

The globus pallidus plays a pivotal role in the basal ganglia circuit. Parkinson's disease is characterized by degeneration of dopamine-producing cells in the substantia nigra, which leads to dopamine deficiency in the brain that subsequently manifests as various motor and non-motor symptoms. This review aims to summarize the involvement of the globus pallidus in both motor and non-motor manifestations of Parkinson's disease. The firing activities of parvalbumin neurons in the medial globus pallidus, including both the firing rate and pattern, exhibit strong correlations with the bradykinesia and rigidity associated with Parkinson's disease. Increased beta oscillations, which are highly correlated with bradykinesia and rigidity, are regulated by the lateral globus pallidus. Furthermore,bradykinesia and rigidity are strongly linked to the loss of dopaminergic projections within the cortical-basal ganglia-thalamocortical loop. Resting tremors are attributed to the transmission of pathological signals from the basal ganglia through the motor cortex to the cerebellum-ventral intermediate nucleus circuit. The cortico–striato–pallidal loop is responsible for mediating pallidi-associated sleep disorders. Medication and deep brain stimulation are the primary therapeutic strategies addressing the globus pallidus in Parkinson's disease. Medication is the primary treatment for motor symptoms in the early stages of Parkinson's disease, while deep brain stimulation has been clinically proven to be effective in alleviating symptoms in patients with advanced Parkinson's disease,particularly for the movement disorders caused by levodopa. Deep brain stimulation targeting the globus pallidus internus can improve motor function in patients with tremordominant and non-tremor-dominant Parkinson's disease, while deep brain stimulation targeting the globus pallidus externus can alter the temporal pattern of neural activity throughout the basal ganglia–thalamus network. Therefore, the composition of the globus pallidus neurons, the neurotransmitters that act on them, their electrical activity,and the neural circuits they form can guide the search for new multi-target drugs to treat Parkinson's disease in clinical practice. Examining the potential intra-nuclear and neural circuit mechanisms of deep brain stimulation associated with the globus pallidus can facilitate the management of both motor and non-motor symptoms while minimizing the side effects caused by deep brain stimulation.

Underlying mechanisms of mindfulness meditation:Genomics,circuits,and networks

Understanding neuropsychological mechanisms of mindfulness meditation(MM)has been a hot topic in recent years.This review was conducted with the goal of synthesizing empirical relationships via the genomics,circuits and networks between MM and mental disorders.We describe progress made in assessing the effects of MM on gene expression in immune cells,with particular focus on stressrelated inflammatory markers and associated biological pathways.We then focus on key brain circuits associated with mindfulness practices and effects on symptoms of mental disorders,and expand our discussion to identify three key brain networks associated with mindfulness practices including default mode network,central executive network,and salience network.More research efforts need to be devoted into identifying underlying neuropsychological mechanisms of MM on how it alleviates the symptoms of mental disorders.

Optimising repetitive transcranial magnetic stimulation for neural circuit repair following traumatic brain injury

While it is well-known that neuronal activity promotes plasticity and connectivity, the success of activity-based neural rehabilitation programs remains extremely limited in human clinical experience because they cannot adequately control neuronal excitability and activity within the injured brain in order to induce repair. However, it is possible to non-invasively modulate brain plasticity using brain stimu- lation techniques such as repetitive transcranial （rTMS） and transcranial direct current stimulation （tDCS） techniques, which show promise for repairing injured neural circuits （Henrich-Noack et al., 2013; Lefaucher et al., 2014）. Yet we are far from having full control of these techniques to repair the brain following neurotrauma and need more fundamen- tal research （Ellaway et al., 2014; Lefaucher et al., 2014）. In this perspective we discuss the mechanisms by which rTMS may facilitate neurorehabilitation and propose experimental techniques with which magnetic stimulation may be investi- gated in order to optimise its treatment potential.

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.

Acupuncture for obesity and related diseases:Insight for regulating neural circuit

Obesity is defined as abnormal or excessive fat accumulation that may impair health.Obesity is associated with numerous pathological changes including insulin resistance,fatty liver,hyperlipidemias,and other obesity-related diseases.These comorbidities comprise a significant public health threat.Existing anti-obesity drugs have been limited by side effects that include depression,suicidal thoughts,cardiovascular complications and stroke.Acupuncture treatment has been shown to be effective for treating obesity and obesity-related conditions,while avoiding side effects.However,the mechanisms of acupuncture in treating obesity-related diseases,especially its effect on neural circuits,are not well understood.A growing body of research has studied acupuncture’s effects on the endocrine system and other mechanisms related to the regulation of neural circuits.In this article,recent research that was relevant to the use of acupuncture to treat obesity and obesity-related diseases through the neuroendocrine system,as well as some neural circuits involved,was summarized.Based on this,acupuncture’s potential ability to regulate neural circuits and its mechanisms of action in the endocrine system were reviewed,leading to a deeper mechanistic understanding of acupuncture’s effects and providing insight and direction for future research about obesity.

A Comprehensive Overview of the Neural Mechanisms of Light Therapy

Light is a powerful environmental factor influencing diverse brain functions.Clinical evidence supports the beneficial effect of light therapy on several diseases,including depression,cognitive dysfunction,chronic pain,and sleep disorders.However,the precise mechanisms underlying the effects of light therapy are still not well understood.In this review,we critically evaluate current clinical evidence showing the beneficial effects of light therapy on diseases.In addition,we introduce the research progress regarding the neural circuit mechanisms underlying the modulatory effects of light on brain functions,including mood,memory,pain perception,sleep,circadian rhythm,brain development,and metabolism.

A gas sensing neural circuit for an olfactory neuron

A gas sensor can convert external gas concentration or species into electric voltage or current signals by physical adsorption or chemical changes. As a result, a gas sensor in a nonlinear circuit can be used as a sensitive sensor for detecting external gas signals from the olfactory system. In this paper, a gas sensor and a field-effect transistor are incorporated into a simple FithzHugh–Nagumo neural circuit for capturing and encoding external gas signals. An improved functional neural circuit is obtained, and the effect of gas concentration, gas species and neuronal activity can be discerned as the gate voltage, threshold voltage and activation coefficient of the field-effect transistor, respectively. The gas concentration can affect the neural activities from quiescent to normal working and, finally, to saturation state in bursting, spiking, periodic and chaotic firings with different frequencies. The effects of gas species and neuronal activity on the firing state can also be achieved in this functional neural circuit. In addition, variations in the gate voltage, threshold voltage and activation coefficient can cause switching between different firing modes. These results can be helpful in designing artificial olfactory devices for bionic gas recognition and other coupled systems arising in applied sciences.

A Brief Summary of Current Therapeutic Strategies for Spinal Cord Injury

Spinal cord injury(SCI)is a tremendous disaster in a person’s life.It interrupts the brain-body neuronal circuits,resulting in functional deficits.Pathogenesis of SCI is a progressive and comprehensive event.In clinical trials,attempts to promote nerve regeneration and functional recovery after SCI have met with failures.Recently,with the development of transcriptome sequencing and biomaterials,researchers have struggled to explore novel efficient therapeutic treatments for SCI.Here,we summarize the recent pro-gress that has been made in SCI repair based on the lesion microenvironment,neural circuits,and bioma-terial scaffolds.We also propose several important directions for future research,including targeted-microRNA therapy,blood vessel interventions,and multiple treatment combinations.In short,we hope this review will enlighten researchers in the field and pave the way for SCI therapy.

Neuroimmune crosstalk through brain-derived neurotrophic factor and its precursor pro-BDNF: New insights into mood disorders

Mood disorders are the most common mental disorders, affecting approximately350 million people globally. Recent studies have shown that neuroimmuneinteraction regulates mood disorders. Brain-derived neurotrophic factor (BDNF)and its precursor pro-BDNF, are involved in the neuroimmune crosstalk duringthe development of mood disorders. BDNF is implicated in the pathophysiologyof psychiatric and neurological disorders especially in antidepressant pharmacotherapy.In this review, we describe the functions of BDNF/pro-BDNF signalingin the central nervous system in the context of mood disorders. In addition, wesummarize the developments for BDNF and pro-BDNF functions in mooddisorders. This review aims to provide new insights into the impact ofneuroimmune interaction on mood disorders and reveal a new basis for furtherdevelopment of diagnostic targets and mood disorders.

颞叶癫痫异常神经环路分析(英文)

OBJECTIVE Temporal lobe epilepsy(TLE) is one of the most common types of human epilepsy,and they are often resistant to current treatments. METHODS By using optogenetic,electrophysiological,imaging and pharmacology strategies,we aimed toinvestigate the underlying circuit mechanism of TLE and tried to developthe novel and efficient approach to control epilepsy. RESULTS(1) Deep brain stimulation,especially low frequency stimulation,targeted the epileptic focus and the areas outside of the focus(critical regions for seizure spread),such as entorhinal cortex or subiculum,reduced seizure severity in TLE. Its anti-epileptic effect is time-window dependent and polarity dependent,which shows a promising strategy for treating epileptic seizures.(2) Using an optogenetic strategy,we demonstrated that excitatory projection from entorhinal cortex to hippocampus instructs the brain-stimulation treatments of epilepsy.(3) Our data from both the clinical and experimental studies further demonstrated that a disinhibitory GABAergic neuron-mediated microcircuit in the subiculum contributes to secondary generalized seizures in TLE.(4) Finally,based on abnormal synchronization of the electrical activity in epileptic circuit,we developed electro-responsive hydrogel nanoparticles modified with angiopep-2to facilitate the delivery of the antiepileptic drug phenytoin sodium,which greatly improves the therapeutic index. CONCLUSION Our findings may update the current view of epileptic neuronal networks and suggest possible promising ways for epilepsy treatment.

Modulation of abnormal neuronal circuit in temporal lobe epilepsy

OBJECTIVE Temporal lobe epilepsy(TLE)is one of the most common types of human epilepsy,and they are often resistant to current treatments.METHODS By using optogenetic,electrophysiological,imaging and pharmacology strategies,we aimed toinvestigate the underlying circuit mechanism of TLE and tried to developthe novel and efficient approach to control epilepsy.RESULTS(1)Using micro PET and multichannel EEG recording,we found an abnormal neural network,characterized by early hypometabolism and after discharge spread,during the epileptogenensis of TLE.(2)Deep brain stimulation,especially low frequency stimulation,targeted the epileptic focus and the areas outside of the focus(critical regions for seizure spread),such as the piriform cortex,cerebellum,entorhinal cortex or subiculum,reduced seizure severity in TLE.Its anti-epileptic effect is time-window dependent and polarity dependent,which shows a promising strategy for treating epileptic seizures.(3)Using an optogenetic strategy,we demonstrated that excitatory projection from entorhinal cortex to hippocampus instructs the brain-stimulation treatments of epilepsy.(4)Our data from both the clinical and experimental studies further demonstrated that a disinhibitory GABAergic neuronmediated microcircuit in the subiculum contributes to secondary generalized seizures in TLE.(5)Finally,based on abnormal synchronization of the electrical activity in epileptic circuit,we developed electroresponsive hydrogel nanoparticles modified with angiopep-2 to facilitate the delivery of the antiepileptic drug phenytoin sodium,which greatly improves the therapeutic index.CONCLUSION Our findings may update the current view of epileptic neuronal networks and suggest possible promising ways for epilepsy treatment.