Repetitive traumatic brain injury–induced complement C1–related inflammation impairs long-term hippocampal neurogenesis

Repetitive traumatic brain injury impacts adult neurogenesis in the hippocampal dentate gyrus,leading to long-term cognitive impairment.However,the mechanism underlying this neurogenesis impairment remains unknown.In this study,we established a male mouse model of repetitive traumatic brain injury and performed long-term evaluation of neurogenesis of the hippocampal dentate gyrus after repetitive traumatic brain injury.Our results showed that repetitive traumatic brain injury inhibited neural stem cell proliferation and development,delayed neuronal maturation,and reduced the complexity of neuronal dendrites and spines.Mice with repetitive traumatic brain injuryalso showed deficits in spatial memory retrieval.Moreover,following repetitive traumatic brain injury,neuroinflammation was enhanced in the neurogenesis microenvironment where C1q levels were increased,C1q binding protein levels were decreased,and canonical Wnt/β-catenin signaling was downregulated.An inhibitor of C1 reversed the long-term impairment of neurogenesis induced by repetitive traumatic brain injury and improved neurological function.These findings suggest that repetitive traumatic brain injury–induced C1-related inflammation impairs long-term neurogenesis in the dentate gyrus and contributes to spatial memory retrieval dysfunction.

Co-localization of two-color rAAV2-retro confirms the dispersion characteristics of efferent projections of mitral cells in mouse accessory olfactory bulb

The accessory olfactory bulb(AOB), located at the posterior dorsal aspect of the main olfactory bulb(MOB), is the first brain relay of the accessory olfactory system(AOS), which can parallelly detect and process volatile and nonvolatile social chemosignals and mediate different sexual and social behaviors with the main olfactory system(MOS). However, due to its anatomical location and absence of specific markers, there is a lack of research on the internal and external neural circuits of the AOB. This issue was addressed by singlecolor labeling and fluorescent double labeling using retrograde rAAVs injected into the bed nucleus of the stria terminalis(BST), anterior cortical amygdalar area(ACo), medial amygdaloid nucleus(MeA), and posteromedial cortical amygdaloid area(PMCo) in mice. We demonstrated the effectiveness of this AOB projection neuron labeling method and showed that the mitral cells of the AOB exhibited efferent projection dispersion characteristics similar to those of the MOB. Moreover, there were significant differences in the number of neurons projected to different brain regions, which indicated that each mitral cell in the AOB could project to a different number of neurons in different cortices. These results provide a circuitry basis to help understand the mechanism by which pheromone information is encoded and decoded in the AOS.

Brain Systems Underlying Fundamental Motivations of Human Social Conformity

From birth to adulthood,we often align our behaviors,attitudes,and opinions with a majority,a phenomenon known as social conformity.A seminal framework has proposed that conformity behaviors are mainly driven by three fundamental motives:a desire to gain more information to be accurate,to obtain social approval from others,and to maintain a favorable self-concept.Despite extensive interest in neuroimaging investigation of social conformity,the relationship between brain systems and these fundamental motivations has yet to be established.Here,we reviewed brain imaging findings of social conformity with a componential framework,aiming to reveal the neuropsychological substrates underlying different conformity motivations.First,information-seeking engages the evaluation of social information,information integration,and modification of task-related activity,corresponding to brain networks implicated in reward,cognitive control,and tasks at hand.Second,social acceptance involves the anticipation of social acceptance or rejection and mental state attribution,mediated by networks of reward,punishment,and mentalizing.Third,self-enhancement entails the excessive representation of positive self-related information and suppression of negative self-related information,ingroup favoritism and/or outgroup derogation,and elaborated mentalizing processes to the ingroup,supported by brain systems of reward,punishment,and mentalizing.Therefore,recent brain imaging studies have provided important insights into the fundamental motivations of social conformity in terms of component processes and brain mechanisms.

Cortical Organization of Centrifugal Afferents to the Olfactory Bulb: Mono-and Trans-synaptic Tracing with Recombinant Neurotropic Viral Tracers

Sensory processing is strongly modulated by different brain and behavioral states,and this is based on the top-down modulation.In the olfactory system,local neural circuits in the olfactory bulb(OB)are innervated by centrifugal afferents in order to regulate the processing of olfactory information in the OB under different behavioral states.The purpose of the present study was to explore the organization of neural networks in olfactory-related cortices and modulatory nuclei that give rise to direct and indirect innervations to the glomerular layer(GL)of the OB at the whole-brain scale.Injection of different recombinant attenuated neurotropic viruses into the GL showed that it received direct inputs from each layer in the OB,centrifugal inputs from the ipsilateralanterior olfactory nucleus(AON),anterior piriform cortex(Pir),and horizontal limb of diagonal band of Broca(HDB),and various indirect inputs from bilateral cortical neurons in the AON,Pir,amygdala,entorhinal cortex,hippocampus,HDB,dorsal raphe,median raphe and locus coeruleus.These results provide a circuitry basis that will help further understand the mechanism by which olfactory informationprocessing in the OB is regulated.

Activation of Parvalbumin-Positive Neurons in Both Retina and Primary Visual Cortex Improves the Feature-Selectivity of Primary Visual Cortex Neurons

Several recent studies using either viral or transgenic mouse models have shown different results on whether the activation of parvalbumin-positive（PV~＋）neurons expressing channelrhodopsin-2（ChR2） in the primary visual cortex（V1） improves the orientation-and direction-selectivity of V1 neurons. Although this discrepancy was thoroughly discussed in a follow-up communication, the issue of using different models to express ChR2 in V1 was not mentioned. We found that ChR2 was expressed in retinal ganglion cells（RGCs） and V1 neurons in ChR2fl/~＋; PV-Cre mice. Our results showed that the activation of PV~＋RGCs using white drifting gratings alone significantly decreased the firing rates of V1 neurons and improved their direction-and orientation-selectivity. Longduration activation of PV~＋interneurons in V1 further enhanced the feature-selectivity of V1 neurons in anesthetized mice, confirming the conclusions from previous findings. These results suggest that the activation of both PV~＋RGCs and V1 neurons improves feature-selectivity in mice.

Short-Term Visual Experience Leads to Potentiation of Spontaneous Activity in Mouse Superior Colliculus

Spontaneous activity in the brain maintains an internal structured pattern that reflects the external environment,which is essential for processing information and developing perception and cognition.An essential prerequisite of spontaneous activity for perception is the ability to reverberate external information,such as by potentiation.Yet its role in the processing of potentiation in mouse superior colliculus(SC)neurons is less studied.Here,we used electrophysiological recording,optogenetics,and drug infusion methods to investigate the mechanism of potentiation in SC neurons.We found that visual experience potentiated SC neurons several minutes later in different developmental stages,and the similarity between spontaneous and visually-evoked activity increased with age.Before eye-opening,activation of retinal ganglion cells that expressed ChR2 also induced the potentiation of spontaneous activity in the mouse SC.Potentiation was dependenton stimulus number and showed feature selectivity for direction and orientation.Optogenetic activation of parvalbumin neurons in the SC attenuated the potentiation induced by visual experience.Furthermore,potentiation in SC neurons was blocked by inhibiting the glutamate transporter GLT1.These results indicated that the potentiation induced by a visual stimulus might play a key role in shaping the internal representation of the environment,and serves as a carrier for short-term memory consolidation.

Accurate modulation of photoprinting under stiffness imaging feedback for engineering ECMs with high-fidelity mechanical properties

Engineered extracellular matrices(ECMs)that replicate complex in-vivo features have shown great potential in tissue engineering.Biocompatible hydrogel microstructures have been widely used to replace these native ECMs for physiologically relevant research.However,accurate reproduction of the 3D hierarchical and nonuniform mechanical stffness inside one integrated microstructure to mimic the complex mechanical properties of native ECMs presents a major challenge.Here,by using digital holographic microscopy(DHM)-based stffness imaging feedback,we propose a novel closed-loop control algorithm to achieve high-accuracy control of mechanical properties for hydrogel microstructures that recapitulate the physiological properties of native ECMs with high fidelity.During photoprinting,the photocuring area of the hydrogel is divided into microscale grid areas to locally control the photocuring process.With the assistance of a motorized microfluidic channel,the curing thickness is controlled with layer-by-layer stacking.The DHM-based stiffness imaging feedback allows accurate adjustment of the photocuring degree in every grid area to change the crosslinking network density of the hydrogel,thus enabling large-span and high-resolution modulation of mechanical properties.Finally,the gelatin methacrylate was used as a typical biomaterial to construct the highfidelity biomimetic ECMs.The Young's modulus could be flexibly modulated in the 10 kPa to 50 kPa range.Additionally,the modulus gradient was accurately controlled to within 2.9 kPa.By engineering ECM with locally different mechanical properties,cell spreading along the stff areas was observed successfully.We believe that this method can regenerate complex biomimetic ECMs that closely recapitulate in-vivo mechanical properties for further applications in tissue engineering and biomedical research.

Reduced Firing of Nucleus Accumbens Parvalbumin Interneurons Impairs Risk Avoidance in DISC1 Transgenic Mice

A strong animal survival instinct is to approach objects and situations that are of benefit and to avoid risk.In humans,a large proportion of mental disorders are accompanied by impairments in risk avoidance.One of the most important genes involved in mental disorders is disrupted-in-schizophrenia-1(DISC1),and animal models in which this gene has some level of dysfunction show emotion-related impairments.However,it is not known whether DISC1 mouse models have an impairment in avoiding potential risks.In the present study,we used DISC1-N terminal truncation(DISC1-N^(TM))mice to investigate risk avoidance and found that these mice were impaired in risk avoidance on the elevated plus maze(EPM)and showed reduced social preference in a three-chamber social interaction test.Following EPM tests,c-Fos expression levels indicated that the nucleus accumbens(NAc)was associated with risk-avoidance behavior in DISC1-N^(TM)mice.In addition,in vivo electrophysiological recordings following tamoxifen administration showed that the firing rates of fast-spiking neurons(FS)in the NAc were significantly lower in DISC1-N^(TM)mice than in wild-type(WT)mice.In addition,in vitro patch clamp recording revealed that the frequency of action potentials stimulated by current injection was lower in parvalbumin(PV)neurons in the NAc of DISC1-N^(TM)mice than in WT controls.The impairment of risk avoidance in DISC1-N^(TM)mice was rescued using optogenetic tools that activated NAcPV neurons.Finally,inhibition of the activity of NAcPV neurons in PV-Cre mice mimicked the risk-avoidance impairment found in DISC1-N^(TM)mice during tests on the elevated zero maze.Taken together,our findings confirm an impairment in risk avoidance in DISC1-N^(TM)mice and suggest that reduced excitability of NAc^(PV) neurons is responsible.

Neuronal Network Dissection with Neurotropic Virus Tracing

The brain is a marvel of biological evolution,a highly complex organ including hundreds of different types of about 100 billion neurons.Understanding the structure and function of the brain is one of the most challenging scientific questions in the 21st century.Crucially,the structure of neural circuits and the mechanisms of neuronal information processing related to brain function are still poorly understood[1].A neural circuit is composed of a large number of synaptically connected neurons of different types and characteristics.It is the structural basis for the execution of various functions,such as perception,emotion,memory,and imagination,as well as other activities.Revealing the structure of neural circuits is the basic premise for understanding the mechanism of information processing in the brain[2].

手外科进入“手-脑新纪元”:改变手,重塑脑

Amputated hand,and paralyzed hand,are diseases not on the conventional list of the hand surgery world,but now have gradually become the new direction for hand surgeons.A good example is the advancements in treating amputations after traumatic injury of the upper limb.Targeted muscle reinnervation combined with a highly functional bionic arm can greatly compensate for the missing part of the amputated arm[1],which in general satisfies the need for strength and dexterity in daily life.According to the classic cortical homunculus first drawn by Penfield,the hand area occupied nearly-one-third of the sensorimotor cortex[2].Thus,interventions with the hands enable the modulation of brain function,providing a solution for brain disorders through skillful utilization of brain plasticity.With the recent advancements in neuroscience and biomedical engineering technology,hand surgeons find themselves entering an era with a bigger performance stage than ever before.For paralyzed hand,the most common cause is central neurological diseases such as stroke or cerebral palsy,or paraplegia.Although it is more challenging since surgeons should balance spasticity and motor function at the same time,efforts have been made by hand surgeons around the world,such as hyper selective neurectomy,tendon lengthening or transfer to reduce the spasticity and reconstruct the motor function[3].Considering the fact that the number of patients with paralyzed hands is over 10 million,which far exceeds the traditional nerve injury entity,this area is the potential further direction of hand surgery.In this article,we will discuss the opportunities and pitfalls in the combination of hand surgery techniques and brain-computer-interface(BCI)in treating paralyzed hands from the perspective of hand surgery development.