查看更多>>摘要：Integrating multisensory inputs to generate accurate perception and guide behavior is among the most critical functions of the brain.Subcortical regions such as the amygdala are involved in sensory processing including vision and audition,yet their roles in multisensory integra-tion remain unclear.In this study,we systematically investi-gated the function of neurons in the amygdala and adjacent regions in integrating audiovisual sensory inputs using a semi-chronic multi-electrode array and multiple combina-tions of audiovisual stimuli.From a sample of 332 neurons,we showed the diverse response patterns to audiovisual stimuli and the neural characteristics of bimodal over uni-modal modulation,which could be classified into four types with differentiated regional origins.Using the hierarchical clustering method,neurons were further clustered into five groups and associated with different integrating functions and sub-regions.Finally,regions distinguishing congruent and incongruent bimodal sensory inputs were identified.Overall,visual processing dominates audiovisual integration in the amygdala and adjacent regions.Our findings shed new light on the neural mechanisms of multisensory integration in the primate brain.
查看更多>>摘要：The cochlear auditory epithelium contains two types of sound receptors,inner hair cells(IHCs)and outer hair cells(OHCs).Mouse models for labelling juvenile and adult IHCs or OHCs exist;however,labelling for embryonic and perinatal IHCs or OHCs are lacking.Here,we gener-ated a new knock-in Fgf8P2A-3×GFP/+(Fgf8GFP/+)strain,in which the expression of a series of three GFP fragments is controlled by endogenous Fgf8 cis-regulatory elements.After confirming that GFP expression accurately reflects the expression of Fgf8,we successfully obtained both embry-onic and neonatal IHCs with high purity,highlighting the power of Fgf8GFP/+.Furthermore,our fate-mapping analy-sis revealed,unexpectedly,that IHCs are also derived from inner ear progenitors expressing Insm1,which is currently regarded as an OHC marker.Thus,besides serving as a highly favorable tool for sorting early IHCs,Fgf8GFP/+ will facilitate the isolation of pure early OHCs by excluding IHCs from the entire hair cell pool.
查看更多>>摘要：Deficiencies in the clearance of peripheral amy-loid β(Aβ)play a crucial role in the progression of Alzhei-mer's disease(AD).Previous studies have shown that the ability of blood monocytes to phagocytose Aβ is decreased in AD.However,the exact mechanism of Aβ clearance dys-function in AD monocytes remains unclear.In the present study,we found that blood monocytes in AD mice exhibited decreases in energy metabolism,which was accompanied by cellular senescence,a senescence-associated secretory phenotype,and dysfunctional phagocytosis of Aβ.Improv-ing energy metabolism rejuvenated monocytes and enhanced their ability to phagocytose Aβ in vivo and in vitro.Moreo-ver,enhancing blood monocyte Aβ phagocytosis by improv-ing energy metabolism alleviated brain Aβ deposition and neuroinflammation and eventually improved cognitive func-tion in AD mice.This study reveals a new mechanism of impaired Aβ phagocytosis in monocytes and provides evi-dence that restoring their energy metabolism may be a novel therapeutic strategy for AD.
查看更多>>摘要：Brachial plexus avulsion(BPA)is a combined injury involving the central and peripheral nervous systems.Patients with BPA often experience severe neuropathic pain(NP)in the affected limb.NP is insensitive to the existing treatments,which makes it a challenge to researchers and clinicians.Accumulated evidence shows that a BPA-induced pain state is often accompanied by sympathetic nervous dys-function,which suggests that the excitation state of the sym-pathetic nervous system is correlated with the existence of NP.However,the mechanism of how somatosensory neural crosstalk with the sympathetic nerve at the peripheral level remains unclear.In this study,through using a novel BPA C7 root avulsion mouse model,we found that the expression of BDNF and its receptor TrκB in the DRGs of the BPA mice increased,and the markers of sympathetic nervous system activity including α1 and α2 adrenergic receptors(α1-AR and α2-AR)also increased after BPA.The phe-nomenon of superexcitation of the sympathetic nervous system,including hypothermia and edema of the affected extremity,was also observed in BPA mice by using Cat-Walk gait analysis,an infrared thermometer,and an edema evaluation.Genetic knockdown of BDNF in DRGs not only reversed the mechanical allodynia but also alleviated the hypothermia and edema of the affected extremity in BPA mice.Further,intraperitoneal injection of adrenergic recep-tor inhibitors decreased neuronal excitability in patch clamp recording and reversed the mechanical allodynia of BPA mice.In another branch experiment,we also found the ele-vated expression of BDNF,TrκB,TH,α1-AR,and α2-AR in DRG tissues from BPA patients compared with normal human DRGs through western blot and immunohistochem-istry.Our results revealed that peripheral BDNF is a key molecule in the regulation of somatosensory-sympathetic coupling in BPA-induced NP.This study also opens a novel analgesic target(BDNF)in the treatment of this pain with fewer complications,which has great potential for clinical transformation.
查看更多>>摘要：Itch is an unpleasant sensation that urges people and animals to scratch.Neuroimaging studies on itch have yielded extensive correlations with diverse cortical and sub-cortical regions,including the insular lobe.However,the role and functional specificity of the insular cortex(IC)and its subdivisions in itch mediation remains unclear.Here,we demonstrated by immunohistochemistry and fiber photom-etry tests,that neurons in both the anterior insular cortex(AIC)and the posterior insular cortex(PIC)are activated during acute itch processes.Pharmacogenetic experiments revealed that nonselective inhibition of global AIC neu-rons,or selective inhibition of the activity of glutaminer-gic neurons in the AIC,reduced the scratching behaviors induced by intradermal injection of 5-hydroxytryptamine(5-HT),but not those induced by compound 48/80.How-ever,both nonselective inhibition of global PIC neurons and selective inhibition of glutaminergic neurons in the PIC failed to affect the itching-scratching behaviors induced by either 5-HT or compound 48/80.In addition,pharmacoge-netic inhibition of AIC glutaminergic neurons effectively blocked itch-associated conditioned place aversion behavior,and inhibition of AIC glutaminergic neurons projecting to the prelimbic cortex significantly suppressed 5-HT-evoked scratching.These findings provide preliminary evidence that the AIC is involved,at least partially via aversive emotion mediation,in the regulation of 5-HT-,but not compound 48/80-induced itch.
查看更多>>摘要：Breathing is an intrinsic natural behavior and physiological process that maintains life.The rhythmic exchange of gases regulates the delicate balance of chemi-cal constituents within an organism throughout its lifes-pan.However,chronic airway diseases,including asthma and chronic obstructive pulmonary disease,affect millions of people worldwide.Pathological airway conditions can disrupt respiration,causing asphyxia,cardiac arrest,and potential death.The innervation of the respiratory tract and the action of the immune system confer robust airway sur-veillance and protection against environmental irritants and pathogens.However,aberrant activation of the immune sys-tem or sensitization of the nervous system can contribute to the development of autoimmune airway disorders.Transient receptor potential ion channels and voltage-gated Na+ chan-nels play critical roles in sensing noxious stimuli within the respiratory tract and interacting with the immune system to generate neurogenic inflammation and airway hypersensitiv-ity.Although recent studies have revealed the involvement of nociceptor neurons in airway diseases,the further neural cir-cuitry underlying airway protection remains elusive.Unrave-ling the mechanism underpinning neural circuit regulation in the airway may provide precise therapeutic strategies and valuable insights into the management of airway diseases.
查看更多>>摘要：The mammalian brain is a highly complex net-work that consists of millions to billions of densely-inter-connected neurons.Precise dissection of neural circuits at the mesoscopic level can provide important structural infor-mation for understanding the brain.Optical approaches can achieve submicron lateral resolution and achieve"optical sectioning"by a variety of means,which has the natural advantage of allowing the observation of neural circuits at the mesoscopic level.Automated whole-brain optical imag-ing methods based on tissue clearing or histological sec-tioning surpass the limitation of optical imaging depth in biological tissues and can provide delicate structural infor-mation in a large volume of tissues.Combined with various fluorescent labeling techniques,whole-brain optical imaging methods have shown great potential in the brain-wide quan-titative profiling of cells,circuits,and blood vessels.In this review,we summarize the principles and implementations of various whole-brain optical imaging methods and provide some concepts regarding their future development.
查看更多>>摘要：Audiovisual integration is a vital information process involved in cognition and is closely correlated with aging and Alzheimer's disease(AD).In this review,we eval-uated the altered audiovisual integrative behavioral symp-toms in AD.We further analyzed the relationships between AD pathologies and audiovisual integration alterations bidirectionally and suggested the possible mechanisms of audiovisual integration alterations underlying AD,including the imbalance between energy demand and supply,activity-dependent degeneration,disrupted brain networks,and cog-nitive resource overloading.Then,based on the clinical char-acteristics including electrophysiological and imaging data related to audiovisual integration,we emphasized the value of audiovisual integration alterations as potential biomark-ers for the early diagnosis and progression of AD.We also highlighted that treatments targeted audiovisual integration contributed to widespread pathological improvements in AD animal models and cognitive improvements in AD patients.Moreover,investigation into audiovisual integration altera-tions in AD also provided new insights and comprehension about sensory information processes.
Charlotte SleursPaul FletcherConor MallucciShivaram Avula...
1873-1886页
查看更多>>摘要：The increasing number of long-term survivors of pediatric brain tumors requires us to incorporate the most recent knowledge derived from cognitive neuroscience into their oncological treatment.As the lesion itself,as well as each treatment,can cause specific neural damage,the long-term neurocognitive outcomes are highly complex and chal-lenging to assess.The number of neurocognitive studies in this population grows exponentially worldwide,motivat-ing modern neuroscience to provide guidance in follow-up before,during and after treatment.In this review,we provide an overview of structural and functional brain connectomes and their role in the neuropsychological outcomes of specific brain tumor types.Based on this information,we propose a theoretical neuroscientific framework to apply appropriate neuropsychological and imaging follow-up for future clinical care and rehabilitation trials.
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