查看更多>>摘要：In this study,we explored the neural mechanism underlying impaired stereopsis and possible functional plas-ticity after strabismus surgery.We enrolled 18 stereo-defi-cient patients with intermittent exotropia before and after surgery,along with 18 healthy controls.Functional magnetic resonance imaging data were collected when participants viewed three-dimensional stimuli.Compared with controls,preoperative patients showed hypoactivation in higher-level dorsal(visual and parietal)areas and ventral visual areas.Pre-and postoperative activation did not significantly dif-fer in patients overall;patients with improved stereopsis showed stronger postoperative activation than preoperative activation in the right V3A and left intraparietal sulcus.Worse stereopsis and fusional control were correlated with preoperative hypoactivation,suggesting that cortical deficits along the two streams might reflect impaired stereopsis in intermittent exotropia.The correlation between improved stereopsis and activation in the right V3A after surgery indi-cates that functional plasticity may underlie the improve-ment of stereopsis.Thus,additional postoperative strategies are needed to promote functional plasticity and enhance the recovery of stereopsis.
查看更多>>摘要：The axon initial segment(AIS)is a highly spe-cialized axonal compartment where the action potential is initiated.The heterogeneity of AISs has been suggested to occur between interneurons and pyramidal neurons(PyNs),which likely contributes to their unique spiking properties.However,whether the various characteristics of AISs can be linked to specific PyN subtypes remains unknown.Here,we report that in the prelimbic cortex(PL)of the mouse,two types of PyNs with axon projections either to the contralat-eral PL or to the ipsilateral basal lateral amygdala,possess distinct AIS properties reflected by morphology,ion chan-nel expression,action potential initiation,and axo-axonic synaptic inputs from chandelier cells.Furthermore,projec-tion-specific AIS diversity is more prominent in the superfi-cial layer than in the deep layer.Thus,our study reveals the cortical layer-and axon projection-specific heterogeneity of PyN AISs,which may endow the spiking of various PyN types with exquisite modulation.
查看更多>>摘要：Cortical interneurons can be categorized into distinct populations based on multiple modalities,including molecular signatures and morpho-electrical(M/E)proper-ties.Recently,many transcriptomic signatures based on sin-gle-cell RNA-seq have been identified in cortical interneu-rons.However,whether different interneuron populations defined by transcriptomic signature expressions correspond to distinct M/E subtypes is still unknown.Here,we applied the Patch-PCR approach to simultaneously obtain the M/E properties and messenger RNA(mRNA)expression of＞600 interneurons in layer V of the mouse somatosensory cortex(S1).Subsequently,we identified 11 M/E subtypes,9 neurochemical cell populations(NCs),and 20 transcrip-tomic cell populations(TCs)in this cortical lamina.Further analysis revealed that cells in many NCs and TCs comprised several M/E types and were difficult to clearly distinguish morpho-electrically.A similar analysis of layer V interneu-rons of mouse primary visual cortex(V1)and motor cortex(M1)gave results largely comparable to S1.Comparison between S1,V1,and M1 suggested that,compared to V1,S1 interneurons were morpho-electrically more similar to M1.Our study reveals the presence of substantial M/E varia-tions in cortical interneuron populations defined by molecu-lar expression.
查看更多>>摘要：Gene transcription and new protein synthesis regulated by epigenetics play integral roles in the formation of new memories.However,as an important part of epi-genetics,the function of chromatin remodeling in learning and memory has been less studied.Here,we showed that SMARCA5(SWI/SNF related,matrix-associated,actin-dependent regulator of chromatin,subfamily A,member 5),a critical chromatin remodeler,was responsible for hip-pocampus-dependent memory maintenance and neurogen-esis.Using proteomics analysis,we found protein expres-sion changes in the hippocampal dentate gyrus(DG)after the knockdown of SMARCA5 during contextual fear con-ditioning(CFC)memory maintenance in mice.Moreover,SMARCA5 was revealed to participate in CFC memory maintenance via modulating the proteins of metabolic path-ways such as nucleoside diphosphate kinase-3(NME3)and aminoacylase 1(ACY1).This work is the first to describe the role of SMARCA5 in memory maintenance and to dem-onstrate the involvement of metabolic pathways regulated by SMARCA5 in learning and memory.
Maksim ZhuravlevMikhail NovikovRuzanna ParsamyanAnton Selskii...
1105-1116页
查看更多>>摘要：The article presents an original method for the automatic assessment of the quality of event-related poten-tials(ERPs),based on the calculation of the coefficient ε,which describes the compliance of recorded ERPs with some statistically significant parameters.This method was used to analyze the neuropsychological EEG monitoring of patients suffering from migraines.The frequency of migraine attacks was correlated with the spatial distribution of the coefficientsε,calculated for EEG channels.More than 15 migraine attacks per month was accompanied by an increase in calcu-lated values in the occipital region.Patients with infrequent migraines exhibited maximum quality in the frontal areas.The automatic analysis of spatial maps of the coefficient ε demonstrated a statistically significant difference between the two analyzed groups with different means of migraine attack numbers per month.
查看更多>>摘要：Resveratrol(RES),a natural polyphenolic phyto-chemical,has been suggested as a putative anti-aging mole-cule for the prevention and treatment of Alzheimer's disease(AD)by the activation of sirtuin 1(Sirt1/Sir2).In this study,we tested the effects of RES and Sirt1/Sir2 on sleep and courtship memory in a Drosophila model by overexpression of amyloid precursor protein(APP),whose duplications and mutations cause familial AD.We found a mild but signifi-cant transcriptional increase of Drosophila Sir2(dSir2)by RES supplementation for up to 17 days in APP flies,but not for 7 days.RES and dSir2 almost completely reversed the sleep and memory deficits in APP flies.We further dem-onstrated that dSir2 acts as a sleep promotor in Drosophila neurons.Interestingly,RES increased sleep in the absence of dSir2 in dSir2-null mutants,and RES further enhanced sleep when dSir2 was either overexpressed or knocked down in APP flies.Finally,we showed that Aβ aggregates in APP flies were reduced by RES and dSir2,probably via inhibiting Drosophila β-secretase(dBACE).Our data suggest that RES rescues the APP-induced behavioral deficits and Aβ burden largely,but not exclusively,via dSir2.
查看更多>>摘要：Heterozygous loss-of-function variants of FOXP4 are associated with neurodevelopmental disorders(NDDs)that exhibit delayed speech development,intel-lectual disability,and congenital abnormalities.The etiol-ogy of NDDs is unclear.Here we found that FOXP4 and N-cadherin are expressed in the nuclei and apical end-feet of radial glial cells(RGCs),respectively,in the mouse neo-cortex during early gestation.Knockdown or dominant-neg-ative inhibition of Foxp4 abolishes the apical condensation of N-cadherin in RGCs and the integrity of neuroepithelium in the ventricular zone(VZ).Inhibition of Foxp4 leads to impeded radial migration of cortical neurons and ectopic neurogenesis from the proliferating VZ.The ectopic differ-entiation and deficient migration disappear when N-cadherin is over-expressed in RGCs.The data indicate that Foxp4 is essential for N-cadherin-based adherens junctions,the loss of which leads to periventricular heterotopias.We hypoth-esize that FOXP4 variant-associated NDDs may be caused by disruption of the adherens junctions and malformation of the cerebral cortex.
查看更多>>摘要：Hv1 is the only voltage-gated proton-selective channel in mammalian cells.It contains a conserved volt-age-sensor domain,shared by a large class of voltage-gated ion channels,but lacks a pore domain.Its primary role is to extrude protons from the cytoplasm upon pH reduction and membrane depolarization.The best-known function of Hv1 is the regulation of cytosolic pH and the nicotinamide adenine dinucleotide phosphate oxidase-dependent produc-tion of reactive oxygen species.Accumulating evidence indicates that Hv1 is expressed in nervous systems,in addi-tion to immune cells and others.Here,we summarize the molecular properties,distribution,and physiological func-tions of Hv1 in the peripheral and central nervous systems.We describe the recently discovered functions of Hv1 in various neurological diseases,including brain or spinal cord injury,ischemic stroke,demyelinating diseases,and pain.We also summarize the current advances in the discovery and application of Hv1-targeted small molecules in neuro-logical diseases.Finally,we discuss the current limitations of our understanding of Hv1 and suggest future research directions.
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