The Chinese tree shrew has gained prominence as a model organism due to its phylogenetic proximity to primates,offering distinct advantages over traditional rodent models in biomedical research.However,the neuroanatom...The Chinese tree shrew has gained prominence as a model organism due to its phylogenetic proximity to primates,offering distinct advantages over traditional rodent models in biomedical research.However,the neuroanatomy of this species remains insufficiently defined,limiting its utility in neurophysiological and neuropathological studies.In this study,immunofluorescence microscopy was employed to comprehensively map the distribution of three calciumbinding proteins,parvalbumin,calbindin D-28k,and calretinin,across the tree shrew cerebrum.Serial brain sections in sagittal,coronal,and horizontal planes from 12 individuals generated a dataset of 3638 cellular-resolution images.This dataset,accessible via Science Data Bank(https://doi.org/10.57760/sciencedb.23471),provides detailed region-and laminar-selective distributions of calcium-binding proteins valuable for the cyto-and chemoarchitectural characterization of the tree shrew cerebrum.This resource will not only advance our understanding of brain organization and facilitate basic and translational neuroscience research in tree shrews but also enhance comparative and evolutionary analyses across species.展开更多
AIM:To investigate the postnatal development of parvalbumin(PV)-positive gamma-aminobutyric acid(GABA)interneurons and the co-expression of perineuronal nets(PNNs)and PV in the visual cortex of rats,as well as the reg...AIM:To investigate the postnatal development of parvalbumin(PV)-positive gamma-aminobutyric acid(GABA)interneurons and the co-expression of perineuronal nets(PNNs)and PV in the visual cortex of rats,as well as the regulatory effects of fluoxetine(FLX)treatment and binocular form deprivation(BFD)on these indices.METHODS:Wistar rats were assigned to three experimental cohorts:1)Age-related groups:postnatal week(PW)1,PW3,PW5,PW7,and PW9;2)FLX treatment duration groups:FLX 0W,FLX 2W,FLX 4W,FLX 6W,and FLX 8W;3)Intervention groups:control(Cont),FLX,BFD,and BFD+FLX.The levels of PNNs,PV,and PNNs/PV coexpression in the visual cortex were detected and analyzed.RESULTS:The density of PV-positive cells and the coexpression of PNNs and PV increased gradually with the maturation of the visual cortex(b=0.960,P<0.01).The ratio of PV-positive cells surrounded by PNNs to total PV-positive cells(PNNs+/PV+/total PV+)was significantly decreased in the FLX 4W group(χ^(2)=9.03,P=0.003).There was no significant difference in the PNNs+/PV+/total PV+ratio between the FLX and BFD groups(χ^(2)=1.08,P=0.161),but a significant difference was observed between the BFD+FLX group and the BFD group(χ^(2)=5.82,P<0.01).CONCLUSION:The number of PV-positive neurons and PNNs-surrounded PV neurons in the rat visual cortex increases postnatally and reaches adult levels by postnatal week 7.Chronic FLX treatment downregulates these expressions.Combined 4-week FLX treatment and BFD exerts a more significant inhibitory effect on the PNNs+/PV+/total PV+ratio than either intervention alone.展开更多
Parvalbumin-positive(PV^(+))interneuron dysfunction is believed to be linked to autism spectrum disorder(ASD),a neurodevelopmental disorder characterized by social deficits and stereotypical behaviors.However,the mech...Parvalbumin-positive(PV^(+))interneuron dysfunction is believed to be linked to autism spectrum disorder(ASD),a neurodevelopmental disorder characterized by social deficits and stereotypical behaviors.However,the mechanisms behind PV^(+)interneuron dysfunction remain largely unclear.Here,we found that a deficiency of Biorientation Defective 1(Bod1)in PV^(+)interneurons led to an ASD-like phenotype in Pvalb-Cre;Bod1f/f mice.Mechanistically,we observed that Bod1 deficiency induced hypoactivity of PV^(+)interneurons and hyperactivity of calcium/calmodulin-dependent protein kinaseⅡalpha(CaMKⅡα)neurons in the medial prefrontal cortex,as determined by whole-cell patch-clamp recording.Additionally,Bod1 deficiency decreased the power of highgamma oscillation,assessed by in vivo multi-channel electrophysiological recording.Furthermore,we found that Bod1 deficiency enhanced the inwardly rectifying K^(+)current,leading to an increase in the resting membrane potential of PV^(+)interneurons.Importantly,the gain-of-function of Bod1 improved social deficits and stereotypical behaviors in Pvalb-Cre;Bod1f/f mice.These findings provide mechanistic insights into the PV^(+)interneuron dysfunction and suggest new strategies for developing PV^(+)interneuron-targeted therapies for ASD.展开更多
基金supported by the Science and Technology Innovation(STI)2030-Major Projects(2022ZD0205000 to L.L.)CAS“Light of West China”Program(xbzg-zdsys-202404 to L.L.)+1 种基金Yunnan Revitalization Talent Support Program Yunling Scholar Project(to L.L.)Yunnan Fundamental Research Projects(202305AH340006,202301AS070060 to L.L.,202401AT070206 to X.C.)。
文摘The Chinese tree shrew has gained prominence as a model organism due to its phylogenetic proximity to primates,offering distinct advantages over traditional rodent models in biomedical research.However,the neuroanatomy of this species remains insufficiently defined,limiting its utility in neurophysiological and neuropathological studies.In this study,immunofluorescence microscopy was employed to comprehensively map the distribution of three calciumbinding proteins,parvalbumin,calbindin D-28k,and calretinin,across the tree shrew cerebrum.Serial brain sections in sagittal,coronal,and horizontal planes from 12 individuals generated a dataset of 3638 cellular-resolution images.This dataset,accessible via Science Data Bank(https://doi.org/10.57760/sciencedb.23471),provides detailed region-and laminar-selective distributions of calcium-binding proteins valuable for the cyto-and chemoarchitectural characterization of the tree shrew cerebrum.This resource will not only advance our understanding of brain organization and facilitate basic and translational neuroscience research in tree shrews but also enhance comparative and evolutionary analyses across species.
基金Supported by the Suzhou Science and Technology Bureau(No.SKY2023175)the Project of State Key Laboratory of Radiation Medicine and Protection+6 种基金Soochow University(No.GZK1202309)the Advantage Subject Lifting Project(No.XKTJ-XK202412)the Suzhou Science and Education for Strengthening Healthcare(No.MSXM2024010)the Suzhou Medical Key Supported Disciplines(No.SZFCXK202118)the Youth Scientific Research Fund Project of Kunshan Hospital of Traditional Chinese Medicine(No.2024QNJJ06)the Postgraduate Research&Practice Innovation Program of Jiangsu Province(No.SJCX23_1673)the Undergraduate Training Program for Innovation and Entrepreneurship,Soochow University(No.202310285162Y).
文摘AIM:To investigate the postnatal development of parvalbumin(PV)-positive gamma-aminobutyric acid(GABA)interneurons and the co-expression of perineuronal nets(PNNs)and PV in the visual cortex of rats,as well as the regulatory effects of fluoxetine(FLX)treatment and binocular form deprivation(BFD)on these indices.METHODS:Wistar rats were assigned to three experimental cohorts:1)Age-related groups:postnatal week(PW)1,PW3,PW5,PW7,and PW9;2)FLX treatment duration groups:FLX 0W,FLX 2W,FLX 4W,FLX 6W,and FLX 8W;3)Intervention groups:control(Cont),FLX,BFD,and BFD+FLX.The levels of PNNs,PV,and PNNs/PV coexpression in the visual cortex were detected and analyzed.RESULTS:The density of PV-positive cells and the coexpression of PNNs and PV increased gradually with the maturation of the visual cortex(b=0.960,P<0.01).The ratio of PV-positive cells surrounded by PNNs to total PV-positive cells(PNNs+/PV+/total PV+)was significantly decreased in the FLX 4W group(χ^(2)=9.03,P=0.003).There was no significant difference in the PNNs+/PV+/total PV+ratio between the FLX and BFD groups(χ^(2)=1.08,P=0.161),but a significant difference was observed between the BFD+FLX group and the BFD group(χ^(2)=5.82,P<0.01).CONCLUSION:The number of PV-positive neurons and PNNs-surrounded PV neurons in the rat visual cortex increases postnatally and reaches adult levels by postnatal week 7.Chronic FLX treatment downregulates these expressions.Combined 4-week FLX treatment and BFD exerts a more significant inhibitory effect on the PNNs+/PV+/total PV+ratio than either intervention alone.
基金supported by the National Key Research and Development Program of China(Grant No.2022YFE0108600 to Y.M.L.)the National Natural Science Foundations of China(Grant Nos.82473918 and 82104162 to X.X.L.).
文摘Parvalbumin-positive(PV^(+))interneuron dysfunction is believed to be linked to autism spectrum disorder(ASD),a neurodevelopmental disorder characterized by social deficits and stereotypical behaviors.However,the mechanisms behind PV^(+)interneuron dysfunction remain largely unclear.Here,we found that a deficiency of Biorientation Defective 1(Bod1)in PV^(+)interneurons led to an ASD-like phenotype in Pvalb-Cre;Bod1f/f mice.Mechanistically,we observed that Bod1 deficiency induced hypoactivity of PV^(+)interneurons and hyperactivity of calcium/calmodulin-dependent protein kinaseⅡalpha(CaMKⅡα)neurons in the medial prefrontal cortex,as determined by whole-cell patch-clamp recording.Additionally,Bod1 deficiency decreased the power of highgamma oscillation,assessed by in vivo multi-channel electrophysiological recording.Furthermore,we found that Bod1 deficiency enhanced the inwardly rectifying K^(+)current,leading to an increase in the resting membrane potential of PV^(+)interneurons.Importantly,the gain-of-function of Bod1 improved social deficits and stereotypical behaviors in Pvalb-Cre;Bod1f/f mice.These findings provide mechanistic insights into the PV^(+)interneuron dysfunction and suggest new strategies for developing PV^(+)interneuron-targeted therapies for ASD.
