Glaucoma is a leading cause of irreve rsible blindness wo rldwide,and previous studies have shown that,in addition to affecting the eyes,it also causes abnormalities in the brain.However,it is not yet clear how the pr...Glaucoma is a leading cause of irreve rsible blindness wo rldwide,and previous studies have shown that,in addition to affecting the eyes,it also causes abnormalities in the brain.However,it is not yet clear how the primary visual cortex(V1)is altered in glaucoma.This study used DBA/2J mice as a model for spontaneous secondary glaucoma.The aim of the study was to compare the electrophysiological and histomorphological chara cteristics of neurons in the V1between 9-month-old DBA/2J mice and age-matched C57BL/6J mice.We conducted single-unit recordings in the V1 of light-anesthetized mice to measure the visually induced responses,including single-unit spiking and gamma band oscillations.The morphology of layerⅡ/Ⅲneurons was determined by neuronal nuclear antigen staining and Nissl staining of brain tissue sections.Eighty-seven neurons from eight DBA/2J mice and eighty-one neurons from eight C57BL/6J mice were examined.Compared with the C57BL/6J group,V1 neurons in the DBA/2J group exhibited weaker visual tuning and impaired spatial summation.Moreove r,fewer neuro ns were observed in the V1 of DBA/2J mice compared with C57BL/6J mice.These findings suggest that DBA/2J mice have fewer neurons in the VI compared with C57BL/6J mice,and that these neurons have impaired visual tuning.Our findings provide a better understanding of the pathological changes that occur in V1 neuron function and morphology in the DBA/2J mouse model.This study might offer some innovative perspectives regarding the treatment of glaucoma.展开更多
Vascular endothelial growth factor(VEGF)was discovered by its angiogenic activity.However,during evolution,it appeared earlier as a neurotrophic factor required for the development of the nervous system in invertebrat...Vascular endothelial growth factor(VEGF)was discovered by its angiogenic activity.However,during evolution,it appeared earlier as a neurotrophic factor required for the development of the nervous system in invertebrates lacking a circulatory system.We aimed at reviewing recent evidence indicating that VEGF has neuroprotective effects in neurons exposed to a variety of insults.Of particular interest is the link established between VEGF and motoneurons,especially after the design of the VEGFδ/δmutant mice.These mice are characterized by low levels of VEGF and develop muscle weakness and motoneuron degeneration resembling amyotrophic lateral sclerosis.The administration of VEGF through several routes to animal models of amyotrophic lateral sclerosis delays motor impairment and motoneuron degeneration and increases life expectancy.There are new recent advances in the role of VEGF in the physiology of motoneurons.Our experimental aims use the extraocular(abducens)motoneurons lesioned by axotomy as a model for studying VEGF actions.Axotomized abducens motoneurons exhibit severe alterations in their discharge activity and a loss of synaptic boutons.The exogenous administration of VEGF to axotomized abducens motoneurons,either from the transected nerve or intraventricularly,fully restores the synaptic and discharge properties of abducens motoneurons,despite being axotomized.In addition,when an anti-VEGF neutralizing antibody is delivered from the muscle to intact,uninjured abducens motoneurons,these cells display alterations in their discharge pattern and a loss of synaptic boutons that resemble the state of axotomy.All these data indicate that VEGF is an essential neurotrophic factor for motoneurons.展开更多
Methcathinone(MCAT)belongs to the designer drugs called synthetic cathinones,which are abused worldwide for recreational purposes.It has strong stimulant effects,including enhanced euphoria,sensation,alertness,and emp...Methcathinone(MCAT)belongs to the designer drugs called synthetic cathinones,which are abused worldwide for recreational purposes.It has strong stimulant effects,including enhanced euphoria,sensation,alertness,and empathy.However,little is known about how MCAT modulates neuronal activity in vivo.Here,we evaluated the effect of MCAT on neuronal activity with a series of functional approaches.C-Fos immunostaining showed that MCAT increased the number of activated neurons by 6-fold,especially in sensory and motor cortices,striatum,and midbrain motor nuclei.In vivo single-unit recording and two-photon Ca^(2+) imaging revealed that a large proportion of neurons increased spiking activity upon MCAT administration.Notably,MCAT induced a strong de-correlation of population activity and increased trial-to-trial reliability,specifically during a natural movie stimulus.It improved the information-processing efficiency by enhancing the single-neuron coding capacity,suggesting a cortical network mechanism of the enhanced perception produced by psychoactive stimulants.展开更多
基金supported by the STI 2030-Major Projects 2022ZD0208500(to DY)the National Natural Science Foundation of China,Nos.82072011(to YX),82121003(to DY),82271120(to YS)+2 种基金Sichuan Science and Technology Program,No.2022ZYD0066(to YS)a grant from Chinese Academy of Medical Science,No.2019-12M-5-032(to YS)the Fundamental Research Funds for the Central Universities,No.ZYGX2021YGLH219(to KC)。
文摘Glaucoma is a leading cause of irreve rsible blindness wo rldwide,and previous studies have shown that,in addition to affecting the eyes,it also causes abnormalities in the brain.However,it is not yet clear how the primary visual cortex(V1)is altered in glaucoma.This study used DBA/2J mice as a model for spontaneous secondary glaucoma.The aim of the study was to compare the electrophysiological and histomorphological chara cteristics of neurons in the V1between 9-month-old DBA/2J mice and age-matched C57BL/6J mice.We conducted single-unit recordings in the V1 of light-anesthetized mice to measure the visually induced responses,including single-unit spiking and gamma band oscillations.The morphology of layerⅡ/Ⅲneurons was determined by neuronal nuclear antigen staining and Nissl staining of brain tissue sections.Eighty-seven neurons from eight DBA/2J mice and eighty-one neurons from eight C57BL/6J mice were examined.Compared with the C57BL/6J group,V1 neurons in the DBA/2J group exhibited weaker visual tuning and impaired spatial summation.Moreove r,fewer neuro ns were observed in the V1 of DBA/2J mice compared with C57BL/6J mice.These findings suggest that DBA/2J mice have fewer neurons in the VI compared with C57BL/6J mice,and that these neurons have impaired visual tuning.Our findings provide a better understanding of the pathological changes that occur in V1 neuron function and morphology in the DBA/2J mouse model.This study might offer some innovative perspectives regarding the treatment of glaucoma.
基金supported by the I+D+i project P20_00529 Consejería de Transformación Económica Industria y Conocimiento,Junta de Andalucía-FEDERsupported by project PGC2018-094654-B-100 and PID2021-124300NB-I00 funded by MCIN/AEI/FEDER“A way of making Europe”+1 种基金P.M.C.was a scholar of Ministerio de Educación y Ciencia(BES-2016-077912)in Spain and is now a“Margarita Salas”postdoctoral fellowRGH is a postdoctoral fellow from PAIDI-2019,“Talento Doctores”Junta de Andalucía in Spain,and is now a“Ramón y Cajal”fellow in Spain。
文摘Vascular endothelial growth factor(VEGF)was discovered by its angiogenic activity.However,during evolution,it appeared earlier as a neurotrophic factor required for the development of the nervous system in invertebrates lacking a circulatory system.We aimed at reviewing recent evidence indicating that VEGF has neuroprotective effects in neurons exposed to a variety of insults.Of particular interest is the link established between VEGF and motoneurons,especially after the design of the VEGFδ/δmutant mice.These mice are characterized by low levels of VEGF and develop muscle weakness and motoneuron degeneration resembling amyotrophic lateral sclerosis.The administration of VEGF through several routes to animal models of amyotrophic lateral sclerosis delays motor impairment and motoneuron degeneration and increases life expectancy.There are new recent advances in the role of VEGF in the physiology of motoneurons.Our experimental aims use the extraocular(abducens)motoneurons lesioned by axotomy as a model for studying VEGF actions.Axotomized abducens motoneurons exhibit severe alterations in their discharge activity and a loss of synaptic boutons.The exogenous administration of VEGF to axotomized abducens motoneurons,either from the transected nerve or intraventricularly,fully restores the synaptic and discharge properties of abducens motoneurons,despite being axotomized.In addition,when an anti-VEGF neutralizing antibody is delivered from the muscle to intact,uninjured abducens motoneurons,these cells display alterations in their discharge pattern and a loss of synaptic boutons that resemble the state of axotomy.All these data indicate that VEGF is an essential neurotrophic factor for motoneurons.
基金supported by the National Natural Science Foundation of China(31871089 and 31871028)Junior Thousand Talents Program of China,Fundamental Research Funds for the Central Universities(HUST:2172019kfyXKJC077 and HUST:2172019kfyRCPY064)Key Laboratory of Forensic Toxicology,Ministry of Public Security of China(Beijing Municipal Public Security Bureau:2020FTDWFX02 and 2019FTDWFX06).
文摘Methcathinone(MCAT)belongs to the designer drugs called synthetic cathinones,which are abused worldwide for recreational purposes.It has strong stimulant effects,including enhanced euphoria,sensation,alertness,and empathy.However,little is known about how MCAT modulates neuronal activity in vivo.Here,we evaluated the effect of MCAT on neuronal activity with a series of functional approaches.C-Fos immunostaining showed that MCAT increased the number of activated neurons by 6-fold,especially in sensory and motor cortices,striatum,and midbrain motor nuclei.In vivo single-unit recording and two-photon Ca^(2+) imaging revealed that a large proportion of neurons increased spiking activity upon MCAT administration.Notably,MCAT induced a strong de-correlation of population activity and increased trial-to-trial reliability,specifically during a natural movie stimulus.It improved the information-processing efficiency by enhancing the single-neuron coding capacity,suggesting a cortical network mechanism of the enhanced perception produced by psychoactive stimulants.