A deficit in spatial memory has been taken as an early predictor of Alzheimer’s disease(AD)or mild cognitive impairment(MCI).The uncinate fasciculus(UF)is a long-range white-matter tract that connects the anterior te...A deficit in spatial memory has been taken as an early predictor of Alzheimer’s disease(AD)or mild cognitive impairment(MCI).The uncinate fasciculus(UF)is a long-range white-matter tract that connects the anterior temporal lobe with the orbitofrontal cortex(OFC)in primates.Previous studies have shown that the UF impairment associated with spatial memory deficits may be an important pathological change in aging and AD,but its exact role in spatial memory is not well understood.The pathway arising from the postrhinal cortex(POR)and projecting to the ventrolateral orbitofrontal cortex(vlOFC)performs most of the functions of the UF in rodents.Although the literature suggests an association between spatial memory and the regions connected by the POR–vlOFC pathway,the function of the pathway in spatialmemory is relatively unknown.To further illuminate the function of the UF in spatial memory,we dissected the POR–vlOFC pathway in mice.We determined that the POR–vlOFC pathway is a glutamatergic structure,and that glutamatergic neurons in the POR regulate spatial memory retrieval.We also demonstrated that the POR–vlOFC pathway specifically transmits spatial information to participate in memory retrieval.These findings provide a deeper understanding of UF function and dysfunction related to disorders of memory,as in MCI and AD.展开更多
The parahippocampal gyrus-orbitofrontal cortex(PHG-OFC)circuit in humans is homologous to the postrhinal cortex(POR)-ventral lateral orbitofrontal cortex(vlOFC)circuit in rodents.Both are associated with visuospatial ...The parahippocampal gyrus-orbitofrontal cortex(PHG-OFC)circuit in humans is homologous to the postrhinal cortex(POR)-ventral lateral orbitofrontal cortex(vlOFC)circuit in rodents.Both are associated with visuospatial malfunctions in Alzheimer’s disease(AD).However,the underlying mechanisms remain to be elucidated.In this study,we explored the relationship between an impaired POR-vlOFC circuit and visuospatial memory deficits through retrograde tracing and in vivo local field potential recordings in 5XFAD mice,and investigated alterations of the PHG-OFC circuit by multi-domain magnetic resonance imaging(MRI)in patients on the AD spectrum.We demonstrated that an impaired glutamatergic POR-vlOFC circuit resulted in deficient visuospatial memory in 5XFAD mice.Moreover,MRI measurements of the PHG-OFC circuit had an accuracy of 77.33%for the classification of amnestic mild cognitive impairment converters versus non-converters.Thus,the PHG-OFC circuit explains the neuroanatomical basis of visuospatial memory deficits in AD,thereby providing a potential predictor for AD progression and a promising interventional approach for AD.展开更多
基金supported by the National Major Science and Technology Program of China(2016YFC1306700)the National Natural Science Foundation of China(81420108012,81671046,81425010 and 31630031)+1 种基金the Jiangsu Provincial Medical Program for Distinguished Scholars(2016006)Postgraduate Research&Practice Innovation Program of Jiangsu Province(KYCX18_0167),China
文摘A deficit in spatial memory has been taken as an early predictor of Alzheimer’s disease(AD)or mild cognitive impairment(MCI).The uncinate fasciculus(UF)is a long-range white-matter tract that connects the anterior temporal lobe with the orbitofrontal cortex(OFC)in primates.Previous studies have shown that the UF impairment associated with spatial memory deficits may be an important pathological change in aging and AD,but its exact role in spatial memory is not well understood.The pathway arising from the postrhinal cortex(POR)and projecting to the ventrolateral orbitofrontal cortex(vlOFC)performs most of the functions of the UF in rodents.Although the literature suggests an association between spatial memory and the regions connected by the POR–vlOFC pathway,the function of the pathway in spatialmemory is relatively unknown.To further illuminate the function of the UF in spatial memory,we dissected the POR–vlOFC pathway in mice.We determined that the POR–vlOFC pathway is a glutamatergic structure,and that glutamatergic neurons in the POR regulate spatial memory retrieval.We also demonstrated that the POR–vlOFC pathway specifically transmits spatial information to participate in memory retrieval.These findings provide a deeper understanding of UF function and dysfunction related to disorders of memory,as in MCI and AD.
基金Supported by the National Natural Science Foundation of China (81420108012,81671046,91832000,and 31700936)the Program of Excellent Talents in Medical Science of Jiangsu Province,China (JCRCA2016006)+4 种基金a Special Project of Clinical Medicine Science and Technology in Jiangsu Province,China (BL2014077)a Guangdong Province Grant (2017A030310496)Key-Area Research and Development Program of Guangdong Province,China (2018B030331001)a National Special Support Grant (W02020453)Guangdong Provincial Key Laboratory of Brain Connectome and Behavior (2017B030301017)。
文摘The parahippocampal gyrus-orbitofrontal cortex(PHG-OFC)circuit in humans is homologous to the postrhinal cortex(POR)-ventral lateral orbitofrontal cortex(vlOFC)circuit in rodents.Both are associated with visuospatial malfunctions in Alzheimer’s disease(AD).However,the underlying mechanisms remain to be elucidated.In this study,we explored the relationship between an impaired POR-vlOFC circuit and visuospatial memory deficits through retrograde tracing and in vivo local field potential recordings in 5XFAD mice,and investigated alterations of the PHG-OFC circuit by multi-domain magnetic resonance imaging(MRI)in patients on the AD spectrum.We demonstrated that an impaired glutamatergic POR-vlOFC circuit resulted in deficient visuospatial memory in 5XFAD mice.Moreover,MRI measurements of the PHG-OFC circuit had an accuracy of 77.33%for the classification of amnestic mild cognitive impairment converters versus non-converters.Thus,the PHG-OFC circuit explains the neuroanatomical basis of visuospatial memory deficits in AD,thereby providing a potential predictor for AD progression and a promising interventional approach for AD.
