Degenerate mapping of environmental location presages deficits in object-location encoding and memory in the 5xFAD mouse model for Alzheimer's disease
A key challenge in developing diagnosis and treatments for Alzheimer's disease (AD) is to detect abnormal network activity at as early a stage as possible. To date, behavioral and neurophysiological investigations in AD model mice have yet to conduct a longitudinal assessment of cellular pathol...
| Main Authors: | , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2023-01-01
|
| Series: | Neurobiology of Disease |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S096999612200331X |
| _version_ | 1797978300757311488 |
|---|---|
| author | Hai Zhang Lujia Chen Kevin G. Johnston Joshua Crapser Kim N. Green Nicole My-Linh Ha Andrea J. Tenner Todd C. Holmes Douglas A. Nitz Xiangmin Xu |
| author_facet | Hai Zhang Lujia Chen Kevin G. Johnston Joshua Crapser Kim N. Green Nicole My-Linh Ha Andrea J. Tenner Todd C. Holmes Douglas A. Nitz Xiangmin Xu |
| author_sort | Hai Zhang |
| collection | DOAJ |
| description | A key challenge in developing diagnosis and treatments for Alzheimer's disease (AD) is to detect abnormal network activity at as early a stage as possible. To date, behavioral and neurophysiological investigations in AD model mice have yet to conduct a longitudinal assessment of cellular pathology, memory deficits, and neurophysiological correlates of neuronal activity. We therefore examined the temporal relationships between pathology, neuronal activities and spatial representation of environments, as well as object location memory deficits across multiple stages of development in the 5xFAD mice model and compared these results to those observed in wild-type mice. We performed longitudinal in vivo calcium imaging with miniscope on hippocampal CA1 neurons in behaving mice. We find that 5xFAD mice show amyloid plaque accumulation, depressed neuronal calcium activity during immobile states, and degenerate and unreliable hippocampal neuron spatial tuning to environmental location at early stages by 4 months of age while their object location memory (OLM) is comparable to WT mice. By 8 months of age, 5xFAD mice show deficits of OLM, which are accompanied by progressive degradation of spatial encoding and, eventually, impaired CA1 neural tuning to object-location pairings. Furthermore, depressed neuronal activity and unreliable spatial encoding at early stage are correlated with impaired performance in OLM at 8-month-old. Our results indicate the close connection between impaired hippocampal tuning to object-location and the presence of OLM deficits. The results also highlight that depressed baseline firing rates in hippocampal neurons during immobile states and unreliable spatial representation precede object memory deficits and predict memory deficits at older age, suggesting potential early opportunities for AD detecting. |
| first_indexed | 2024-04-11T05:20:30Z |
| format | Article |
| id | doaj.art-94f303bca8164062b3c45e8aa6ad71c0 |
| institution | Directory Open Access Journal |
| issn | 1095-953X |
| language | English |
| last_indexed | 2024-04-11T05:20:30Z |
| publishDate | 2023-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Neurobiology of Disease |
| spelling | doaj.art-94f303bca8164062b3c45e8aa6ad71c02022-12-24T04:50:15ZengElsevierNeurobiology of Disease1095-953X2023-01-01176105939Degenerate mapping of environmental location presages deficits in object-location encoding and memory in the 5xFAD mouse model for Alzheimer's diseaseHai Zhang0Lujia Chen1Kevin G. Johnston2Joshua Crapser3Kim N. Green4Nicole My-Linh Ha5Andrea J. Tenner6Todd C. Holmes7Douglas A. Nitz8Xiangmin Xu9Department of Anatomy and Neurobiology, School of Medicine, University of California, Irvine, CA 92697, United States of AmericaDepartment of Anatomy and Neurobiology, School of Medicine, University of California, Irvine, CA 92697, United States of America; Department of Biomedical Engineering, University of California, Irvine, CA 92697, United States of AmericaDepartment of Mathematics, University of California, Irvine, CA 92697, United States of AmericaDepartment of Neurobiology and Behavior, School of Biological Sciences, University of California, Irvine, CA 92697, United States of AmericaDepartment of Neurobiology and Behavior, School of Biological Sciences, University of California, Irvine, CA 92697, United States of America; Center for Neural Circuit Mapping, University of California, Irvine, CA 92697, United States of AmericaDepartment of Anatomy and Neurobiology, School of Medicine, University of California, Irvine, CA 92697, United States of AmericaDepartment of Molecular Biology and Biochemistry, School of Biological Sciences, University of California, Irvine, CA 92697, United States of AmericaDepartment of Physiology and Biophysics, School of Medicine, University of California, Irvine, CA 92697, United States of America; Center for Neural Circuit Mapping, University of California, Irvine, CA 92697, United States of AmericaDepartment of Cognitive Science, University of California, San Diego, La Jolla, CA 92093, United States of America; Center for Neural Circuit Mapping, University of California, Irvine, CA 92697, United States of America; Correspondence to: Douglas A. Nitz, Department of Cognitive Science, University of California, San Diego, La Jolla, CA 92093, United States of America.Department of Anatomy and Neurobiology, School of Medicine, University of California, Irvine, CA 92697, United States of America; Department of Biomedical Engineering, University of California, Irvine, CA 92697, United States of America; Center for Neural Circuit Mapping, University of California, Irvine, CA 92697, United States of America; Correspondence to: Xiangmin Xu, Department of Anatomy and Neurobiology, School of Medicine, University of California, Irvine, CA 92697-1275, United States of America.A key challenge in developing diagnosis and treatments for Alzheimer's disease (AD) is to detect abnormal network activity at as early a stage as possible. To date, behavioral and neurophysiological investigations in AD model mice have yet to conduct a longitudinal assessment of cellular pathology, memory deficits, and neurophysiological correlates of neuronal activity. We therefore examined the temporal relationships between pathology, neuronal activities and spatial representation of environments, as well as object location memory deficits across multiple stages of development in the 5xFAD mice model and compared these results to those observed in wild-type mice. We performed longitudinal in vivo calcium imaging with miniscope on hippocampal CA1 neurons in behaving mice. We find that 5xFAD mice show amyloid plaque accumulation, depressed neuronal calcium activity during immobile states, and degenerate and unreliable hippocampal neuron spatial tuning to environmental location at early stages by 4 months of age while their object location memory (OLM) is comparable to WT mice. By 8 months of age, 5xFAD mice show deficits of OLM, which are accompanied by progressive degradation of spatial encoding and, eventually, impaired CA1 neural tuning to object-location pairings. Furthermore, depressed neuronal activity and unreliable spatial encoding at early stage are correlated with impaired performance in OLM at 8-month-old. Our results indicate the close connection between impaired hippocampal tuning to object-location and the presence of OLM deficits. The results also highlight that depressed baseline firing rates in hippocampal neurons during immobile states and unreliable spatial representation precede object memory deficits and predict memory deficits at older age, suggesting potential early opportunities for AD detecting.http://www.sciencedirect.com/science/article/pii/S096999612200331XAnimal modelhippocampusCA1Object location memorySpatial encodingDisease progression |
| spellingShingle | Hai Zhang Lujia Chen Kevin G. Johnston Joshua Crapser Kim N. Green Nicole My-Linh Ha Andrea J. Tenner Todd C. Holmes Douglas A. Nitz Xiangmin Xu Degenerate mapping of environmental location presages deficits in object-location encoding and memory in the 5xFAD mouse model for Alzheimer's disease Neurobiology of Disease Animal model hippocampus CA1 Object location memory Spatial encoding Disease progression |
| title | Degenerate mapping of environmental location presages deficits in object-location encoding and memory in the 5xFAD mouse model for Alzheimer's disease |
| title_full | Degenerate mapping of environmental location presages deficits in object-location encoding and memory in the 5xFAD mouse model for Alzheimer's disease |
| title_fullStr | Degenerate mapping of environmental location presages deficits in object-location encoding and memory in the 5xFAD mouse model for Alzheimer's disease |
| title_full_unstemmed | Degenerate mapping of environmental location presages deficits in object-location encoding and memory in the 5xFAD mouse model for Alzheimer's disease |
| title_short | Degenerate mapping of environmental location presages deficits in object-location encoding and memory in the 5xFAD mouse model for Alzheimer's disease |
| title_sort | degenerate mapping of environmental location presages deficits in object location encoding and memory in the 5xfad mouse model for alzheimer s disease |
| topic | Animal model hippocampus CA1 Object location memory Spatial encoding Disease progression |
| url | http://www.sciencedirect.com/science/article/pii/S096999612200331X |
| work_keys_str_mv | AT haizhang degeneratemappingofenvironmentallocationpresagesdeficitsinobjectlocationencodingandmemoryinthe5xfadmousemodelforalzheimersdisease AT lujiachen degeneratemappingofenvironmentallocationpresagesdeficitsinobjectlocationencodingandmemoryinthe5xfadmousemodelforalzheimersdisease AT kevingjohnston degeneratemappingofenvironmentallocationpresagesdeficitsinobjectlocationencodingandmemoryinthe5xfadmousemodelforalzheimersdisease AT joshuacrapser degeneratemappingofenvironmentallocationpresagesdeficitsinobjectlocationencodingandmemoryinthe5xfadmousemodelforalzheimersdisease AT kimngreen degeneratemappingofenvironmentallocationpresagesdeficitsinobjectlocationencodingandmemoryinthe5xfadmousemodelforalzheimersdisease AT nicolemylinhha degeneratemappingofenvironmentallocationpresagesdeficitsinobjectlocationencodingandmemoryinthe5xfadmousemodelforalzheimersdisease AT andreajtenner degeneratemappingofenvironmentallocationpresagesdeficitsinobjectlocationencodingandmemoryinthe5xfadmousemodelforalzheimersdisease AT toddcholmes degeneratemappingofenvironmentallocationpresagesdeficitsinobjectlocationencodingandmemoryinthe5xfadmousemodelforalzheimersdisease AT douglasanitz degeneratemappingofenvironmentallocationpresagesdeficitsinobjectlocationencodingandmemoryinthe5xfadmousemodelforalzheimersdisease AT xiangminxu degeneratemappingofenvironmentallocationpresagesdeficitsinobjectlocationencodingandmemoryinthe5xfadmousemodelforalzheimersdisease |