A novel paradigm for assessing olfactory working memory capacity in mice
Abstract A decline in working memory (WM) capacity is suggested to be one of the earliest symptoms observed in Alzheimer’s disease (AD). Although WM capacity is widely studied in healthy subjects and neuropsychiatric patients, few tasks are developed to measure this variation in rodents. The present...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Nature Publishing Group
2020-12-01
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| Series: | Translational Psychiatry |
| Online Access: | https://doi.org/10.1038/s41398-020-01120-w |
| _version_ | 1818589538424979456 |
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| author | Geng-Di Huang Li-Xin Jiang Feng Su Hua-Li Wang Chen Zhang Xin Yu |
| author_facet | Geng-Di Huang Li-Xin Jiang Feng Su Hua-Li Wang Chen Zhang Xin Yu |
| author_sort | Geng-Di Huang |
| collection | DOAJ |
| description | Abstract A decline in working memory (WM) capacity is suggested to be one of the earliest symptoms observed in Alzheimer’s disease (AD). Although WM capacity is widely studied in healthy subjects and neuropsychiatric patients, few tasks are developed to measure this variation in rodents. The present study describes a novel olfactory working memory capacity (OWMC) task, which assesses the ability of mice to remember multiple odours. The task was divided into five phases: context adaptation, digging training, rule-learning for non-matching to a single-sample odour (NMSS), rule-learning for non-matching to multiple sample odours (NMMS) and capacity testing. During the capacity-testing phase, the WM capacity (number of odours that the mice could remember) remained stable (average capacity ranged from 6.11 to 7.00) across different testing sessions in C57 mice. As the memory load increased, the average errors of each capacity level increased and the percent correct gradually declined to chance level, which suggested a limited OWMC in C57 mice. Then, we assessed the OWMC of 5 × FAD transgenic mice, an animal model of AD. We found that the performance displayed no significant differences between young adult (3-month-old) 5 × FAD mice and wild-type (WT) mice during the NMSS phase and NMMS phase; however, during the capacity test with increasing load, we found that the OWMC of young adult 5 × FAD mice was significantly decreased compared with WT mice, and the average error was significantly increased while the percent correct was significantly reduced, which indicated an impairment of WM capacity at the early stage of AD in the 5 × FAD mice model. Finally, we found that FOS protein levels in the medial prefrontal cortex and entorhinal cortex after the capacity test were significantly lower in 5 × FAD than WT mice. In conclusion, we developed a novel paradigm to assess the capacity of olfactory WM in mice, and we found that OWMC was impaired in the early stage of AD. |
| first_indexed | 2024-12-16T09:42:14Z |
| format | Article |
| id | doaj.art-3b51fdde83b04a3c8cf7d07caaa70399 |
| institution | Directory Open Access Journal |
| issn | 2158-3188 |
| language | English |
| last_indexed | 2024-12-16T09:42:14Z |
| publishDate | 2020-12-01 |
| publisher | Nature Publishing Group |
| record_format | Article |
| series | Translational Psychiatry |
| spelling | doaj.art-3b51fdde83b04a3c8cf7d07caaa703992022-12-21T22:36:14ZengNature Publishing GroupTranslational Psychiatry2158-31882020-12-0110111610.1038/s41398-020-01120-wA novel paradigm for assessing olfactory working memory capacity in miceGeng-Di Huang0Li-Xin Jiang1Feng Su2Hua-Li Wang3Chen Zhang4Xin Yu5Peking University Sixth HospitalPeking University Sixth HospitalPeking-Tsinghua Center for Life Sciences, Academy for Advanced Interdisciplinary Studies, Peking UniversityPeking University Sixth HospitalSchool of Basic Medical Sciences, Beijing Key Laboratory of Neural Regeneration and Repair, Advanced Innovation Center for Human Brain Protection, Capital Medical UniversityPeking University Sixth HospitalAbstract A decline in working memory (WM) capacity is suggested to be one of the earliest symptoms observed in Alzheimer’s disease (AD). Although WM capacity is widely studied in healthy subjects and neuropsychiatric patients, few tasks are developed to measure this variation in rodents. The present study describes a novel olfactory working memory capacity (OWMC) task, which assesses the ability of mice to remember multiple odours. The task was divided into five phases: context adaptation, digging training, rule-learning for non-matching to a single-sample odour (NMSS), rule-learning for non-matching to multiple sample odours (NMMS) and capacity testing. During the capacity-testing phase, the WM capacity (number of odours that the mice could remember) remained stable (average capacity ranged from 6.11 to 7.00) across different testing sessions in C57 mice. As the memory load increased, the average errors of each capacity level increased and the percent correct gradually declined to chance level, which suggested a limited OWMC in C57 mice. Then, we assessed the OWMC of 5 × FAD transgenic mice, an animal model of AD. We found that the performance displayed no significant differences between young adult (3-month-old) 5 × FAD mice and wild-type (WT) mice during the NMSS phase and NMMS phase; however, during the capacity test with increasing load, we found that the OWMC of young adult 5 × FAD mice was significantly decreased compared with WT mice, and the average error was significantly increased while the percent correct was significantly reduced, which indicated an impairment of WM capacity at the early stage of AD in the 5 × FAD mice model. Finally, we found that FOS protein levels in the medial prefrontal cortex and entorhinal cortex after the capacity test were significantly lower in 5 × FAD than WT mice. In conclusion, we developed a novel paradigm to assess the capacity of olfactory WM in mice, and we found that OWMC was impaired in the early stage of AD.https://doi.org/10.1038/s41398-020-01120-w |
| spellingShingle | Geng-Di Huang Li-Xin Jiang Feng Su Hua-Li Wang Chen Zhang Xin Yu A novel paradigm for assessing olfactory working memory capacity in mice Translational Psychiatry |
| title | A novel paradigm for assessing olfactory working memory capacity in mice |
| title_full | A novel paradigm for assessing olfactory working memory capacity in mice |
| title_fullStr | A novel paradigm for assessing olfactory working memory capacity in mice |
| title_full_unstemmed | A novel paradigm for assessing olfactory working memory capacity in mice |
| title_short | A novel paradigm for assessing olfactory working memory capacity in mice |
| title_sort | novel paradigm for assessing olfactory working memory capacity in mice |
| url | https://doi.org/10.1038/s41398-020-01120-w |
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