Impaired theta and low-gamma directed information flow in the hippocampal-prefrontal circuit underlies working memory deficits in APP/PS1 mice
Abstract Alzheimer’s disease (AD) is a progressive neurodegenerative disorder characterized by cognitive decline. Working memory impairment, a hallmark of early-stage AD, is hypothesized to arise from deficits in encoding processes. Given the critical role of hippocampal-prefrontal interactions in w...
Saved in:
| Main Authors: | , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
BMC
2025-07-01
|
| Series: | Behavioral and Brain Functions |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12993-025-00285-y |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1849238265484279808 |
|---|---|
| author | Hongrui Ai Shengnan Zhang Chengbo Si Tiaotiao Liu Xuyuan Zheng Xin Tian Wenwen Bai |
| author_facet | Hongrui Ai Shengnan Zhang Chengbo Si Tiaotiao Liu Xuyuan Zheng Xin Tian Wenwen Bai |
| author_sort | Hongrui Ai |
| collection | DOAJ |
| description | Abstract Alzheimer’s disease (AD) is a progressive neurodegenerative disorder characterized by cognitive decline. Working memory impairment, a hallmark of early-stage AD, is hypothesized to arise from deficits in encoding processes. Given the critical role of hippocampal-prefrontal interactions in working memory, we investigated whether disrupted encoding mechanisms in this circuit contribute to AD-related deficits. We performed simultaneous local field potential (LFP) recordings in the ventral hippocampus (vHPC) and medial prefrontal cortex (mPFC) of APP/PS1 transgenic mice during a spatial working memory task. We analyzed oscillatory dynamics and directed information flow between these two regions across distinct task phases. Wild-type mice exhibited task-phase-specific enhancement of theta (4–12 Hz) and low-gamma (30–40 Hz) information flow from vHPC to mPFC during encoding, which correlated with performance accuracy. APP/PS1 mice showed a significant reduction in the theta and low-gamma flow and impaired task performance. Decoding analyses revealed a robust correlation between the strength of directed information flow and performance accuracy. These findings provide compelling evidence for a neurophysiological mechanism linking vHPC-mPFC circuit dynamics to encoding processes, offering new insights into the neural basis of working memory impairment in AD. |
| format | Article |
| id | doaj-art-efc0c6c47c7d49b2a992979d6843f68d |
| institution | Kabale University |
| issn | 1744-9081 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | BMC |
| record_format | Article |
| series | Behavioral and Brain Functions |
| spelling | doaj-art-efc0c6c47c7d49b2a992979d6843f68d2025-08-20T04:01:41ZengBMCBehavioral and Brain Functions1744-90812025-07-0121111710.1186/s12993-025-00285-yImpaired theta and low-gamma directed information flow in the hippocampal-prefrontal circuit underlies working memory deficits in APP/PS1 miceHongrui Ai0Shengnan Zhang1Chengbo Si2Tiaotiao Liu3Xuyuan Zheng4Xin Tian5Wenwen Bai6School of Biomedical Engineering and Technology, Tianjin Medical UniversitySchool of Biomedical Engineering and Technology, Tianjin Medical UniversitySchool of Biomedical Engineering and Technology, Tianjin Medical UniversitySchool of Biomedical Engineering and Technology, Tianjin Medical UniversitySchool of Biomedical Engineering and Technology, Tianjin Medical UniversitySchool of Biomedical Engineering and Technology, Tianjin Medical UniversitySchool of Biomedical Engineering and Technology, Tianjin Medical UniversityAbstract Alzheimer’s disease (AD) is a progressive neurodegenerative disorder characterized by cognitive decline. Working memory impairment, a hallmark of early-stage AD, is hypothesized to arise from deficits in encoding processes. Given the critical role of hippocampal-prefrontal interactions in working memory, we investigated whether disrupted encoding mechanisms in this circuit contribute to AD-related deficits. We performed simultaneous local field potential (LFP) recordings in the ventral hippocampus (vHPC) and medial prefrontal cortex (mPFC) of APP/PS1 transgenic mice during a spatial working memory task. We analyzed oscillatory dynamics and directed information flow between these two regions across distinct task phases. Wild-type mice exhibited task-phase-specific enhancement of theta (4–12 Hz) and low-gamma (30–40 Hz) information flow from vHPC to mPFC during encoding, which correlated with performance accuracy. APP/PS1 mice showed a significant reduction in the theta and low-gamma flow and impaired task performance. Decoding analyses revealed a robust correlation between the strength of directed information flow and performance accuracy. These findings provide compelling evidence for a neurophysiological mechanism linking vHPC-mPFC circuit dynamics to encoding processes, offering new insights into the neural basis of working memory impairment in AD.https://doi.org/10.1186/s12993-025-00285-yAlzheimer’s diseaseWorking memoryEncoding phaseHippocampal-prefrontal circuit |
| spellingShingle | Hongrui Ai Shengnan Zhang Chengbo Si Tiaotiao Liu Xuyuan Zheng Xin Tian Wenwen Bai Impaired theta and low-gamma directed information flow in the hippocampal-prefrontal circuit underlies working memory deficits in APP/PS1 mice Behavioral and Brain Functions Alzheimer’s disease Working memory Encoding phase Hippocampal-prefrontal circuit |
| title | Impaired theta and low-gamma directed information flow in the hippocampal-prefrontal circuit underlies working memory deficits in APP/PS1 mice |
| title_full | Impaired theta and low-gamma directed information flow in the hippocampal-prefrontal circuit underlies working memory deficits in APP/PS1 mice |
| title_fullStr | Impaired theta and low-gamma directed information flow in the hippocampal-prefrontal circuit underlies working memory deficits in APP/PS1 mice |
| title_full_unstemmed | Impaired theta and low-gamma directed information flow in the hippocampal-prefrontal circuit underlies working memory deficits in APP/PS1 mice |
| title_short | Impaired theta and low-gamma directed information flow in the hippocampal-prefrontal circuit underlies working memory deficits in APP/PS1 mice |
| title_sort | impaired theta and low gamma directed information flow in the hippocampal prefrontal circuit underlies working memory deficits in app ps1 mice |
| topic | Alzheimer’s disease Working memory Encoding phase Hippocampal-prefrontal circuit |
| url | https://doi.org/10.1186/s12993-025-00285-y |
| work_keys_str_mv | AT hongruiai impairedthetaandlowgammadirectedinformationflowinthehippocampalprefrontalcircuitunderliesworkingmemorydeficitsinappps1mice AT shengnanzhang impairedthetaandlowgammadirectedinformationflowinthehippocampalprefrontalcircuitunderliesworkingmemorydeficitsinappps1mice AT chengbosi impairedthetaandlowgammadirectedinformationflowinthehippocampalprefrontalcircuitunderliesworkingmemorydeficitsinappps1mice AT tiaotiaoliu impairedthetaandlowgammadirectedinformationflowinthehippocampalprefrontalcircuitunderliesworkingmemorydeficitsinappps1mice AT xuyuanzheng impairedthetaandlowgammadirectedinformationflowinthehippocampalprefrontalcircuitunderliesworkingmemorydeficitsinappps1mice AT xintian impairedthetaandlowgammadirectedinformationflowinthehippocampalprefrontalcircuitunderliesworkingmemorydeficitsinappps1mice AT wenwenbai impairedthetaandlowgammadirectedinformationflowinthehippocampalprefrontalcircuitunderliesworkingmemorydeficitsinappps1mice |