Distinct changes to hippocampal and medial entorhinal circuits emerge across the progression of cognitive deficits in epilepsy
Summary: Temporal lobe epilepsy (TLE) causes pervasive and progressive memory impairments, yet the specific circuit changes that drive these deficits remain unclear. To investigate how hippocampal-entorhinal dysfunction contributes to progressive memory deficits in epilepsy, we performed simultaneou...
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| Language: | English |
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Elsevier
2025-02-01
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124724014827 |
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| author | Yu Feng Keziah S. Diego Zhe Dong Zoé Christenson Wick Lucia Page-Harley Veronica Page-Harley Julia Schnipper Sophia I. Lamsifer Zachary T. Pennington Lauren M. Vetere Paul A. Philipsberg Ivan Soler Albert Jurkowski Christin J. Rosado Nadia N. Khan Denise J. Cai Tristan Shuman |
| author_facet | Yu Feng Keziah S. Diego Zhe Dong Zoé Christenson Wick Lucia Page-Harley Veronica Page-Harley Julia Schnipper Sophia I. Lamsifer Zachary T. Pennington Lauren M. Vetere Paul A. Philipsberg Ivan Soler Albert Jurkowski Christin J. Rosado Nadia N. Khan Denise J. Cai Tristan Shuman |
| author_sort | Yu Feng |
| collection | DOAJ |
| description | Summary: Temporal lobe epilepsy (TLE) causes pervasive and progressive memory impairments, yet the specific circuit changes that drive these deficits remain unclear. To investigate how hippocampal-entorhinal dysfunction contributes to progressive memory deficits in epilepsy, we performed simultaneous in vivo electrophysiology in the hippocampus (HPC) and medial entorhinal cortex (MEC) of control and epileptic mice 3 or 8 weeks after pilocarpine-induced status epilepticus (Pilo-SE). We found that HPC synchronization deficits (including reduced theta power, coherence, and altered interneuron spike timing) emerged within 3 weeks of Pilo-SE, aligning with early-onset, relatively subtle memory deficits. In contrast, abnormal synchronization within the MEC and between HPC and MEC emerged later, by 8 weeks after Pilo-SE, when spatial memory impairment was more severe. Furthermore, a distinct subpopulation of MEC layer 3 excitatory neurons (active at theta troughs) was specifically impaired in epileptic mice. Together, these findings suggest that hippocampal-entorhinal circuit dysfunction accumulates and shifts as cognitive impairment progresses in TLE. |
| format | Article |
| id | doaj-art-33d27309aabd43eca7506656602f709b |
| institution | Kabale University |
| issn | 2211-1247 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cell Reports |
| spelling | doaj-art-33d27309aabd43eca7506656602f709b2025-01-24T04:44:58ZengElsevierCell Reports2211-12472025-02-01442115131Distinct changes to hippocampal and medial entorhinal circuits emerge across the progression of cognitive deficits in epilepsyYu Feng0Keziah S. Diego1Zhe Dong2Zoé Christenson Wick3Lucia Page-Harley4Veronica Page-Harley5Julia Schnipper6Sophia I. Lamsifer7Zachary T. Pennington8Lauren M. Vetere9Paul A. Philipsberg10Ivan Soler11Albert Jurkowski12Christin J. Rosado13Nadia N. Khan14Denise J. Cai15Tristan Shuman16Nash Family Department of Neuroscience, The Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USANash Family Department of Neuroscience, The Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USANash Family Department of Neuroscience, The Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USANash Family Department of Neuroscience, The Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USANash Family Department of Neuroscience, The Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USANash Family Department of Neuroscience, The Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USANash Family Department of Neuroscience, The Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USANash Family Department of Neuroscience, The Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USANash Family Department of Neuroscience, The Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USANash Family Department of Neuroscience, The Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USANash Family Department of Neuroscience, The Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USANash Family Department of Neuroscience, The Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USANash Family Department of Neuroscience, The Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USANash Family Department of Neuroscience, The Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USANash Family Department of Neuroscience, The Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USANash Family Department of Neuroscience, The Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USANash Family Department of Neuroscience, The Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA; Corresponding authorSummary: Temporal lobe epilepsy (TLE) causes pervasive and progressive memory impairments, yet the specific circuit changes that drive these deficits remain unclear. To investigate how hippocampal-entorhinal dysfunction contributes to progressive memory deficits in epilepsy, we performed simultaneous in vivo electrophysiology in the hippocampus (HPC) and medial entorhinal cortex (MEC) of control and epileptic mice 3 or 8 weeks after pilocarpine-induced status epilepticus (Pilo-SE). We found that HPC synchronization deficits (including reduced theta power, coherence, and altered interneuron spike timing) emerged within 3 weeks of Pilo-SE, aligning with early-onset, relatively subtle memory deficits. In contrast, abnormal synchronization within the MEC and between HPC and MEC emerged later, by 8 weeks after Pilo-SE, when spatial memory impairment was more severe. Furthermore, a distinct subpopulation of MEC layer 3 excitatory neurons (active at theta troughs) was specifically impaired in epileptic mice. Together, these findings suggest that hippocampal-entorhinal circuit dysfunction accumulates and shifts as cognitive impairment progresses in TLE.http://www.sciencedirect.com/science/article/pii/S2211124724014827CP: Neuroscience |
| spellingShingle | Yu Feng Keziah S. Diego Zhe Dong Zoé Christenson Wick Lucia Page-Harley Veronica Page-Harley Julia Schnipper Sophia I. Lamsifer Zachary T. Pennington Lauren M. Vetere Paul A. Philipsberg Ivan Soler Albert Jurkowski Christin J. Rosado Nadia N. Khan Denise J. Cai Tristan Shuman Distinct changes to hippocampal and medial entorhinal circuits emerge across the progression of cognitive deficits in epilepsy Cell Reports CP: Neuroscience |
| title | Distinct changes to hippocampal and medial entorhinal circuits emerge across the progression of cognitive deficits in epilepsy |
| title_full | Distinct changes to hippocampal and medial entorhinal circuits emerge across the progression of cognitive deficits in epilepsy |
| title_fullStr | Distinct changes to hippocampal and medial entorhinal circuits emerge across the progression of cognitive deficits in epilepsy |
| title_full_unstemmed | Distinct changes to hippocampal and medial entorhinal circuits emerge across the progression of cognitive deficits in epilepsy |
| title_short | Distinct changes to hippocampal and medial entorhinal circuits emerge across the progression of cognitive deficits in epilepsy |
| title_sort | distinct changes to hippocampal and medial entorhinal circuits emerge across the progression of cognitive deficits in epilepsy |
| topic | CP: Neuroscience |
| url | http://www.sciencedirect.com/science/article/pii/S2211124724014827 |
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