Activity disruption causes degeneration of entorhinal neurons in a mouse model of Alzheimer’s circuit dysfunction
Neurodegenerative diseases are characterized by selective vulnerability of distinct cell populations; however, the cause for this specificity remains elusive. Here, we show that entorhinal cortex layer 2 (EC2) neurons are unusually vulnerable to prolonged neuronal inactivity compared with neighborin...
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| Format: | Article |
| Language: | English |
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eLife Sciences Publications Ltd
2022-12-01
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| Series: | eLife |
| Subjects: | |
| Online Access: | https://elifesciences.org/articles/83813 |
| _version_ | 1797944685034995712 |
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| author | Rong Zhao Stacy D Grunke Caleb A Wood Gabriella A Perez Melissa Comstock Ming-Hua Li Anand K Singh Kyung-Won Park Joanna L Jankowsky |
| author_facet | Rong Zhao Stacy D Grunke Caleb A Wood Gabriella A Perez Melissa Comstock Ming-Hua Li Anand K Singh Kyung-Won Park Joanna L Jankowsky |
| author_sort | Rong Zhao |
| collection | DOAJ |
| description | Neurodegenerative diseases are characterized by selective vulnerability of distinct cell populations; however, the cause for this specificity remains elusive. Here, we show that entorhinal cortex layer 2 (EC2) neurons are unusually vulnerable to prolonged neuronal inactivity compared with neighboring regions of the temporal lobe, and that reelin + stellate cells connecting EC with the hippocampus are preferentially susceptible within the EC2 population. We demonstrate that neuronal death after silencing can be elicited through multiple independent means of activity inhibition, and that preventing synaptic release, either alone or in combination with electrical shunting, is sufficient to elicit silencing-induced degeneration. Finally, we discovered that degeneration following synaptic silencing is governed by competition between active and inactive cells, which is a circuit refinement process traditionally thought to end early in postnatal life. Our data suggests that the developmental window for wholesale circuit plasticity may extend into adulthood for specific brain regions. We speculate that this sustained potential for remodeling by entorhinal neurons may support lifelong memory but renders them vulnerable to prolonged activity changes in disease. |
| first_indexed | 2024-04-10T20:43:32Z |
| format | Article |
| id | doaj.art-3fdef3d02f1d43b89c3fd6523fe9841c |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-04-10T20:43:32Z |
| publishDate | 2022-12-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj.art-3fdef3d02f1d43b89c3fd6523fe9841c2023-01-24T13:00:52ZengeLife Sciences Publications LtdeLife2050-084X2022-12-011110.7554/eLife.83813Activity disruption causes degeneration of entorhinal neurons in a mouse model of Alzheimer’s circuit dysfunctionRong Zhao0Stacy D Grunke1Caleb A Wood2https://orcid.org/0000-0002-3320-0485Gabriella A Perez3Melissa Comstock4Ming-Hua Li5Anand K Singh6Kyung-Won Park7Joanna L Jankowsky8https://orcid.org/0000-0002-5593-2310Department of Neuroscience, Huffington Center on Aging, Baylor College of Medicine, Houston, United StatesDepartment of Neuroscience, Huffington Center on Aging, Baylor College of Medicine, Houston, United StatesDepartment of Neuroscience, Huffington Center on Aging, Baylor College of Medicine, Houston, United StatesDepartment of Neuroscience, Huffington Center on Aging, Baylor College of Medicine, Houston, United StatesDepartment of Neuroscience, Huffington Center on Aging, Baylor College of Medicine, Houston, United StatesDepartment of Neuroscience, Huffington Center on Aging, Baylor College of Medicine, Houston, United StatesDepartment of Neuroscience, Huffington Center on Aging, Baylor College of Medicine, Houston, United StatesDepartment of Neuroscience, Huffington Center on Aging, Baylor College of Medicine, Houston, United StatesDepartment of Neuroscience, Huffington Center on Aging, Baylor College of Medicine, Houston, United States; Departments of Neurology, Neurosurgery, and Molecular and Cellular Biology, Huffington Center on Aging, Baylor College of Medicine, Houston, United StatesNeurodegenerative diseases are characterized by selective vulnerability of distinct cell populations; however, the cause for this specificity remains elusive. Here, we show that entorhinal cortex layer 2 (EC2) neurons are unusually vulnerable to prolonged neuronal inactivity compared with neighboring regions of the temporal lobe, and that reelin + stellate cells connecting EC with the hippocampus are preferentially susceptible within the EC2 population. We demonstrate that neuronal death after silencing can be elicited through multiple independent means of activity inhibition, and that preventing synaptic release, either alone or in combination with electrical shunting, is sufficient to elicit silencing-induced degeneration. Finally, we discovered that degeneration following synaptic silencing is governed by competition between active and inactive cells, which is a circuit refinement process traditionally thought to end early in postnatal life. Our data suggests that the developmental window for wholesale circuit plasticity may extend into adulthood for specific brain regions. We speculate that this sustained potential for remodeling by entorhinal neurons may support lifelong memory but renders them vulnerable to prolonged activity changes in disease.https://elifesciences.org/articles/83813selective vulnerabilityentorhinal cortexchemogenetic silencingactivity-dependent competitioncircuit plasticityAlzheimer's disease |
| spellingShingle | Rong Zhao Stacy D Grunke Caleb A Wood Gabriella A Perez Melissa Comstock Ming-Hua Li Anand K Singh Kyung-Won Park Joanna L Jankowsky Activity disruption causes degeneration of entorhinal neurons in a mouse model of Alzheimer’s circuit dysfunction eLife selective vulnerability entorhinal cortex chemogenetic silencing activity-dependent competition circuit plasticity Alzheimer's disease |
| title | Activity disruption causes degeneration of entorhinal neurons in a mouse model of Alzheimer’s circuit dysfunction |
| title_full | Activity disruption causes degeneration of entorhinal neurons in a mouse model of Alzheimer’s circuit dysfunction |
| title_fullStr | Activity disruption causes degeneration of entorhinal neurons in a mouse model of Alzheimer’s circuit dysfunction |
| title_full_unstemmed | Activity disruption causes degeneration of entorhinal neurons in a mouse model of Alzheimer’s circuit dysfunction |
| title_short | Activity disruption causes degeneration of entorhinal neurons in a mouse model of Alzheimer’s circuit dysfunction |
| title_sort | activity disruption causes degeneration of entorhinal neurons in a mouse model of alzheimer s circuit dysfunction |
| topic | selective vulnerability entorhinal cortex chemogenetic silencing activity-dependent competition circuit plasticity Alzheimer's disease |
| url | https://elifesciences.org/articles/83813 |
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