Memory retrieval by activating engram cells in mouse models of early Alzheimer’s disease
Alzheimer’s disease (AD) is a neurodegenerative disorder characterized by progressive memory decline and subsequent loss of broader cognitive functions. Memory decline in the early stages of AD is mostly limited to episodic memory, for which the hippocampus has a crucial role. However, it has been u...
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| Format: | Article |
| Language: | en_US |
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Nature Publishing Group
2017
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| Online Access: | http://hdl.handle.net/1721.1/109332 https://orcid.org/0000-0002-5218-1216 https://orcid.org/0000-0003-0121-8514 https://orcid.org/0000-0003-2839-8228 |
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| author | Roy, Dheeraj Arons, Autumn Mitchell, Teryn Pignatelli di Spinazzola, Michele Ryan, Tomas John Tonegawa, Susumu |
| author2 | Massachusetts Institute of Technology. Department of Biology |
| author_facet | Massachusetts Institute of Technology. Department of Biology Roy, Dheeraj Arons, Autumn Mitchell, Teryn Pignatelli di Spinazzola, Michele Ryan, Tomas John Tonegawa, Susumu |
| author_sort | Roy, Dheeraj |
| collection | MIT |
| description | Alzheimer’s disease (AD) is a neurodegenerative disorder characterized by progressive memory decline and subsequent loss of broader cognitive functions. Memory decline in the early stages of AD is mostly limited to episodic memory, for which the hippocampus has a crucial role. However, it has been uncertain whether the observed amnesia in the early stages of AD is due to disrupted encoding and consolidation of episodic information, or an impairment in the retrieval of stored memory information. Here we show that in transgenic mouse models of early AD, direct optogenetic activation of hippocampal memory engram cells results in memory retrieval despite the fact that these mice are amnesic in long-term memory tests when natural recall cues are used, revealing a retrieval, rather than a storage impairment. Before amyloid plaque deposition, the amnesia in these mice is age-dependent, which correlates with a progressive reduction in spine density of hippocampal dentate gyrus engram cells. We show that optogenetic induction of long-term potentiation at perforant path synapses of dentate gyrus engram cells restores both spine density and long-term memory. We also demonstrate that an ablation of dentate gyrus engram cells containing restored spine density prevents the rescue of long-term memory. Thus, selective rescue of spine density in engram cells may lead to an effective strategy for treating memory loss in the early stages of AD. |
| first_indexed | 2024-09-23T16:52:53Z |
| format | Article |
| id | mit-1721.1/109332 |
| institution | Massachusetts Institute of Technology |
| language | en_US |
| last_indexed | 2024-09-23T16:52:53Z |
| publishDate | 2017 |
| publisher | Nature Publishing Group |
| record_format | dspace |
| spelling | mit-1721.1/1093322022-10-03T08:54:22Z Memory retrieval by activating engram cells in mouse models of early Alzheimer’s disease Roy, Dheeraj Arons, Autumn Mitchell, Teryn Pignatelli di Spinazzola, Michele Ryan, Tomas John Tonegawa, Susumu Massachusetts Institute of Technology. Department of Biology Massachusetts Institute of Technology. Department of Brain and Cognitive Sciences Picower Institute for Learning and Memory RIKEN-MIT Center for Neural Circuit Genetics Roy, Dheeraj Arons, Autumn Mitchell, Teryn Pignatelli di Spinazzola, Michele Ryan, Tomas John Tonegawa, Susumu Alzheimer’s disease (AD) is a neurodegenerative disorder characterized by progressive memory decline and subsequent loss of broader cognitive functions. Memory decline in the early stages of AD is mostly limited to episodic memory, for which the hippocampus has a crucial role. However, it has been uncertain whether the observed amnesia in the early stages of AD is due to disrupted encoding and consolidation of episodic information, or an impairment in the retrieval of stored memory information. Here we show that in transgenic mouse models of early AD, direct optogenetic activation of hippocampal memory engram cells results in memory retrieval despite the fact that these mice are amnesic in long-term memory tests when natural recall cues are used, revealing a retrieval, rather than a storage impairment. Before amyloid plaque deposition, the amnesia in these mice is age-dependent, which correlates with a progressive reduction in spine density of hippocampal dentate gyrus engram cells. We show that optogenetic induction of long-term potentiation at perforant path synapses of dentate gyrus engram cells restores both spine density and long-term memory. We also demonstrate that an ablation of dentate gyrus engram cells containing restored spine density prevents the rescue of long-term memory. Thus, selective rescue of spine density in engram cells may lead to an effective strategy for treating memory loss in the early stages of AD. RIKEN Brain Science Institute Howard Hughes Medical Institute JPB Foundation 2017-05-24T20:35:53Z 2017-05-24T20:35:53Z 2016-03 2015-08 Article http://purl.org/eprint/type/JournalArticle 0028-0836 1476-4687 http://hdl.handle.net/1721.1/109332 Roy, Dheeraj S. et al. “Memory Retrieval by Activating Engram Cells in Mouse Models of Early Alzheimer’s Disease.” Nature 531.7595 (2016): 508–512. https://orcid.org/0000-0002-5218-1216 https://orcid.org/0000-0003-0121-8514 https://orcid.org/0000-0003-2839-8228 en_US http://dx.doi.org/10.1038/nature17172 Nature Article is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use. application/pdf Nature Publishing Group PMC |
| spellingShingle | Roy, Dheeraj Arons, Autumn Mitchell, Teryn Pignatelli di Spinazzola, Michele Ryan, Tomas John Tonegawa, Susumu Memory retrieval by activating engram cells in mouse models of early Alzheimer’s disease |
| title | Memory retrieval by activating engram cells in mouse models of early Alzheimer’s disease |
| title_full | Memory retrieval by activating engram cells in mouse models of early Alzheimer’s disease |
| title_fullStr | Memory retrieval by activating engram cells in mouse models of early Alzheimer’s disease |
| title_full_unstemmed | Memory retrieval by activating engram cells in mouse models of early Alzheimer’s disease |
| title_short | Memory retrieval by activating engram cells in mouse models of early Alzheimer’s disease |
| title_sort | memory retrieval by activating engram cells in mouse models of early alzheimer s disease |
| url | http://hdl.handle.net/1721.1/109332 https://orcid.org/0000-0002-5218-1216 https://orcid.org/0000-0003-0121-8514 https://orcid.org/0000-0003-2839-8228 |
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