“Alzheimer’s disease is a neurodegenerative disorder characterized by progressive memory decline and subsequent loss of broader cognitive functions. Memory decline in the early stages of Alzeimer’s 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 Alzeimer’s is due to disrupted encoding and consolidation of episodic information, or an impairment in the retrieval of stored memory information. Here [the authors] show that in transgenic mouse models of early Alzeimer’s, 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. [The authors] 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. [They] also demonstrate that an ablation of dentate gyrus engram cells containing restored spine density prevents the rescue of long-term memory. Thus, [they suggest that] selective rescue of spine density in engram cells may lead to an effective strategy for treating memory loss in the early stages of AD.”
Roy DS, Arons A, Mitchell TI, Pignatelli M, Ryan TJ and Tonegawa S: Memory retrieval by activating engram cells in mouse models of early Alzheimer’s disease. Nature [Epub ahead of print, March 16, 2016; doi: 10.1038/nature17172].

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