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Press Release
March 17, 2016
Light stimulation of brain cells can recover memories in mice with Alzheimer's disease-like memory loss, according to new research from the RIKEN-MIT Center for Neural Circuit Genetics. The rescue of memories, which changed both the structure of neurons as well as the behavior of mice, was achieved using optogenetics, a method for manipulating genetically tagged cells with precise bursts of light. This finding suggests that impaired retrieval of memories, rather than poor storage or encoding, may underlie this prominent symptom of early Alzheimer's disease and points to the synaptic connectivity between memory cells as being crucial for retrieval.
Loss of long-term memory for specific learned experiences is a hallmark of early Alzheimer's disease (AD) that is also exhibited by mice genetically engineered to develop AD-like symptoms. Building on their previous work that identified and activated memory cells, a group led by RIKEN Brain Science Institute and RIKEN-MIT Center Director Susumu Tonegawa has now shown that spines — small knobs on brain-cell dendrites through which synaptic connections are formed — are essential for memory retrieval in these AD mice. spines. Previous work had shown that spines grow when neurons undergo long-term potentiation, a persistent strengthening of synaptic connectivity that happens naturally in the brain but can also be artificially induced through stimulation.
Through repeated stimulation with high-frequency bursts of light to the hippocampal memory circuit in AD mice, the team was able to boost the number of spines to levels indistinguishable from those in control mice. The freezing behavior in the trained task also returned and remained for up to six days. The implication is that restoring lost spines in the hippocampal circuit facilitated retrieval of the specific fear experience and its associated freezing behavior. “We have shown for the first time that increasing synaptic connectivity within engram cell circuits can be used to treat memory loss in mouse models of early Alzheimer’s disease,” says lead author Dheeraj Roy.
Light stimulation did not boost the number of spines in normal mice or strengthen the fear memory, nor did indiscriminately shining light in the dentate gyrus result in any long-term memory improvement. Only the precise stimulation of engram cells was able to increase the number of spines and bring about the memory improvement in AD mice.
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