3:09 PM
Mar 12, 2018
 |  BC Extra  |  Preclinical News

Releasing molecular brake may improve memory recall in PTSD, aging

A study published in Nature Medicine suggests releasing a "molecular brake" between memory stimulating and memory retrieving regions of the hippocampus could offer a new therapeutic strategy to improve memory recall in post-traumatic stress disorder and aging.

Time-dependent memory generalization, or the loss of specific details over time, is a characteristic of PTSD and age-related cognitive impairment. Multiple studies have shown that the hippocampus plays a role in maintaining the specificity of memories.

Previously, the group from Massachusetts General Hospital and colleagues identified an age-related decrease in inhibitory connections made between dentate gyrus cells (DGCs) -- cells that help create memories -- and the CA3 region -- which helps store memories for retrieval -- of the hippocampus. Separate studies have shown that lack of inhibition of CA3 leads to imprecise memory recall. It was unclear, however, whether modulating the DGC-CA3 connection could directly improve memory precision.

In this study, a series of in vitro and bioinformatic screens suggested that actin binding LIM protein family member 3 (ABLIM3) expression may prevent inhibitory connections between DGCs and the CA3 region.

The researchers confirmed in healthy mice that ABLIM3 knockdown in DGCs increased inhibitory signals to CA3 neurons and decreased the excitation-inhibition ratio in the neurons compared with normal ABLIM3 expression.

In long-term behavioral experiments with initial exposure to a fear-inducing scenario, mice with ABLIM3 knockdown in DGCs were better able to differentiate between a fear-inducing scenario and a neutral scenario, and had increased DGC-CA3 connectivity after initial exposure, than mice with normal ABLIM3 expression.

The same intervention yielded similar results in a mouse model of age-related cognitive impairment. The results suggest that decreasing ABLIM3 can remove the brake between DGCs and the CA3 region and help improve memory precision.

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