Identification and manipulation of a subset of hippocampal cells that are active during memory formation
Recent research coming out of the Tonegawa lab at MIT has provided evidence that memories actually reside in specific neural ensembles- suggested to be the cellular correlates of memory engrams (i.e. memory trace) by showing that the activation of a subset of neurons involved during learning is sufficient to re-instate memory recall.
Specifically, they combined an inducible and activity-dependent system with optogenetics to label and stimulate hippocampal dentate gyrus (DG) cells that were active only during memory formation and found that they could express the light-sensitive ion channel channelrhodospin-2 (ChR2) during defined periods of an animal’s life and only in an active subset of DG cells. Moreover, they found that exposure to tasks known to engage the hippocampus, such as open field exploration and fear conditioning, dramatically increased the number of cells expressing ChR2. Notably, two independent populations of DG cells were recruited differentially to code for two distinct environments. Finally, they were able to demonstrate optical stimulation (i.e. via shining blue light) of DG cells active during fear memory formation was sufficient to activate fear memory recall in a context-specific manner. The number of light-activated cells positively correlated with the strength of fear memory expression, and optical stimulation of the DG was also sufficient to activate downstream regions thought to be involved in fear memory recall.
This work was presented today at the 2012 Society for Neuroscience Annual Meeting via a posters titled Optogenetic Tagging and Manipulation of Hippocampal Memory Engrams and Optogenetic Activation of a Memory Engram and was published earlier this year in Nature.
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