Thursday, 26 April 2012

Towards an artificial engram

Liu X, Ramirez S, Pang PT, Puryear CB, Govindarajan A, Deisseroth K, Tonegawa S (2012) Optogenetic stimulation of a hippocampal engram activates fear memory recall. Nature.

Tim Bliss and friends recently wrote about the possibilities of using fancy genetic tools to test the hypothesis (quite an old hypothesis too) that memories are encoded in networks of neurons whose synapses have been modified by LTP-like plasticity (Neves, Cooke & Bliss, Nat. Rev. Neurosci. 2008). This week's Nature has a remarkable paper from the Tonegawa group, where they have made a big step forward along this path. They used a clever combination of transgenic mice and virus transfection techniques to produce a mouse where activated neurons in the dentate gyrus (DG) of the hippocampus are not only labelled with YFP but also (and here's the powerful bit) express light activated sodium channels (ChR2). They found that fear conditioning labelled a subset of neurons in the DG, and what's more, that activating this set of neurons a few days later (by shining blue light into the hippocampus), even in a different context to the original conditioning, produced the freezing reaction that you see in fear conditioning.

So, a significant step forward in the quest for the engram. It's interesting to ponder how accurately this result reflects how memory operates in the intact animal. You might expect that more than the DG is involved, for example. Would it be possible to do similar experiments with similar results in CA1 or CA3? And what about other forms of memory, such as episodic memory, would they work in a similar way?