Memory engram storage and retrieval. Tonegawa, et al. (2015)

In my first post, in a long, loooooong time, I’ve decided to join the #366papers group on Twitter and read a paper every day (due to the vacations recently booked, I know I’ll fail). I figured to keep this blog alive and to keep me writing something other than grants, I would post short, daily reviews, and perhaps longer reviews after finishing a group of papers. I’ll likely revisit papers multiple times as I learn more. I’m interested to see how my analyses will change with time. So here, I’ll start with a review on a topic I find very exciting: the identification of memory engrams.

Citation: Tonegawa, et al. (2015). Memory engram and retrieval. Current Opinion in Neurobiology, 35:101-109.

                This paper reviews recent experiments on the newly developed technology of “memory engram” (also known as “memory trace”) labeling. That is, we are now able to label cells active during the processing of a particular memory. Further, we can express specifically in these cells channelrhodopsins which can be activated by light to stimulate or inhibit neural activity, known as optogenetics.

                In particular, the focus of this review is on recent studies dissociating the multiple processes involved in memory. For instance, it has long been suggested that Hebbian synaptic plasticity, a process whereby activity will strengthen a synapse, is responsible for retaining information in nervous systems. The authors discuss a recent study that shows how merely the connectivity of a nervous system as complex as a mammal’s is suitable for the storage of a memory, while plasticity underlies the consolidation component of the memory engram.

                Further the authors note that memories are distributed across a particular sequential circuit. If a particular memory consists of cells A>B>C>D>E, and you inhibit the activity of cell B, but artificially stimulate cell D, the memory can still be successfully retrieved. The authors note how it is of interest to identify all of the cells brainwide involved in particular engrams. I wondered how far upstream one could stimulate an engram cell to result in memory retrieval. I find it highly unlikely that stimulation in early sensory areas will result in recall, as these cells are likely to be involved in many memory traces in addition to current sensory processing. As has been shown (in a classic paper that I’ll write up another day), stimulation of engram cells in the dentate gyrus (DG) of the hippocampus results in recall of that memory specifically. Theoretically, the DG serves as an orthogonalizer of new memories, whereby the process of adult neurogenesis serves to constantly generate new population codes resulting in new, separate memory traces. So it may be that it is here where we would consider a memory trace to start, but it is perhaps possible that stimulating upstream regions such as the entorhinal cortex is enough to evoke recall, at least before more new neurons integrate into an ever-changing circuit. Currently, I know very little about memory processing downstream from the hippocampus, so the downstream extent of a memory trace is a complete mystery to me.

                As this is a very interesting topic with tons of recent findings, the next few reviews will also focus on techniques and findings related to memory traces.


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