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. 2022 Mar 26;298(5):101866. doi: 10.1016/j.jbc.2022.101866

Figure 1.

Figure 1

Engram labeling technology. (1) The immediate early gene c-fos promoter drives the expression of tTA. Doxycycline (DOX), delivered through diet, prevents tTA-TRE element binding. (2) An electric shock is delivered when the animal is in a particular context (context A). An engram for that episodic experience is formed (purple cells). In the absence of DOX, engram neurons that are active during the encoding of that fear memory express channelrhodopsin-2 (ChR2) transgene and GFP reporter. (3) Return to context A will reactivate the engram and will induce a freezing response in the animal—behavior associated with fear. (4) The engram cells tagged with ChR2 can be optogenetically reactivated by delivering light into the brain of the animal. This artificial recall of the memory induces freezing behavior in the animal in a neutral context B. TRE, tetracycline response element; tTA, tetracycline transactivator.