Long-term memory encoding engram neurons are established by the transcriptional cycling

While long-term memory (LTM) is known to be encoded in specific neural cells, engram neurons, it has been unclear how these engram neurons are formed during training. In Drosophila, aversive olfactory LTM is formed by repetitive training trials with rest intervals between training trial, spaced training.

Drosophila can formed Long-term memory (LTM) by repetitive training trials with rest intervals. In the neurons to which information is input, MAPK(1) activates transcription factor CREB(2) by training with an interval, and expresses c-fos(3). c-fos is also a transcription factor, which is activated by MAPK and expresses CREB. By repeating training, it became clear that a transcription cycle such as c-fos expressing CREB and CREB expressing c-fos was formed. Engram cells with high expression level of CREB were formed. In this way, it was revealed that neuronal cells with high expression of CREB were born, and this cell became engram cells. This result is expected not only to elucidate the mechanism of improving the effect of learning, establishment of memory by efficient learning, but also to be useful for the treatment of memory impairment.

MAPK (mitogen activated protein kinase)

One of protein kinase. It is also used as a generic term for the MAPK family (ERK, JNK, p38 etc). MAPK activity is necessary for long-term memory formation.

CREB (cAMP response element binding protein)

One of the transcription factors. Genes essential for long-term memory formation. Controls gene expression necessary for memory formation.


One of the transcription factors. One of the earliest genes that is expressed downstream of CREB.

By repetitive learning at intervals, MAPK is activated in the nerve cells to which repetitive information is input, so that a transcription cycle of CREB and c-fos is formed. In the nerve cells in which the transcription cycle is formed, the amount of CREB increases and it becomes an engram cell in which long-term memory is formed.


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