Importin-7 mediates memory consolidation through regulation of nuclear translocation of training-activated MAPK in Drosophila

Abstract

Translocation of signaling molecules, MAPK in particular, from the cytosol to nucleus represents a universal key element in initiating the gene program that determines memory consolidation. Translocation mechanisms and their behavioral impact, however, remain to be determined. Here, we report that a highly conserved nuclear transporter, Drosophila importin-7 (DIM-7), regulates import of training-activated MAPK for consolidation of long-term memory (LTM). We show that silencing DIM-7 functions results in impaired LTM, whereas overexpression of DIM-7 enhances LTM. This DIM-7-dependent regulation of LTM is confined to a consolidation time window and in mushroom body neurons. Image data show that bidirectional alteration in DIM-7 expression results in proportional changes in the intensity of training-activated MAPK accumulated within the nuclei of mushroom body neurons during LTM consolidation. Such DIM-7-regulated nuclear accumulation of activated MAPK is observed only in the training specified for LTM induction and determines the amplitude, but not the time course, of memory consolidation.long-term memory | consolidation | Drosophila | importin | MAPK

The neural circuit linking mushroom body parallel circuits induces memory consolidation in Drosophila

“…To understand the neural mechanism by which spaced learning induces memory consolidation, we investigated the MB neurons in the flies subjected to olfactory aversive single training or spaced training (3). Previous research has indicated that olfactory training induces the pERK in the nucleus (15), which could map the neurons activated by the training session.…”

Preferential distribution of nuclear MAPK signal in α/β core neurons during long-term memory consolidation in Drosophila

“…According to our previous study (Li et al, 2016 ), we found that LTM training (spaced training, four repeated training sessions with 15-min interval) significantly induces more nuclear translocation of pMAPK at a representative time point of consolidation (8-h after spaced training), compared with naive flies and flies subjected to non-LTM training (massed training, four repeated and consecutive training sessions). This data indicates that LTM training specifically causes pMAPK nuclear translocation in KCs.…”

“…However, relatively slower progress has been made on how behavioral training-induced synaptic signals translocate into nucleus, which is a critical step to bridge the former two questions together. In a recent study, we found that DIM-7, an importin in Drosophila , plays a critical role in mediating nuclear translocation of pMAPK to initiate LTM consolidation (Li et al, 2016 ). In that study, we found that Kenyon cells (KCs), neurons of mushroom body (MB), are critical places for nuclear translocation of pMAPK signal in determining LTM consolidation.…”

“…We first checked the distribution of nuclear pMAPK signal in three major classes of MB neurons (α/β, γ, and α’/β’) at 8-h after spaced training, a representative time point during LTM consolidation (Li et al, 2016 ). To distinguish these classes, we employed three specific Gal4 lines: c739, VT44966, VT57244.…”

Spatial-Memory Formation After Spaced Learning Involves ERKs1/2 Activation Through a Behavioral-Tagging Process

“…Recently, Miyashita et al 22 demonstrated that this ERKs activation is required for the increased expression of c-fos and dCREB2 during spaced training. Moreover, Li et al 45 suggested that translocation of ERKs1/2 to the nucleus of mushroom body neurons is required for the consolidation of this LTM after retraining. ERKs1/2 activity is also a key step in LTM induced by retraining in rodents.…”