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

2016 ◽  
Vol 113 (11) ◽  
pp. 3072-3077 ◽  
Author(s):  
Qian Li ◽  
Xuchen Zhang ◽  
Wantong Hu ◽  
Xitong Liang ◽  
Fang Zhang ◽  
...  

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.

2012 ◽  
Vol 22 (21) ◽  
pp. 1981-1989 ◽  
Author(s):  
Cheng Huang ◽  
Xingguo Zheng ◽  
Hong Zhao ◽  
Min Li ◽  
Pengzhi Wang ◽  
...  

Author(s):  
Wang-Pao Lee ◽  
Meng-Hsuan Chiang ◽  
Li-Yun Chang ◽  
Wei-Huan Shyu ◽  
Tai-Hsiang Chiu ◽  
...  

Memory consolidation is a time-dependent process through which an unstable learned experience is transformed into a stable long-term memory; however, the circuit and molecular mechanisms underlying this process are poorly understood. The Drosophila mushroom body (MB) is a huge brain neuropil that plays a crucial role in olfactory memory. The MB neurons can be generally classified into three subsets: γ, αβ, and α′β′. Here, we report that water-reward long-term memory (wLTM) consolidation requires activity from α′β′-related mushroom body output neurons (MBONs) in a specific time window. wLTM consolidation requires neurotransmission in MBON-γ3β′1 during the 0–2 h period after training, and neurotransmission in MBON-α′2 is required during the 2–4 h period after training. Moreover, neurotransmission in MBON-α′1α′3 is required during the 0–4 h period after training. Intriguingly, blocking neurotransmission during consolidation or inhibiting serotonin biosynthesis in serotoninergic dorsal paired medial (DPM) neurons also disrupted the wLTM, suggesting that wLTM consolidation requires serotonin signals from DPM neurons. The GFP Reconstitution Across Synaptic Partners (GRASP) data showed the connectivity between DPM neurons and MBON-γ3β′1, MBON-α′2, and MBON-α′1α′3, and RNAi-mediated silencing of serotonin receptors in MBON-γ3β′1, MBON-α′2, or MBON-α′1α′3 disrupted wLTM. Taken together, our results suggest that serotonin released from DPM neurons modulates neuronal activity in MBON-γ3β′1, MBON-α′2, and MBON-α′1α′3 at specific time windows, which is critical for the consolidation of wLTM in Drosophila.


2007 ◽  
Vol 88 (3) ◽  
pp. 342-351 ◽  
Author(s):  
Lisa Conboy ◽  
Claire M. Seymour ◽  
Marco P. Monopoli ◽  
Niamh C. O’Sullivan ◽  
Keith J. Murphy ◽  
...  

2017 ◽  
Vol 8 (1) ◽  
Author(s):  
Pierre-Yves Plaçais ◽  
Éloïse de Tredern ◽  
Lisa Scheunemann ◽  
Séverine Trannoy ◽  
Valérie Goguel ◽  
...  

2017 ◽  
Vol 7 (1) ◽  
Author(s):  
Jie-Kai Wu ◽  
Chu-Yi Tai ◽  
Kuan-Lin Feng ◽  
Shiu-Ling Chen ◽  
Chun-Chao Chen ◽  
...  

2019 ◽  
Vol 122 (3) ◽  
pp. 1123-1135 ◽  
Author(s):  
C. J. Scavuzzo ◽  
M. J. LeBlancq ◽  
F. Nargang ◽  
H. Lemieux ◽  
T. J. Hamilton ◽  
...  

The nearly axiomatic idea that de novo protein synthesis is necessary for long-term memory consolidation is based heavily on behavioral studies using translational inhibitors such as anisomycin. Although inhibiting protein synthesis has been shown to disrupt the expression of memory, translational inhibitors also have been found to profoundly disrupt basic neurobiological functions, including the suppression of ongoing neural activity in vivo. In the present study, using transverse hippocampal brain slices, we monitored the passive and active membrane properties of hippocampal CA1 pyramidal neurons using intracellular whole cell recordings during a brief ~30-min exposure to fast-bath-perfused anisomycin. Anisomycin suppressed protein synthesis to 46% of control levels as measured using incorporation of radiolabeled amino acids and autoradiography. During its application, anisomycin caused a significant depolarization of the membrane potential, without any changes in apparent input resistance or membrane time constant. Anisomycin-treated neurons also showed significant decreases in firing frequencies and spike amplitudes, and showed increases in spike width across spike trains, without changes in spike threshold. Because these changes indicated a loss of cellular energetics contributing to maintenance of ionic gradients across the membrane, we confirmed that anisomycin impaired mitochondrial function by reduced staining with 2,3,5-triphenyltetrazolium chloride and also impaired cytochrome c oxidase (complex IV) activity as indicated through high-resolution respirometry. These findings emphasize that anisomycin-induced alterations in neural activity and metabolism are a likely consequence of cell-wide translational inhibition. Critical reevaluation of studies using translational inhibitors to promote the protein synthesis dependent idea of long-term memory is absolutely necessary. NEW & NOTEWORTHY Memory consolidation is thought to be dependent on the synthesis of new proteins because translational inhibitors produce amnesia when administered just after learning. However, these agents also disrupt basic neurobiological functions. We show that blocking protein synthesis disrupts basic membrane properties of hippocampal neurons that correspond to induced disruptions of mitochondrial function. It is likely that translational inhibitors cause amnesia through their disruption of neural activity as a result of dysfunction of intracellular energetics.


Cortex ◽  
2015 ◽  
Vol 63 ◽  
pp. 68-78 ◽  
Author(s):  
Monika Schönauer ◽  
Melanie Grätsch ◽  
Steffen Gais

2015 ◽  
Vol 22 (10) ◽  
pp. 527-531 ◽  
Author(s):  
Jan-Willem Thielen ◽  
Atsuko Takashima ◽  
Femke Rutters ◽  
Indira Tendolkar ◽  
Guillén Fernández

Sign in / Sign up

Export Citation Format

Share Document