A hallmark of long-term memory formation is the requirement for protein synthesis. Administration of protein synthesis inhibitors impairs long-term memory formation without influencing short-term memory. Rapamycin is a specific inhibitor of target of rapamycin complex 1 (TORC1) that has been shown to block protein synthesis and impair long-term memory. In addition to regulating protein synthesis, TORC1 also phosphorylates Unc-51-like autophagy activating kinase-1 (Ulk-1) to suppress autophagy. As autophagy can be activated by rapamycin (and rapamycin inhibits long-term memory), our aim was to test the hypothesis that autophagy inhibitors would enhance long-term memory. To examine if learning alters autophagosome number, we used male reporter mice carrying the GFP-LC3 transgene. Using these mice, we observed that training in the Morris water maze task increases the number of autophagosomes, a finding contrary to our expectations. For learning and memory studies, male Long Evans rats were used due to their relatively larger size (compared to mice), making it easier to perform intrahippocampal infusions in awake, moving animals. When the autophagy inhibitors 3-methyladenine (3-MA) or Spautin-1 were administered bilaterally into the hippocampii prior to training in the Morris water maze task, the drugs did not alter learning. In contrast, when memory was tested 24 hours later by a probe trial, significant impairments were observed. In addition, intrahippocampal infusion of an autophagy activator peptide (TAT-Beclin-1) improved long-term memory. These results indicate that autophagy is not necessary for learning, but is required for long-term memory formation.
Pubmed ID: 29230855 RIS Download
Publication data is provided by the National Library of Medicine ® and PubMed ®. Data is retrieved from PubMed ® on a weekly schedule. For terms and conditions see the National Library of Medicine Terms and Conditions.
This monoclonal targets β-Actin
View all literature mentionsThis monoclonal targets Atg16L1
View all literature mentionsThis polyclonal targets Beclin-1
View all literature mentionsThis monoclonal targets GFP
View all literature mentionsThis monoclonal targets PI3 Kinase Class III (D4E2) Rabbit mAb
View all literature mentionsThis monoclonal targets LC3B (D11) XP Rabbit mAb
View all literature mentionsThis unknown targets IgG (H+L)
View all literature mentionsThis polyclonal targets Glial Fibrillary Acidic Protein (GFAP)
View all literature mentionsThis monoclonal targets MAP2 clone 5F9
View all literature mentionsThis unknown targets
View all literature mentionsThis polyclonal secondary targets Rabbit IgG (H+L)
View all literature mentionsMus musculus with name B6.Cg-Tg(CAG-GFP/LC3)53Nmz/NmzRbrc from IMSR.
View all literature mentionsOpen source Java based image processing software program designed for scientific multidimensional images. ImageJ has been transformed to ImageJ2 application to improve data engine to be sufficient to analyze modern datasets.
View all literature mentionsVideo tracking software that tracks and analyzes the behavior, movement, and activity of any animal.
View all literature mentionsThis monoclonal targets β-Actin
View all literature mentionsThis monoclonal targets PI3 Kinase Class III (D4E2) Rabbit mAb
View all literature mentionsThis polyclonal targets Beclin-1
View all literature mentionsThis monoclonal targets LC3B (D11) XP Rabbit mAb
View all literature mentionsThis polyclonal targets Beclin-1
View all literature mentionsThis monoclonal targets LC3B (D11) XP Rabbit mAb
View all literature mentionsThis monoclonal targets GFP
View all literature mentionsThis monoclonal targets Atg16L1
View all literature mentionsThis monoclonal targets GFP
View all literature mentionsThis monoclonal targets Atg16L1
View all literature mentionsThis monoclonal targets β-Actin
View all literature mentionsThis monoclonal targets PI3 Kinase Class III (D4E2) Rabbit mAb
View all literature mentions