RRC ID 49643
Author Hylin MJ, Zhao J, Tangavelou K, Rozas NS, Hood KN, MacGowan JS, Moore AN, Dash PK.
Title A role for autophagy in long-term spatial memory formation in male rodents.
Journal J Neurosci Res
Abstract 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.
Volume 96(3)
Pages 416-426
Published 2018-3-1
DOI 10.1002/jnr.24121
PMID 29230855
PMC PMC6425965
MeSH Adenine / analogs & derivatives* Adenine / pharmacology Animals Antigens, Nuclear / metabolism Autophagy / drug effects* Autophagy / physiology* Beclin-1 / metabolism Benzylamines / pharmacology* Glial Fibrillary Acidic Protein / metabolism Hippocampus / cytology Hippocampus / drug effects Hippocampus / metabolism Male Maze Learning / drug effects Maze Learning / physiology Memory, Long-Term / drug effects* Memory, Long-Term / physiology* Memory, Short-Term / drug effects Memory, Short-Term / physiology Mice Microtubule-Associated Proteins / metabolism Nerve Tissue Proteins / metabolism Phosphatidylinositol 3-Kinase / metabolism Phosphorylation Quinazolines / pharmacology* Rats Rats, Long-Evans Spatial Memory / drug effects Spatial Memory / physiology
IF 4.699
Times Cited 13
Mice RBRC00806