miR-181a involves in the hippocampus-dependent memory formation via targeting PRKAA1

Post-transcriptional gene regulation by microRNAs ( miRNAs) is involved in memory formation. However, the roles of individual miRNAs in these processes remain largely unknown. In this study, we want to clarify the role of miR-181a in hippocampus-dependent memory formation. A transient increase in miR-181a expression was observed after conditioned fear conditioning (CFC) and object location task (OLT) training. Selective overexpression or inhibition of miR-181a in the dorsal hippocampus (DH) via the injection of a miR-181a agomir or antagomir enhanced or impaired the CFC- and OLT-dependent memory formation, respectively. Using bioinformatics and luciferase assays, we identified PRKAA1 as a potential target gene of miR-181a. After CFC or OLT training, the expression and activity of PRKAA1 decreased as miR-181a expression increased and was effectively blocked by the miR-181a antagomir. Moreover, microinjection of the PRKAA1 agonist AICAR or inhibitor compound C in the DH reversed the roles of the miR-181a agomir or antagomir in CFC- and OLT-dependent memory formation. In conclusion, this work provides novel evidence describing the role and mechanism of miR-181a in hippocampus-dependent memory formation, which sheds light on the potential regulation of cognition and future treatments for cognitive disorders.