Memory Retrieval at the Crossroads of mTORC1 Pathway and AMPA Receptors

DALTO, JULIANA F; PEREYRA, MAGDALENA; KATCHE, CYNTHIA; DE LANDETA, ANA BELÉN; MEDINA, JORGE H.

Congreso; XXXIII Congress of the Argentine Society for Research in Neuroscience; 2018

Recently we found that mTORC1 activity close in time to memory retrieval is required for normal expression of aversive and nonaversive long-term memories. Here we used inhibitory-avoidance task to evaluate the potential mechanisms by which mTORC1 signaling pathway participates in memory retrieval. As mTORC1 is necessary during consolidation to increase levels of GluA1-containing AMPA receptors (AMPAR) at the synapse, we assessed if a similar mechanism accounts for memory retrieval. Intrahippocampal infusion of GluA1 antisense but not GluA1 missense oligonucleotides 3 hr before testing impaired memory retention. The same result was observed upon delivery of GluA2 antisense oligonucleotides 3 hr before test, thus showing the necessity of GluA1 and GluA2 AMPAR subunits for memory retrieval. We next studied the role of GluA-subunit trafficking during memory recall and its relationship with mTORC1 pathway. We performed intrahippocampal infusion of GluA23Ç, a peptide that selectively interferes with the endocytosis of GluA2-containing AMPAR, 30 min before rapamycin infusion, which inhibits mTORC1 signaling pathway. We found that GluA23Ç prevented memory impairment caused by mTORC1 inactivation. Our work indicates that de novo GluA1 and GluA2 AMPAR subunits are required for memory retrieval and suggests that mTORC1 regulates AMPAR trafficking during retrieval.