Differential role of kinases in behavioral-tagging process of aversive memory formation after spaced learning

PABLO BUDRIESI; RAMIRO TINTORELLI; JULIETA CORREA; PAMELA LOPES DA CUNHA; JUAN G. RIBOLDI; DIANA RUEDA ROSERO; HAYDEE VIOLA

Congreso; SAN 2021 XXXVI Annual Meeting; 2021

Sociedad Argentina de Investigacion en Neurociencias

Spaced trainings are more efficient than massed ones to induce long-term memories (LTM). Thus, even weak trainings can achieve LTM if proper spaced protocols are applied. Here we examined the temporal constraints and cellular processes underlying LTM formation by retraining using weak inhibitory-avoidance (wIA) task. A single wIA training is unable to form LTM assessed 24 h later, but two identical wIA sessions spaced by 15 min to 6 h inter-trial intervals, achieve LTM tested at 24 h. This promotion depends on hippocampal protein synthesis and the activity of ERKs, CaMKII and PKA kinases. We analyzed these results under the Behavioral Tagging (BT) hypothesis which postulates that trainings induce “learning tags” in activated neural sites, and there, new synthesized plasticity-related proteins (PRP) are used to form LTMs. We propose that spaced trainings stimulate the same neural populations allowing the additive effect of cellular mechanisms (e.g. ERKs activation) triggered by each session to reach the threshold required for PRP synthesis. Such addition would not occur if neural populations activated by each session differ. Then, combining wIA and spatial-object recognition (wSOR) sessions, did not result in LTM for either task. Our results suggest that LTM promotion via spaced wIA-trainings occurs by BT mechanisms, where ERKs are involved in PRP synthesis but not in tag setting, CaMKII is only involved in tag setting, while PKA is required for both processes to form LTMs.