mTOR controls hippocampal long-term inhibitory avoidance memory retrieval

PEREYRA M; MEDINA JH; KATCHE C; DE LANDETA, AB

Congreso; XXXII Reunión Anual Sociedad Argentina de Investigación en Neurociencia; 2017

Understanding how stored information emerges is a main question in the neurobiology of memory that is now increasingly gaining attention. Although controversy concerning molecular events required for memory retrieval, protein synthesis has been recently investigated during this memory stage. Mammalian target of rapamycin (mTOR), a central regulator of protein synthesis in neurons, has been implicated in synaptic plasticity and memory. Using inhibitory avoidance(IA), a fear-motivated and hippocampus-dependent task, we evaluate the role of mTOR in memory retrieval. Infusion of a selective mTOR inhibitor, rapamycin, into the dorsal hippocampus 15min and 40min but not 3h before a test session carried out 24h post training impaired memory expression in a reversible way. We observed the same result using emetine, a general protein synthesis inhibitor. Also, the retention impairment caused by rapamycin was observed when testing an already expressed memory. Then, we analyze if the effect seen in long term memory (LTM) depends on the age of the memory studied. mTOR inhibition 15min before test at 7 or 14 days, but not at 2h impaired memory retrieval. As previously reported in our laboratory with pretest hippocampal inactivation induced by muscimol, infusion of rapamycin 15min before test at 28 days did not cause temporal amnesia. Rapamycin infused in retrosplenial cortex, another structure required for IA memory retrieval, also impaired memory retention. Our results support the idea that ongoing protein synthesis mediated by mTOR pathway is necessary for long but not for short term memory when memory still depends on the hippocampus.