mTORC1 controls long-term memory retrieval.

Area of Science:

• Neurobiology
• Molecular Neuroscience
• Memory Research

Background:

• Memory retrieval mechanisms, particularly the role of protein synthesis, remain incompletely understood.
• Mammalian target of rapamycin complex 1 (mTORC1), a key protein synthesis regulator, is implicated in synaptic plasticity and memory formation.

Purpose of the Study:

• To investigate the role of mTORC1 in the retrieval of established long-term memories.
• To determine if mTORC1-mediated protein synthesis is required for memory recall across different time scales.

Main Methods:

• Utilized inhibitory avoidance (IA) and object location memory (OLM) tasks in rodents.
• Administered the mTORC1 inhibitor rapamycin and a general protein synthesis inhibitor (emetine) into the dorsal hippocampus and retrosplenial cortex before memory testing.
• Evaluated memory retrieval at various time points post-training (24 hours, 7, 14, and 28 days).

Main Results:

• Rapamycin infusion disrupted long-term memory retrieval when administered shortly before testing (15 or 40 min), but not 3 hours prior, indicating a role in the immediate recall process.
• Emetine produced similar memory impairments, supporting the involvement of protein synthesis.
• mTORC1 inhibition did not affect short-term memory retrieval.
• Rapamycin impaired memory recall at 7 and 14 days post-training but not at 28 days.
• mTORC1 blockade in the retrosplenial cortex also impaired memory retention.

Conclusions:

• Ongoing protein synthesis, dependent on the mTORC1 pathway, is crucial for the retrieval of long-term memories.
• This process appears necessary for memory consolidation and recall at intermediate time points but may be less critical for very long-term memory storage.
• The findings highlight mTORC1 as a potential therapeutic target for modulating memory recall.