Translational control by MAPK signaling in long-term synaptic plasticity and memory

Area of Science:

• Neuroscience
• Molecular Biology
• Cell Signaling

Background:

• Long-lasting memory and synaptic plasticity depend on new protein synthesis.
• The regulatory mechanisms governing this protein synthesis remain largely unknown.
• Mitogen-activated protein kinase (MAPK) signaling pathways are implicated in cellular regulation.

Purpose of the Study:

• To investigate the role of MAPK signaling in regulating protein synthesis for memory.
• To determine the impact of inhibiting MAPK/ERK pathway on hippocampal synaptic plasticity and memory retention.

Main Methods:

• Utilized conditional expression of a dominant-negative MEK1 mutant in the murine forebrain.
• Assessed effects on ERK activation, hippocampal long-term potentiation (LTP), and memory retention.
• Examined neuronal activity-induced protein synthesis and translation factor phosphorylation in hippocampal neurons and slices.

Main Results:

• Inhibition of MEK1/ERK signaling selectively impaired hippocampal memory retention and a specific phase of LTP.
• ERK inhibition blocked activity-induced translation and phosphorylation of key translation factors (eIF4E, 4EBP1, S6).
• Protein synthesis and translation factor phosphorylation during LTP and memory formation were significantly reduced in mutant mice.

Conclusions:

• MAPK signaling, specifically via ERK, plays a critical role in translational control.
• This translational control is essential for enduring forms of synaptic plasticity and memory.
• The findings highlight MAPK signaling as a key regulator of memory consolidation processes.