Seminar
Abstract:
De novo protein synthesis is required for long-lasting synaptic plasticity and long-term memory consolidation, reconsolidation, and extinction. Numerous studies, including several from our laboratory, have identified signaling cascades, including the mechanistic target of rapamycin complex 1 (mTORC1) signaling pathway, that couple cell surface receptors to the translation regulatory machinery during the formation of long-lasting synaptic plasticity and the consolidation of long-term memory. Downstream effectors of mTORC1 include the eukaryotic initiation factor 4E (eIF4E) and p70 S6 kinase 1 (S6K1). We have shown previously that eIF4E-dependent translation is required for the consolidation of auditory threat memory and for increased polyribosomes in dendritic spine heads, whereas concomitant activation of eIF4E and S6K1 is required for threat memory reconsolidation. We recently have developed inducible and conditional mouse models where translation initiation mediated by either eIF2 or eIF4E can be inhibited in a cell type-specific manner. Using these novel mouse lines, we have identified cell types in the lateral and centrolateral amygdala that require de novo translation for the consolidation of auditory threat memory. Collectively, our findings demonstrate that cell type-specific translation initiation is required for threat memory consolidation.