Translational control of imprinting and structural plasticity during an early critical period in chickens

Summary

Date: 
February 1, 2017 - 11:30am
Location: 
Northwest 425
About the Speaker
Name: 
Gervasio Batista
Speaker Affiliation: 
Albert Einstein College of Medicine

Memory consolidation requires protein synthesis. While the molecular machinery regulating experience-dependent protein synthesis in adulthood has been extensively studied, the mechanisms underlying memory consolidation during early critical periods remain unknown. We addressed this question studying imprinting, a specific form of learning occurring within the first days after hatching, in newborn chickens. Since translation initiation is a rate-limiting step in protein synthesis, we focused on the role of the translation initiation factor eIF2α and the kinase complex mTORC1 during the critical period. Using SUnSET, a method to visualize newly synthesized proteins in vivo, we found that imprinting to arbitrary sounds and virtual objects leads to increase in protein synthesis in specific forebrain regions, involved in imprinting, the mediorostral nidopallium/mesopallium (MNM) and the intermediate medial mesopallium (IMM). We assessed experience-dependent activation of eIF2α and mTORC1 in imprinting relevant areas using western blots. eIF2α was activated exclusively in MNM (auditory area) while mTORC1 was activated both in IMM (visual area) and MNM. Following this finding, a series of gain- and loss-of-function experiments demonstrated that the signaling pathways underlying imprinting in the auditory and sensory modalities were not identical. While visual imprinting only required mTORC1, auditory imprinting required dephosphorylation of the translation initiation factor eIF2α in addition to activation of the kinase complex mTORC1. To further understand how eIF2α and mTORC1 regulate imprinting we investigated experience-dependent structural plasticity. We found that training during the critical period triggers an increase in mushroom-type spines. Using pharmacology we showed that eIF2α dephosphorylation was required specifically for structural plasticity in the auditory pathway, while mTORC1 mediated spine remodeling in both auditory and visual nuclei. Subsequently, we asked whether targeting upstream molecules to enhance eIF2α and mTORC1 signaling, outside of the critical period, could restore behavioral plasticity selectively in each modality. Indeed, facilitating eIF2α-mediated translation restored auditory imprinting and mTORC1 activation restored imprinting across sensory modalities.. Thus we found two molecular mechanisms important for the formation of early imprinted memories and related structural plasticity. Moreover, we demonstrated that targeting eIF2α and mTORC1 pathways can rejuvenate plasticity once the critical period is closed.