Learning and Memory

It has been known for many decades that consolidation of the labile short-term memory to a stable long-term memory requires new protein synthesis. However, the mechanisms coupling the synaptic plasticity-related signalling pathways to the mRNA translation were not clearly known.

Since the early 2000s, our lab has focused on delineating the role of mRNA translation in learning and memory. Seminal works from our lab connecting eIF2α-dependent translational regulation to memory consolidation have been published in Cell, Nature and many other high-impact journals.

We are currently characterizing the cell-type-specific role of several key players in the eIF4E- and eIF2α-pathways in learning and memory. To answer these questions, we use an interdisciplinary approach combing mouse genetics, molecular biology, biochemistry, high-resolution imaging, and behavioural techniques. In addition, the lab is also interested in studying the various neurological disorders related to learning and memory, for example, Alzheimer’s disease, autism spectrum disorder, and Phelan-McDermid syndrome.

Selected Papers:

  1. Argel Aguilar-Valles, Danilo De Gregorio, Edna Matta-Camacho, Mohammad J Eslamizade, Abdessattar Khlaifia, Agnieszka Skaleka, Martha Lopez-Canul, Angelica Torres-Berrio, Sara Bermudez, Gareth M Rurak, Stephanie Simard, Natalina Salmaso, Gabriella Gobbi, Jean-Claude Lacaille, Nahum Sonenberg (2021). Antidepressant actions of ketamine engage cell-specific translation via eIF4E. Nature. doi: 10.1038/s41586-020-03047-0

  2. Vijendra Sharma, Rapita Sood, Abdessattar Khlaifia, Mohammad Javad Eslamizade, Tzu-Yu Hung, Danning Lou, Azam Asgarihafshejani, Maya Lalzar, Stephen J Kiniry, Matthew P Stokes, Noah Cohen, Alissa J Nelson, Kathryn Abell, Anthony P Possemato, Shunit Gal-Ben-Ari, Vinh T Truong, Peng Wang, Adonis Yiannakas, Fatemeh Saffarzadeh, A Claudio Cuello, Karim Nader, Randal J Kaufman, Mauro Costa-Mattioli, Pavel V Baranov, Albert Quintana, Elisenda Sanz, Arkady Khoutorsky, Jean-Claude Lacaille, Kobi Rosenblum, Nahum Sonenberg (2020). eIF2α controls memory consolidation via excitatory and somatostatin neurons. Nature. doi: 10.1038/s41586-020-2805-8

  3. Arkady Khoutorsky, Akiko Yanagiya, Christos G Gkogkas, Marc R Fabian, Masha Prager-Khoutorsky, Ruifeng Cao, Karine Gamache, Frederic Bouthiette, Armen Parsyan, Robert E Sorge, Jeffrey S Mogil, Karim Nader, Jean-Claude Lacaille, Nahum Sonenberg (2013). Control of synaptic plasticity and memory via suppression of poly(A)-binding protein. Neuron. doi: 10.1016/j.neuron.2013.02.025

  4. Mauro Costa-Mattioli, Delphine Gobert, Elad Stern, Karine Gamache, Rodney Colina, Claudio Cuello, Wayne Sossin, Randal Kaufman, Jerry Pelletier, Kobi Rosenblum, Krešimir Krnjević, Jean-Claude Lacaille, Karim Nader, Nahum Sonenberg (2007). eIF2α phosphorylation bidirectionally regulates the switch from short- to long-term synaptic plasticity and memory. Cell. doi: 10.1016/j.cell.2007.01.050

  5. Mauro Costa-Mattioli, Delphine Gobert, Heather Harding, Barbara Herdy, Mounia Azzi, Martin Bruno, Michael Bidinosti, Cyrinne Ben Mamou, Edwige Marcinkiewicz, Madoka Yoshida, Hiroaki Imataka, A Claudio Cuello, Nabil Seidah, Wayne Sossin, Jean-Claude Lacaille, David Ron, Karim Nader, Nahum Sonenberg (2005). Translational control of hippocampal synaptic plasticity and memory by the eIF2alpha kinase GCN2. Nature. doi: 10.1038/nature03897