Pre- and postsynaptic N-methyl-D-aspartate receptors are required for sequential printing of fear memory engrams

• Published in: iScience 2023-11, Vol.26 (11), p.108050-108050, Article 108050
• Main Authors: Bertocchi, Ilaria, Rocha-Almeida, Florbela, Romero-Barragán, María Teresa, Cambiaghi, Marco, Carretero-Guillén, Alejandro, Botta, Paolo, Dogbevia, Godwin K., Treviño, Mario, Mele, Paolo, Oberto, Alessandra, Larkum, Matthew E., Gruart, Agnes, Sprengel, Rolf, Delgado-García, José Maria, Hasan, Mazahir T.
• Format: Article
• Language: English
• Subjects: Behavioral neuroscience; Cellular neuroscience
• ISSN: 2589-0042; 2589-0042
• DOI: 10.1016/j.isci.2023.108050

The organization of fear memory involves the participation of multiple brain regions. However, it is largely unknown how fear memory is formed, which circuit pathways are used for “printing” memory engrams across brain regions, and the role of identified brain circuits in memory retrieval. With advanced genetic methods, we combinatorially blocked presynaptic output and manipulated N-methyl-D-aspartate receptor (NMDAR) in the basolateral amygdala (BLA) and medial prefrontal cortex (mPFC) before and after cued fear conditioning. Further, we tagged fear-activated neurons during associative learning for optogenetic memory recall. We found that presynaptic mPFC and postsynaptic BLA NMDARs are required for fear memory formation, but not expression. Our results provide strong evidence that NMDAR-dependent synaptic plasticity drives multi-trace systems consolidation for the sequential printing of fear memory engrams from BLA to mPFC and, subsequently, to the other regions, for flexible memory retrieval. [Display omitted] •We selectively manipulated NMDARs, synaptic transmission, and engram tagging•Cued memory is sequentially printed first from BLA to mPFC, then to other regions•mPFC pre- and BLA postsynaptic NMDARs are required for cued memory formation•Memory can be flexibly retrieved from BLA or mPFC neurons Behavioral neuroscience; Cellular neuroscience