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. Author manuscript; available in PMC: 2022 Oct 20.
Published in final edited form as: Neuron. 2021 Aug 26;109(20):3211–3227. doi: 10.1016/j.neuron.2021.08.001

Figure 5: Memory Suppressors that Act on Forgetting.

Figure 5:

Memory suppressor genes are in bold and color-coded green (fly), blue (mouse), and purple (both mouse and fly). A) Caspase-2 activity initiates a multi-step signaling cascade, starting with the cleavage of Rictor in the protein complex mTORC2. This results in the activation of the kinase AKT followed by the kinase GSK3β. Activated dendritic GSK3β phosphorylates the AMPAR subunit GluA2, inducing AMPAR internalization and a weakening of synaptic strength. Syt3 also regulates AMPAR internalization through GluA2, driving clathrin-mediated endocytosis of AMPARs.

B) Dopamine-driven active forgetting in Drosophila is mediated by the Gαq-coupled DAMB receptor. DAMB signals downstream to a protein complex that includes Rac1. Rac accelerates forgetting in both mice and Drosophila. In Drosophila, Rac1 propagates the forgetting signal to cofilin that induces actin filament severing and to dia that promotes actin filament elongation. CDC42 drives forgetting of consolidated memory through ARP2/3, a protein that controls the branching of actin filaments. Upstream activators involved in CDC42-facilitated forgetting are not known.