Schedule of Events | Symposia

Neuron-specific oligomerization of prion-like protein Orb2 required for long-term memory

Poster Session B - Sunday, March 30, 2025, 8:00 – 10:00 am EDT, Back Bay Ballroom/Republic Ballroom

Weijia LI¹ (wlidh@connect.ust.hk), Yukinori HIRANO¹; ¹Hong Kong University of Science and Technology

The synapse tag hypothesis predicted the persistent memory substrate at the activated synapses, linking synaptic plasticity to behavioral memory. Orb2, a prion-like RNA-binding protein in Drosophila, is a potential candidate for the synapse tag, required for long-term memory (LTM), which represses translation in a monomeric state and converts to an oligomeric state inducing translation by neural activity. Although Orb2 oligomerization and the local translation could sustain the plastic change of synapses, the dynamic nature of Orb2 in vivo has not been explored. Here, we report that Orb2 oligomerization could occur locally within or near limited neurons in Drosophila. We conducted aversive olfactory memory assays and employed optogenetic techniques to simultaneously activate dopamine and mushroom body (MB) neurons, mimicking learning. Notably, co-expression of CsChrimson in these neurons robustly induced punctate Orb2 localization preferentially within and near one of the MB subpopulations, the MB α/β core neurons. Paradoxically, olfactory aversive LTM was not affected by Orb2-knockdown in MB α/β core neurons but was impaired by that in MB α/β surface and γ main neurons, indicating that Orb2 expressed in MB α/β surface neurons, and potentially MB γ main neurons as well, translocate and form oligomers near MB α/β core neurons, which is significant for memory consolidation. Thus, translocation of the prion-like protein Orb2 may modify the neural circuit's local design through oligomerization to operate for memory consolidation.

Topic Area: LONG-TERM MEMORY: Other