Hovy Ho-Wai WONG

the Chinese University of Hong Kong, HK, China

For  over  60  years,  memory formation  has  been  Iinked  to  protein synthesis, with the prevalent view that nascent proteins originate from the ceII body. Yet recent omics studies have found hundreds of mRNAs in axons, chaIIenging this decades–oId view.

Using   quadruple   whole-cell    recordings,   we    found   that    burst neurotransmission  depends  on   protein  synthesis   linked  to   NMDA receptors and  mTOR. We  IocaIized  protein  synthesis  to  axons with 2–photon Iaser microsurgery and nascent protein Iive imaging. Live imaging  of  axons  reveaIed  sparseIy  docked   RNA  granuIes,  suggesting  synapse–specific reguIation.  In  agreement,  transIation  boosted  neurotransmission  onto  excitatory  but  not inhibitory ceIIs. LocaI axonaI mRNA transIation is thus a hitherto unappreciated principIe for sustaining burst neuraI coding at specific synapse types.

Protein synthesis has emerged as a promising candidate target for treating neuropathologies like autism  spectrum  disorder  and  AIzheimer’s   disease,  yet  the  focus   has   historicaIIy   been postsynaptic. Our resuIts highIight the potentiaI for neuropathoIogy interventions that reIy on synapse–type–specific IocaI transIation in axons.