@article{6bf14c1046384eb7b8f3365ed06fbcb5,
title = "Presynaptic FMRP and local protein synthesis support structural and functional plasticity of glutamatergic axon terminals",
abstract = "Learning and memory rely on long-lasting, synapse-specific modifications. Although postsynaptic forms of plasticity typically require local protein synthesis, whether and how local protein synthesis contributes to presynaptic changes remain unclear. Here, we examined the mouse hippocampal mossy fiber (MF)-CA3 synapse, which expresses both structural and functional presynaptic plasticity and contains presynaptic fragile X messenger ribonucleoprotein (FMRP), an RNA-binding protein involved in postsynaptic protein-synthesis-dependent plasticity. We report that MF boutons contain ribosomes and synthesize protein locally. The long-term potentiation of MF-CA3 synaptic transmission (MF-LTP) was associated with the translation-dependent enlargement of MF boutons. Remarkably, increasing in vitro or in vivo MF activity enhanced the protein synthesis in MFs. Moreover, the deletion of presynaptic FMRP blocked structural and functional MF-LTP, suggesting that FMRP is a critical regulator of presynaptic MF plasticity. Thus, presynaptic FMRP and protein synthesis dynamically control presynaptic structure and function in the mature mammalian brain.",
keywords = "LTP, RNA-binding protein, enriched environment, fragile X syndrome, hippocampus, protein synthesis, structural plasticity",
author = "Monday, {Hannah R.} and Kharod, {Shivani C.} and Yoon, {Young J.} and Singer, {Robert H.} and Castillo, {Pablo E.}",
note = "Funding Information: We thank all Castillo Lab and Singer Lab members and Dr. Benjamin Hobson for helpful discussions. We thank Dr. Kostantin Dobrenis, Kevin Fisher, and Vladimir Mudragel of the Einstein Neural Cell Engineering and Imaging Core (supported by the Rose F. Kennedy Intellectual Disabilities Research Center) for their advice and assistance with image acquisition and analysis. We thank Dr. Stefano Lutzu for whole-cell recordings (Figure S6C). We are grateful to Dr. Mary Kay Lobo University of Maryland, Baltimore County, for donating the Ribotag mice; Drs. Ga{\"e}l Barthet and Christophe Mulle, Universit{\'e} de Bordeaux, for sharing the C1ql2 constructs; the FRAXA foundation for the Fmr1fl/fl mouse line; and the Lavis Lab for the JF dyes. This research was supported by the National Institutes of Health: F31MH114431 to H.R.M.; R01-MH125772, R01-NS113600, R01-NS115543, R01-MH116673, and a pilot grant through NICHD U54 HD090260 to P.E.C.; R01-NS083085 to R.H.S.; R21-MH120496 to Y.J.Y.; R01-NS083085 to R.H.S.; and a shared instrument grant (S10OD025295) to Konstantin Dobrenis. Conceptualization, H.R.M. P.E.C. S.C.K. Y.J.Y. and R.H.S.; methodology, H.R.M. and Y.J.Y.; investigation, H.R.M. and S.C.K.; resources, Y.J.Y. R.H.S. and P.E.C.; writing – original draft, H.R.M. and P.E.C.; writing – review & editing, all authors; visualization, H.R.M. and S.C.K.; supervision, H.R.M. and P.E.C.; funding acquisition, H.R.M. Y.J.Y. R.H.S. and P.E.C.; project administration, P.E.C. The authors declare no competing interests. Funding Information: We thank all Castillo Lab and Singer Lab members and Dr. Benjamin Hobson for helpful discussions. We thank Dr. Kostantin Dobrenis, Kevin Fisher, and Vladimir Mudragel of the Einstein Neural Cell Engineering and Imaging Core (supported by the Rose F. Kennedy Intellectual Disabilities Research Center ) for their advice and assistance with image acquisition and analysis. We thank Dr. Stefano Lutzu for whole-cell recordings ( Figure S6 C). We are grateful to Dr. Mary Kay Lobo University of Maryland, Baltimore County, for donating the Ribotag mice; Drs. Ga{\"e}l Barthet and Christophe Mulle, Universit{\'e} de Bordeaux, for sharing the C1ql2 constructs; the FRAXA foundation for the Fmr1 fl/fl mouse line; and the Lavis Lab for the JF dyes. This research was supported by the National Institutes of Health : F31MH114431 to H.R.M.; R01-MH125772 , R01-NS113600 , R01-NS115543 , R01-MH116673 , and a pilot grant through NICHD U54 HD090260 to P.E.C.; R01-NS083085 to R.H.S.; R21-MH120496 to Y.J.Y.; R01-NS083085 to R.H.S.; and a shared instrument grant ( S10OD025295 ) to Konstantin Dobrenis. Publisher Copyright: {\textcopyright} 2022 Elsevier Inc.",
year = "2022",
month = aug,
day = "17",
doi = "10.1016/j.neuron.2022.05.024",
language = "English (US)",
volume = "110",
pages = "2588--2606.e6",
journal = "Neuron",
issn = "0896-6273",
publisher = "Cell Press",
number = "16",
}