@article{8fbcc2165ec04b43a73a5c9c1fe4a2b0,
title = "Presynaptic Protein Synthesis Is Required for Long-Term Plasticity of GABA Release",
abstract = "Long-term changes of neurotransmitter release are critical for proper brain function. However, the molecular mechanisms underlying these changes are poorly understood. While protein synthesis is crucial for the consolidation of postsynaptic plasticity, whether and how protein synthesis regulates presynaptic plasticity in the mature mammalian brain remain unclear. Here, using paired whole-cell recordings in rodent hippocampal slices, we report that presynaptic protein synthesis is required for long-term, but not short-term, plasticity of GABA release from type 1 cannabinoid receptor (CB1)-expressing axons. This long-term depression of inhibitory transmission (iLTD) involves cap-dependent protein synthesis in presynaptic interneuron axons, but not somata. Translation is required during the induction, but not maintenance, of iLTD. Mechanistically, CB1 activation enhances protein synthesis via the mTOR pathway. Furthermore, using super-resolution STORM microscopy, we revealed eukaryotic ribosomes in CB1-expressing axon terminals. These findings suggest that presynaptic local protein synthesis controls neurotransmitter release during long-term plasticity in the mature mammalian brain.",
keywords = "CB1 receptor, GABA, LTD, endocannabinoid, inhibition, interneuron, presynaptic, protein translation, superresolution microscopy, synaptic plasticity",
author = "Younts, {Thomas J.} and Monday, {Hannah R.} and Barna Dudok and Klein, {Matthew E.} and Jordan, {Bryen A.} and Istv{\'a}n Katona and Castillo, {Pablo E.}",
note = "Funding Information: We thank all P.E.C. lab members for discussions; Stefano Lutzu and Pablo Lituma for technical assistance with field recordings and two-photon laser imaging and Carlton Christie for field recordings; Bal{\'a}zs Pint{\'e}r and Erika Tischler for technical assistance; and Kata Kenesei, M{\'a}t{\'e} Kisfali, and Benjamin Barti for slices. We acknowledge Vera DesMarais and David Entenberg at the Einstein Analytical Imaging Facility for help with second harmonic generation microscopy and L{\'a}szl{\'o} Barna, the Nikon Microscopy Center at the Institute of Experimental Medicine, Nikon Europe B.V., Nikon Austria GmbH, and Auro-Science Consulting Kft for providing STORM microscopy support. We also thank Masahiko Watanabe for antibodies. This work was supported by the NIH ( R01-MH081935 and R01-DA17392 to P.E.C., R01-NIAAG039521 to B.A.J., and F31-NS073200 and T32-GM007288 to M.E.K.), the European Research Council (grant 243153 ), the Momentum Program ( LP2013-54/2013 ), a Wellcome Trust International Senior Research Fellowship ( 090946/Z/09/Z to I.K.), and, in later stages, The Royal Society (Newton International Fellowship to T.J.Y.). Publisher Copyright: {\textcopyright} 2016 Elsevier Inc.",
year = "2016",
month = oct,
day = "19",
doi = "10.1016/j.neuron.2016.09.040",
language = "English (US)",
volume = "92",
pages = "479--492",
journal = "Neuron",
issn = "0896-6273",
publisher = "Cell Press",
number = "2",
}