Presynaptic Protein Synthesis Is Required for Long-Term Plasticity of GABA Release

Thomas J. Younts, Hannah R. Monday, Barna Dudok, Matthew E. Klein, Bryen A. Jordan, I. Katona, Pablo E. Castillo

Research output: Contribution to journalArticle

55 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)479-492
Number of pages14
JournalNeuron
Volume92
Issue number2
DOIs
Publication statusPublished - Oct 19 2016

Fingerprint

gamma-Aminobutyric Acid
Proteins
Neurotransmitter Agents
Axons
Brain
Cannabinoid Receptor CB1
Presynaptic Terminals
Carisoprodol
Patch-Clamp Techniques
Interneurons
Ribosomes
Microscopy
Rodentia
Maintenance

Keywords

  • CB1 receptor
  • endocannabinoid
  • GABA
  • inhibition
  • interneuron
  • LTD
  • presynaptic
  • protein translation
  • superresolution microscopy
  • synaptic plasticity

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Younts, T. J., Monday, H. R., Dudok, B., Klein, M. E., Jordan, B. A., Katona, I., & Castillo, P. E. (2016). Presynaptic Protein Synthesis Is Required for Long-Term Plasticity of GABA Release. Neuron, 92(2), 479-492. https://doi.org/10.1016/j.neuron.2016.09.040

Presynaptic Protein Synthesis Is Required for Long-Term Plasticity of GABA Release. / Younts, Thomas J.; Monday, Hannah R.; Dudok, Barna; Klein, Matthew E.; Jordan, Bryen A.; Katona, I.; Castillo, Pablo E.

In: Neuron, Vol. 92, No. 2, 19.10.2016, p. 479-492.

Research output: Contribution to journalArticle

Younts, TJ, Monday, HR, Dudok, B, Klein, ME, Jordan, BA, Katona, I & Castillo, PE 2016, 'Presynaptic Protein Synthesis Is Required for Long-Term Plasticity of GABA Release', Neuron, vol. 92, no. 2, pp. 479-492. https://doi.org/10.1016/j.neuron.2016.09.040
Younts, Thomas J. ; Monday, Hannah R. ; Dudok, Barna ; Klein, Matthew E. ; Jordan, Bryen A. ; Katona, I. ; Castillo, Pablo E. / Presynaptic Protein Synthesis Is Required for Long-Term Plasticity of GABA Release. In: Neuron. 2016 ; Vol. 92, No. 2. pp. 479-492.
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