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Neuron. 2016 Oct 19;92(2):479-492. doi: 10.1016/j.neuron.2016.09.040.

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

Author information

1
Dominick P. Purpura Department of Neuroscience, Albert Einstein College of Medicine, New York, NY 10461, USA. Electronic address: t.younts@ucl.ac.uk.
2
Dominick P. Purpura Department of Neuroscience, Albert Einstein College of Medicine, New York, NY 10461, USA.
3
Momentum Laboratory of Molecular Neurobiology, Institute of Experimental Medicine, Hungarian Academy of Sciences, Budapest 1051, Hungary; School of Ph.D. Studies, Semmelweis University, Budapest 1085, Hungary.
4
Dominick P. Purpura Department of Neuroscience, Albert Einstein College of Medicine, New York, NY 10461, USA; Department of Psychiatry and Behavioral Sciences, Albert Einstein College of Medicine, New York, NY 10461, USA.
5
Momentum Laboratory of Molecular Neurobiology, Institute of Experimental Medicine, Hungarian Academy of Sciences, Budapest 1051, Hungary.
6
Dominick P. Purpura Department of Neuroscience, Albert Einstein College of Medicine, New York, NY 10461, USA. Electronic address: pablo.castillo@einstein.yu.edu.

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

PMID:
27764673
PMCID:
PMC5119541
DOI:
10.1016/j.neuron.2016.09.040
[Indexed for MEDLINE]
Free PMC Article

Conflict of interest statement

There are no conflicts of interest.

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