Fatty-acid–binding protein 5 controls retrograde endocannabinoid signaling at central glutamate synapses

Endocannabinoids (eCBs) are lipid-signaling molecules involved in the regulation of numerous behaviors and physiological functions. Released by postsynaptic neurons, eCBs mediate retrograde modulation of synaptic transmission and plasticity by activating presynaptic cannabinoid receptors. While the...

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Bibliographic Details
Published in:Proceedings of the National Academy of Sciences - PNAS 2018-03, Vol.115 (13), p.3482-3487
Main Authors: Haj-Dahmane, Samir, Shen, Roh-Yu, Elmes, Matthew W., Studholme, Keith, Kanjiya, Martha P., Bogdan, Diane, Thanos, Panayotis K., Miyauchi, Jeremy T., Tsirka, Stella E., Deutsch, Dale G., Kaczocha, Martin
Format: Article
Language:English
Subjects:
Acids
Animals
Arachidonic Acids - metabolism
Biological Sciences
Cannabinoid receptors
Cells, Cultured
Clonal deletion
Cognition & reasoning
Dorsal raphe nucleus
Endocannabinoids - metabolism
Endocannabinoids - pharmacology
Fatty Acid-Binding Proteins - physiology
Fatty acids
Glutamic Acid - metabolism
Glycerides - metabolism
Glycerol
Inhibition
Lipids
Male
Marijuana
Mice
Mice, Inbred C57BL
Mice, Knockout
Neoplasm Proteins - physiology
Pharmacology
Plastic foam
Presynaptic plasticity
Proteins
Raphe nuclei
Rats
Rats, Sprague-Dawley
Receptor mechanisms
Receptor, Cannabinoid, CB1 - metabolism
Receptors
Signaling
Synapses
Synapses - drug effects
Synapses - physiology
Synaptic plasticity
Synaptic transmission
Synaptic Transmission - drug effects
Transport
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Summary:Endocannabinoids (eCBs) are lipid-signaling molecules involved in the regulation of numerous behaviors and physiological functions. Released by postsynaptic neurons, eCBs mediate retrograde modulation of synaptic transmission and plasticity by activating presynaptic cannabinoid receptors. While the cellular mechanisms by which eCBs control synaptic function have been well characterized, the mechanisms controlling their retrograde synaptic transport remain unknown. Here, we demonstrate that fatty-acid–binding protein 5 (FABP5), a canonical intracellular carrier of eCBs, is indispensable for retrograde eCB transport in the dorsal raphe nucleus (DRn). Thus, pharmacological inhibition or genetic deletion of FABP5 abolishes both phasic and tonic eCB-mediated control of excitatory synaptic transmission in the DRn. The blockade of retrograde eCB signaling induced by FABP5 inhibition is not mediated by impaired cannabinoid receptor function or reduced eCB synthesis. These findings indicate that FABP5 is essential for retrograde eCB signaling and may serve as a synaptic carrier of eCBs at central synapses.
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.1721339115