Nutritional status-dependent endocannabinoid signalling regulates the integration of rat visceral information.
J Physiol. 2017-03-27; 595(11): 3267-3285
DOI: 10.1113/jp273484
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1. J Physiol. 2017 Jun 1;595(11):3267-3285. doi: 10.1113/JP273484. Epub 2017 Mar 27.
Nutritional status-dependent endocannabinoid signalling regulates the integration
of rat visceral information.
Khlaifia A(1), Matias I(2)(3), Cota D(2)(3), Tell F(1).
Author information:
(1)Aix-Marseille Université, CNRS, CRN2M, UMR 7286, 51 Boulevard Pierre Dramard,
13344, Marseille, France.
(2)INSERM, Neurocentre Magendie, Physiopathologie de la Plasticité Neuronale,
U1215, F-33000, Bordeaux, France.
(3)University of Bordeaux, Neurocentre Magendie, Physiopathologie de la
Plasticité Neuronale, U1215, F-33000, Bordeaux, France.
KEY POINTS: Vagal sensory inputs transmit information from the viscera to
brainstem neurones located in the nucleus tractus solitarii to set physiological
parameters. These excitatory synapses exhibit a CB1 endocannabinoid-induced
long-term depression (LTD) triggered by vagal fibre stimulation. We investigated
the impact of nutritional status on long-term changes in this long-term synaptic
plasticity. Food deprivation prevents LTD induction by disrupting CB1 receptor
signalling. Short-term refeeding restores the capacity of vagal synapses to
express LTD. Ghrelin and cholecystokinin, respectively released during fasting
and refeeding, play a key role in the control of LTD via the activation of energy
sensing pathways such as AMPK and the mTOR and ERK pathways.
ABSTRACT: Communication form the viscera to the brain is essential to set
physiological homoeostatic parameters but also to drive more complex behaviours
such as mood, memory and emotional states. Here we investigated the impact of the
nutritional status on long-term changes in excitatory synaptic transmission in
the nucleus tractus solitarii, a neural hub integrating visceral signals. These
excitatory synapses exhibit a CB1 endocannabinoid (eCB)-induced long-term
depression (LTD) triggered by vagal fibre stimulation. Since eCB signalling is
known to be an important component of homoeostatic regulation of the body and is
regulated during various stressful conditions, we tested the hypothesis that food
deprivation alters eCB signalling in central visceral afferent fibres. Food
deprivation prevents eCB-LTD induction due to the absence of eCB signalling. This
loss was reversed by blockade of ghrelin receptors. Activation of the cellular
fuel sensor AMP-activated protein kinase or inhibition of the mechanistic target
of rapamycin pathway abolished eCB-LTD in free-fed rats. Signals associated with
energy surfeit, such as short-term refeeding, restore eCB-LTD induction, which in
turn requires activation of cholecystokinin receptors and the extracellular
signal-regulated kinase pathway. These data suggest a tight link between eCB-LTD
in the NTS and nutritional status and shed light on the key role of eCB in the
integration of visceral information.
© 2017 Aix Marseille Université. The Journal of Physiology © 2017 The
Physiological Society.
DOI: 10.1113/JP273484
PMCID: PMC5451724
PMID: 28233325 [Indexed for MEDLINE]