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Depolarization-induced release of endocannabinoids by murine dorsal motor nucleus of the vagus nerve neurons differentially regulates inhibitory and excitatory neurotransmission.
Neuropharmacology. 2009 Jun; 56(8):1106-15.N

Abstract

Numerous studies, focused on the hypothalamus, have recently implicated endocannabinoids (EC) as orexigenic factors in the central control of food intake. However, the EC system is also highly expressed in the hindbrain autonomic integrator of food intake regulation, i.e. the dorsal vagal complex (DVC). Previous studies have shown that exogenous cannabinoids, by acting on cannabinoid 1 receptor (CB1R), suppress GABAergic and glutamatergic neuronal transmission in adult rat dorsal motor nucleus of the vagus nerve (DMNV), the principal efferent compartment of the DVC. However, no endogenous release of EC has been demonstrated in DVC to date. Using patch-clamp techniques on mouse coronal brainstem slices, we confirmed that both inhibitory and excitatory neurotransmission were depressed by WIN 55,212-2, a CB1R agonist. We demonstrated that DMNV neurons exhibited a rapid and reversible depolarization-induced suppression of electrically evoked GABAergic IPSCs (eIPSCs), classically known as DSI (depolarization-induced suppression of inhibition), while spontaneous or miniature IPSCs activity remained unaltered. Further, no depolarization-induced suppression of glutamatergic eEPSCs (DSE) occurred. Our results indicate that DSI was blocked by SR141716A (Rimonabant), a selective CB1R antagonist, and was dependent on calcium elevation in DMNV neurons, suggesting a release of EC in the DVC. Moreover, the analysis of the paired-pulse ratio, of the coefficient of variation and of the failure rate of eIPSCs support the fact that EC-mediated suppression of GABAergic inhibition takes place at the presynaptic level. These results show for the first time that DMNV neurons release EC in an activity-dependent manner, which in turn differentially regulates their inhibitory and excitatory synaptic inputs.

Authors+Show Affiliations

Centre de Recherche en Neurobiologie-Neurophysiologie de Marseille, Université Paul Cézanne, Université de la Méditerranée, CNRS UMR, USC-INRA, Département de Physiologie Neurovégétative, Faculté des Sciences et Techniques St Jérôme, Marseille, France.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

19332082

Citation

Roux, Julien, et al. "Depolarization-induced Release of Endocannabinoids By Murine Dorsal Motor Nucleus of the Vagus Nerve Neurons Differentially Regulates Inhibitory and Excitatory Neurotransmission." Neuropharmacology, vol. 56, no. 8, 2009, pp. 1106-15.
Roux J, Wanaverbecq N, Jean A, et al. Depolarization-induced release of endocannabinoids by murine dorsal motor nucleus of the vagus nerve neurons differentially regulates inhibitory and excitatory neurotransmission. Neuropharmacology. 2009;56(8):1106-15.
Roux, J., Wanaverbecq, N., Jean, A., Lebrun, B., & Trouslard, J. (2009). Depolarization-induced release of endocannabinoids by murine dorsal motor nucleus of the vagus nerve neurons differentially regulates inhibitory and excitatory neurotransmission. Neuropharmacology, 56(8), 1106-15. https://doi.org/10.1016/j.neuropharm.2009.03.009
Roux J, et al. Depolarization-induced Release of Endocannabinoids By Murine Dorsal Motor Nucleus of the Vagus Nerve Neurons Differentially Regulates Inhibitory and Excitatory Neurotransmission. Neuropharmacology. 2009;56(8):1106-15. PubMed PMID: 19332082.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Depolarization-induced release of endocannabinoids by murine dorsal motor nucleus of the vagus nerve neurons differentially regulates inhibitory and excitatory neurotransmission. AU - Roux,Julien, AU - Wanaverbecq,Nicolas, AU - Jean,André, AU - Lebrun,Bruno, AU - Trouslard,Jérôme, Y1 - 2009/03/28/ PY - 2008/10/07/received PY - 2009/02/26/revised PY - 2009/03/18/accepted PY - 2009/4/1/entrez PY - 2009/4/1/pubmed PY - 2009/8/29/medline SP - 1106 EP - 15 JF - Neuropharmacology JO - Neuropharmacology VL - 56 IS - 8 N2 - Numerous studies, focused on the hypothalamus, have recently implicated endocannabinoids (EC) as orexigenic factors in the central control of food intake. However, the EC system is also highly expressed in the hindbrain autonomic integrator of food intake regulation, i.e. the dorsal vagal complex (DVC). Previous studies have shown that exogenous cannabinoids, by acting on cannabinoid 1 receptor (CB1R), suppress GABAergic and glutamatergic neuronal transmission in adult rat dorsal motor nucleus of the vagus nerve (DMNV), the principal efferent compartment of the DVC. However, no endogenous release of EC has been demonstrated in DVC to date. Using patch-clamp techniques on mouse coronal brainstem slices, we confirmed that both inhibitory and excitatory neurotransmission were depressed by WIN 55,212-2, a CB1R agonist. We demonstrated that DMNV neurons exhibited a rapid and reversible depolarization-induced suppression of electrically evoked GABAergic IPSCs (eIPSCs), classically known as DSI (depolarization-induced suppression of inhibition), while spontaneous or miniature IPSCs activity remained unaltered. Further, no depolarization-induced suppression of glutamatergic eEPSCs (DSE) occurred. Our results indicate that DSI was blocked by SR141716A (Rimonabant), a selective CB1R antagonist, and was dependent on calcium elevation in DMNV neurons, suggesting a release of EC in the DVC. Moreover, the analysis of the paired-pulse ratio, of the coefficient of variation and of the failure rate of eIPSCs support the fact that EC-mediated suppression of GABAergic inhibition takes place at the presynaptic level. These results show for the first time that DMNV neurons release EC in an activity-dependent manner, which in turn differentially regulates their inhibitory and excitatory synaptic inputs. SN - 1873-7064 UR - https://www.unboundmedicine.com/medline/citation/19332082/Depolarization_induced_release_of_endocannabinoids_by_murine_dorsal_motor_nucleus_of_the_vagus_nerve_neurons_differentially_regulates_inhibitory_and_excitatory_neurotransmission_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0028-3908(09)00086-0 DB - PRIME DP - Unbound Medicine ER -