A novel crosstalk within the endocannabinoid system controls GABA transmission in the striatum

Abstract The N-palmitoylethanolamine (PEA) is an endogenous member of the endocannabinoid system (ECS) with several biological functions, including a neuromodulatory activity in the central nervous system. To shed light on the neuronal function of PEA, we investigated its involvement in the control...

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Autores principales:	A. Musella, D. Fresegna, F. R. Rizzo, A. Gentile, S. Bullitta, F. De Vito, L. Guadalupi, D. Centonze, G. Mandolesi
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/bf0e3bee978547b3b70d6245162014cb
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spelling	oai:doaj.org-article:bf0e3bee978547b3b70d6245162014cb2021-12-02T16:06:25ZA novel crosstalk within the endocannabinoid system controls GABA transmission in the striatum10.1038/s41598-017-07519-82045-2322https://doaj.org/article/bf0e3bee978547b3b70d6245162014cb2017-08-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-07519-8https://doaj.org/toc/2045-2322Abstract The N-palmitoylethanolamine (PEA) is an endogenous member of the endocannabinoid system (ECS) with several biological functions, including a neuromodulatory activity in the central nervous system. To shed light on the neuronal function of PEA, we investigated its involvement in the control of both excitatory and inhibitory transmission in the murine striatum, a brain region strongly modulated by the ECS. By means of electrophysiological recordings, we showed that PEA modulates inhibitory synaptic transmission, through activation of GPR55 receptors, promoting a transient increase of GABAergic spontaneous inhibitory postsynaptic current (sIPSC) frequency. The subsequently rundown effect on sIPSC frequency was secondary to the delayed stimulation of presynaptic cannabinoid CB1 receptors (CB1Rs) by the endocannabinoid 2-AG, whose synthesis was stimulated by PEA on postsynaptic neurons. Our results indicate that PEA, acting on GPR55, enhances GABA transmission in the striatum, and triggers a parallel synthesis of 2-AG at the postsynaptic site, that in turn acts in a retrograde manner to inhibit GABA release through the stimulation of presynaptic CB1Rs. This electrophysiological study identifies a previously unrecognized function of PEA and of GPR55, demonstrating that GABAergic transmission is under the control of this compound and revealing that PEA modulates the release of the endocannabinoid 2-AG.A. MusellaD. FresegnaF. R. RizzoA. GentileS. BullittaF. De VitoL. GuadalupiD. CentonzeG. MandolesiNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-8 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q A. Musella D. Fresegna F. R. Rizzo A. Gentile S. Bullitta F. De Vito L. Guadalupi D. Centonze G. Mandolesi A novel crosstalk within the endocannabinoid system controls GABA transmission in the striatum
description	Abstract The N-palmitoylethanolamine (PEA) is an endogenous member of the endocannabinoid system (ECS) with several biological functions, including a neuromodulatory activity in the central nervous system. To shed light on the neuronal function of PEA, we investigated its involvement in the control of both excitatory and inhibitory transmission in the murine striatum, a brain region strongly modulated by the ECS. By means of electrophysiological recordings, we showed that PEA modulates inhibitory synaptic transmission, through activation of GPR55 receptors, promoting a transient increase of GABAergic spontaneous inhibitory postsynaptic current (sIPSC) frequency. The subsequently rundown effect on sIPSC frequency was secondary to the delayed stimulation of presynaptic cannabinoid CB1 receptors (CB1Rs) by the endocannabinoid 2-AG, whose synthesis was stimulated by PEA on postsynaptic neurons. Our results indicate that PEA, acting on GPR55, enhances GABA transmission in the striatum, and triggers a parallel synthesis of 2-AG at the postsynaptic site, that in turn acts in a retrograde manner to inhibit GABA release through the stimulation of presynaptic CB1Rs. This electrophysiological study identifies a previously unrecognized function of PEA and of GPR55, demonstrating that GABAergic transmission is under the control of this compound and revealing that PEA modulates the release of the endocannabinoid 2-AG.
format	article
author	A. Musella D. Fresegna F. R. Rizzo A. Gentile S. Bullitta F. De Vito L. Guadalupi D. Centonze G. Mandolesi
author_facet	A. Musella D. Fresegna F. R. Rizzo A. Gentile S. Bullitta F. De Vito L. Guadalupi D. Centonze G. Mandolesi
author_sort	A. Musella
title	A novel crosstalk within the endocannabinoid system controls GABA transmission in the striatum
title_short	A novel crosstalk within the endocannabinoid system controls GABA transmission in the striatum
title_full	A novel crosstalk within the endocannabinoid system controls GABA transmission in the striatum
title_fullStr	A novel crosstalk within the endocannabinoid system controls GABA transmission in the striatum
title_full_unstemmed	A novel crosstalk within the endocannabinoid system controls GABA transmission in the striatum
title_sort	novel crosstalk within the endocannabinoid system controls gaba transmission in the striatum
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/bf0e3bee978547b3b70d6245162014cb
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A novel crosstalk within the endocannabinoid system controls GABA transmission in the striatum

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