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001-es BibID:	BIBFORM062728
Első szerző:	Kovács Adrienn (molekuláris biológus)
Cím:	Direct presynaptic and indirect astrocyte-mediated mechanisms both contribute to endocannabinoid signaling in the pedunculopontine nucleus of mice / Kovács A., Bordás Cs., Bíró T., Hegyi Z., Antal M., Szücs P., Pál B.
Dátum:	2017
ISSN:	1863-2653 1863-2661
Megjegyzések:	The pedunculopontine nucleus (PPN), a cholinergic nucleus of the reticular activating system, is known to be involved in the regulation of sleep and wakefulness. Endogenous and exogenous cannabinoids, either by systemic or local administration to the pedunculopontine nucleus can both influence sleep. We previously demonstrated that activation of astrocytes by cannabinoid type 1 (CB1) receptor agonists was able to modulate the membrane potential of PPN neurons, even in the presence of blockers of fast synaptic neurotransmission. In the present work we provide evidence that synaptic inputs of PPN neurons are also affected by activation of presynaptic and astrocytic CB1 receptors.Using slice electrophysiology combined with calcium imaging, optogenetics and immunohistochemistry, we revealed a direct presynaptic inhibitory action on inhibitory postsynaptic currents, along with a mild increase of excitatory postsynaptic currents during CB1 receptor stimulation. Besides inhibition of excitatory and inhibitory neurotransmission through stimulation of presynaptic CB1 receptors, astrocyte- and mGluR-dependent tonic inhibition and excitation also developed. The mild stimulatory action of CB1 receptor activation on excitatory neurotransmission is the combination of astrocyte-dependent tonic excitation on excitatory neurons and the canonical presynaptic CB1 receptor activation and consequential inhibition of excitatory synaptic neurotransmission, whereas the astrocyte-dependent stimulatory action was not observed on inhibitory neurotransmission within the PPN.Our findings demonstrate that endocannabinoids act in the PPN via a dual pathway, consisting of a direct presynaptic and an indirect, astrocyte-mediated component, regulating synaptic strength and neuronal activity via independent mechanisms.
Tárgyszavak:	Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban pedunculopontine nucleus CB1 receptor optogenetics astrocyte neuromodulation
Megjelenés:	Brain Structure & Function 222 : 1 (2017), p. 247-266. -
További szerzők:	Bordás Csilla Bíró Tamás (1968-) (élettanász) Hegyi Zoltán (1983-) (molekuláris biológus) Antal Miklós (1951-) (orvos, anatómus) Szűcs Péter (1974-) (kutatóorvos) Pál Balázs (1975-) (élettanász)
Pályázati támogatás:	Nemzeti Agykutatási Program KTIA_13_NAP-A-I/10 Egyéb Nemzeti Agykutatási Program KTIA_NAP_13-1-2013-0001 Egyéb Nemzeti Agykutatási Program KTIA_NAP_13-2-2014-0005 Egyéb MTA-TKI 242 MTA TÁMOP-4.2.2.B-15/1/KONV-2015-0001 TÁMOP
Internet cím:	Intézményi repozitóriumban (DEA) tárolt változat DOI
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