Physiopathology of Endocannabioid System
Our laboratory is interested in studying the endocannabionoid system in physio-pathological conditions at brain level. Currently, we are mainly focused on the role of cannabinoid (CB1 and CB2) and vanilloid (TRPV1) receptors in the emotional-affective, cognitive and sensory aspects of chronic pain. Moreover, the interplay of endocannabinoid signalling with another system highly involved in nociception, ie. the NGF one, is also object of investigation. Notably, chronic pain conditions cause depression and anxiety and vice versa patients with depression and/or anxiety feel pain intensely. To this regard, specific brain areas, such as the cingulate and somatosensory cortex, undergo changes following persistent activation of the nociceptive circuits and the synaptic strength increased due to a synaptic excitatory facilitation or reduction in inhibition.
Using a combination of behavioral, electrophysiological, pharmacological and immunohistological techniques we aim at identifying alterations of excitatory and inhibitory circuits at both glial and neuronal level with a focus on changes of endocannabinoid signaling components in control and after an injury, such as the chronic constriction ligature of the sciatic nerve.
Among ongoing projects in the lab, the cellular mechanism of drug self-administration in relation to the setting of drug intake is also assessed. To address this point, we use behavioral pharmacology (intravenous drug self administration) and ex vivo electrophysiology on the cortical-accumbens synapses.
Fig. confocal image
Pyramidal neurons of Anterior cingulate cortex stained with the SMI-32 primary antibody
Fig. infrared image and firing , respectively
Infrared image of a pyramidal neuron and its electrical activity
After obtaining her Master’s Degree in Pharmacology at the University of Roma “La Sapienza” in 1996, Silvia Marinelli continued her graduate student training with Prof. P. Calabresi at the University of Rome “Tor Vergata” (1997-1998) and subsequently did her PhD in the laboratory of Prof. N.B. Mercuri at the Fondazione Santa Lucia in Rome.
From 1999 to 2001 she worked in the Department of Pharmacology – University of Sydney (Australia) in the laboratory of Prof. Mac D. Christie. In 2002 she returned to the laboratory of Prof. Mercuri to continue her Postdoctoral research.
From 2006-2010 she worked as Senior Scientist in the laboratory of Alberto Bacci at the European Brain Research Institute (EBRI) in Rome.
Her research studies have focused mainly a) on the role of vanilloid receptor type 1 in different brain areas, b) functional and anatomical characterization of serotoninergic neurons involved in the descending nocicpation pathway and c) and the endocannabinoid involvement in a form of self-inhibition of neocortical principal and GABAergic neurons.
In 2011 she was appointed Junior Group Leader of the laboratory Endocannabinoid and Neuropathic Pain at the EBRI. She is recipient of a young investigator grant by the Italian Ministry of Health.
- Manseau F, Marinelli S, Schwaller B, Mendez P, Prince DA, Huguenard JR, Bacci A. Desynchronization of neocortical networks by asynchronous release of GABA at autaptic and synaptic contacts from fast-spiking interneurons. Plos Biology Vol 8 (9) 2010.
- Marinelli S, Pacioni S, Cannich A, Marsicano G, Bacci A. (2009).Self-modulation of neocortical glutamatergic neurons by endocannabinoids. Nature Neurosci12:1488-90.
- Marinelli S, Pacioni S, Bisogno T, Di Marzo V, Prince DA, Huguenard JR, Bacci A. (2008). The endocannabinoid 2-AG is responsible for the slow self-inhibition in neocortical interneurons. J Neurosci 28:13532-13541.
- Marinelli S, Di Marzo V, Florenzano F, ViscomiMT, FezzaF, van der SteltM, Bernardi G, Molinari M, Maccarroneand Mercuri NB. N-arachidonoyldopamine tunes synaptic transmission onto dopaminergic neurones by activating both cannabinoid and vanilloid receptors. Neurospychopharmacology (2007)32, 298-308.
- Marinelli S, Connor M, Schnell SA, Christie MJ, Wessendorf MW, Vaughan CW. Delta-opioid receptor-mediated actions on rostral ventromedial medulla neurons. Neuroscience2005;132(2):239-44.
- Marinelli S., T. Pascucci, G. Bernardi, S. Puglisi-Allegra, and N. B. Mercuri. Activation of TRPV1 in the VTA excites dopaminergic neurons and increases chemical- and noxious-induced dopamine release in the nucleus accumbens. Neuropsychopharmacology (2005)May;30(5):864-70.
- Marinelli S, Schnell SA, Hack SP, Christie MJ, Wessendorf MW and Vaughan CW. Serotonergic and nonserotonergic dorsal raphe neurons are pharmacologically and electrophysiologically heterogeneous. J Neurophysiol. 2004 Dec; 92(6):3532-7.
- Marinelli S, Di Marzo V,BerrettaN, MatiasI, Maccarrone M, Bernardi G and MercuriNB: Presynaptic facilitation of glutamatergic synapses to dopaminergic neurons of the rat substantia nigra by endogenous stimulation of vanilloid receptors. J. Neuroscience 23(8):3136-3144 (2003)
- Marinelli S, Schnell S, Vaughan CW, Wessendorf MW, Christie MJ: Rostral ventromedial medulla neurons that project to the spinal cord express multiple opioid receptor phenotypes. J. Neuroscience, 22(24): 10847-10855 (2002).
- Marinelli S, Vaughan CW, Christie MJ, Connor M: Capsaicin activationof glutamatergic synaptic transmission in the rat locus coeruleus in vitro. J. Physiology 543, pp. 531-540, 2002.
- Vaughan CW, Connor M, Jennings EA, Marinelli S, Allen RG, Christie MJ: Actions of nociceptin/orphanin FQ and other prepronociceptin products on rat rostral ventromedial medulla neurons in vitro. J. Physiology 543(3), pp.849-859, 2001
- Marinelli S, FedericiM, Bernardi G, Mercuri NB: Hypoglycaemia enhances ionotropic but reduced metabotropic glutamate current in rat substantia nigra dopaminergic neurons. J Neurophysiology 85, pp.1159-1166, 2001
- Marinelli S, Bernardi G, Giacomini P, Mercuri NB: Pharmacological identification of the K+ currents mediating the hypoglycaemic hyperpolarisation of rat midbrain dopaminergic neurons. Neuropharmacology, vol 39 (6), pp. 1021-1028, 2000.
- Marinelli S, Gatta F, Sagratella S: Effect of GYKI 52466 and some 2,3-benzodiazepinederivates on hippocampal in vitro basal neuronal excitability and 4-aminopiridine epileptic activity. Eur. J. Pharmacol, 391(1-2), pp75-80, 2000
- Sagratella S and Marinelli S: Effect on some GABA and NMDA antagonists on a model of presynaptic hippocampal paired pulse inhibition: Prog. Neuropsycopharmacol. Biol. Psychiatry: vol 24 (2), pp. 327-336, 2000