Faculty

Stefano Vicini Professor of Physiology Ph.D., Biophysics University of Torino, Italy 1979 (202) 687-6441 svicin01@georgetown.edu

My laboratory is studying excitatory (glutamate) and inhibitory (GABA) amino acid - mediated synapses by electrophysiological (Patch-clamp recordings), anatomical (immunocytochemistry) and pharmacological techniques. The structural determinants of these synapses are responsible for the proper developmental pattern of connections throughout the CNS through synapse formation and modification and therefore they are involved in the control of plasticity in the CNS. Alterations of these receptor systems have been implicated in the pathogenesis of major neurological and psychiatric disorders. On the basis of results on specific and remarkable differences of functional properties at selected CNS synapses that I gathered in the past years, I am investigating the postsynaptic receptor molecular assemblies as structural determinants of synaptic strength.

My general hypothesis is that the postsynaptic receptors for amino acid neurotransmitter themselves are the most important determinants of the synaptic strength. Alterations of these receptors may underlie the primary cause of neurodegenerative disorders. Therefore, I am resolving the specific properties of postsynaptic amino acid receptors in neurons of rat visual cortex and cerebellum performing single-channel current recordings (patch-clamp) in brain slices and primary neuronal cultures. I am also comparing native with recombinant NMDA and GABAa receptors for their functional and pharmacological characteristics. I am also using subunit specific antibodies to study the subcellular localization of distinct receptor subtypes in neurons.

Selected Publications:

• Lee KJ, Queenan BN, Rozeboom AM, Bellmore R, Lim ST, Vicini S, Pak DT. Mossy fiber-CA3 synapses mediate homeostatic plasticity in mature hippocampal neurons. Neuron. 77:99-114, 2013

• Panuccio G, Vicini S, Avoli M. Cell type-specific properties of subicular GABAergic currents shape hippocampal output firing mode. PLoS One. 7:e50241, 2012

• Luo R, Janssen MJ, Partridge JG, Vicini S. Direct and GABA-mediated indirect effects of nicotinic ACh receptor agonists on striatal neurones. J Physiol. 591:203-217, 2013

• Gonzalez-Sulser A, Wang J, Queenan BN, Avoli M, Vicini S, Dzakpasu R. Hippocampal neuron firing and local field potentials in the in vitro 4-aminopyridine epilepsy model. J Neurophysiol. 108:2568-80, 2012

• Menghetti E, Musacchio P, Tawill L, Vicini S, Spagnolo A. [Obesity and arterial hypertension in children: current calamity]. Clin Ter. 163:e107-110, 2012

• Forcelli PA, Janssen MJ, Vicini S, Gale K. Neonatal exposure to antiepileptic drugs disrupts striatal synaptic development. Ann Neurol. 72:363-72, 2012

• Herman MA, Gillis RA, Vicini S, Dretchen KL, Sahibzada N. Tonic GABAA receptor conductance in medial subnucleus of the tractus solitarius neurons is inhibited by activation of mu-opioid receptors. J Neurophysiol. 107(3):1022-31. 2012

• Motamedi GK, Gonzalez-Sulser A, Dzakpasu R, Vicini S. Cellular Mechanisms of Desynchronizing Effects of Hypothermia in an In Vitro Epilepsy Model. Neurotherapeutics.

• Janssen MJ, Yasuda RP, Vicini S. GABA(A) Receptor {beta}3 Subunit Expression Regulates Tonic Current in Developing Striatopallidal Medium Spiny Neurons. Front Cell Neurosci. 5:15, 2011

• Vicini S. The FGIN period: electrophysiological studies. Pharmacol Res. 64(4):316-8, 20

• Chiou TT, Bonhomme B, Jin H, Miralles CP, Xiao H, Fu Z, Harvey RJ, Harvey K, Vicini S, De Blas AL. Differential regulation of the postsynaptic clustering of {gamma}-aminobutyric acid type A (GABAA) receptors by collybistin isoforms. J Biol Chem. 286(25):22456-68, 2011

• Lecanu L, Hashim AI, McCourty A, Giscos-Douriez I, Dinca I, Yao W, Vicini S, Szabo G, Erdelyi F, Greeson J, Papadopoulos V. The naturally occurring steroid solasodine induces neurogenesis in vitro and in vivo. Neurosciencee. 183:251-64, 2011

• Manso M, Carvalho ML, Queralt I, Vicini S, Princi E. Investigation of the composition of historical and modern Italian papers by energy dispersive X-ray fluorescence (EDXRF), X-ray diffraction (XRD), and scanning electron microscopy energy dispersive spectrometry (SEM-EDS). Appl Spectrosc. 65(1):52-9, 2011

• Gonzalez-Sulser A, Wang J, Motamedi GK, Avoli M, Vicini S, Dzakpasu R. The 4-aminopyridine in vitro epilepsy model analyzed with a perforated multi-electrode array. Neuropharmacology. 60(7-8):1142-53, 2011

• Princi E, Vicini S, Stagnaro P, Conzatti L. The nanostructured morphology of linear polyurethanes observed by transmission electron microscopy. Micron. 42(1):3-7, 2011 [Epub ahead of print]

• Kaminski RM, Fu Z, Venkatesan K, Mazzuferi M, Leclercq K, Seutin V, Vicini S. 11-Deoxycortisol impedes GABAergic neurotransmission and induces drug-resistant status epilepticus in mice. Neuropharmacology. 60(7-8):1098-108, 2011

• Adedoyin MO, Vicini S, Neale JH. Endogenous N-acetylaspartylglutamate (NAAG) inhibits synaptic plasticity/transmission in the amygdala in a mouse inflammatory pain model. Mol Pain. 6:60, 2010

• Lin H, Vicini S, Hsu FC, Doshi S, Takano H, Coulter DA, Lynch DR. Axonal {alpha}7 nicotinic ACh receptors modulate presynaptic NMDA receptor expression and structural plasticity of glutamatergic presynaptic boutons. Proc Natl Acad Sci USA. 107(38):16661-6, 2010

• Swanwick CC, Shapiro ME, Vicini S, Wenthold RJ. Flotillin-1 promotes formation of glutamatergic synapses in hippocampal neurons. Dev Neurobiol. 70(13):875-83, 2010

• Forcelli PA, Janssen MJ, Stamps LA, Sweeney C, Vicini S, Gale K. Therapeutic strategies to avoid long-term adverse outcomes of neonatal antiepileptic drug exposure. Epilepsia. 51:18-23, 2010

• Swanwick CC, Shapiro ME, Vicini S, Wenthold RJ. Flotillin-1 mediates neurite branching induced by synaptic adhesion-like molecule 4 in hippocampal neurons. Mol Cell Neurosci. 45(3):213-25, 20100

• Feng LR, Federoff HJ, Vicini S, Maguire-Zeiss KA. Alpha-synuclein mediates alterations in membrane conductance: a potential role for alpha-synuclein oligomers in cell vulnerability. Eur J Neurosci. 32(1):10-7, 2010

• Young JP, Beckerman J, Vicini S, Myers A. Acetylsalicylic acid enhances purinergic receptor-mediated outward currents in rat megakaryocytes. Am J Physiol Cell Physiol. 298(3):C602-10, 2010

• Bennis H, Benslimane R, Vicini S, Mairani A, Princi E. Fibre width measurement and quantification of filler size distribution in paper-based materials by SEM and image analysis. J Electron Microsc (Tokyo). 59(2):91-102, 2010

• Hoy JL, Constable JR, Vicini S, Fu Z, Washbourne P. SynCAM1 recruits NMDA receptors via protein 4.1B. Mol Cell Neurosci. 42(4):466-83, 2009

• Partridge JG, Janssen sen MJ, Chou DY, Abe K, Zukowska Z, Vicini S. Excitatory and inhibitory synapses in neuropeptide Y-expressing striatal interneurons. J Neurophysiol. 102:3038-45, 2009

• Fu Z, Vicini S.: Neuroligin-2 accelerates GABAergic synapse maturation in cerebellar granule cells. Mol Cell Neurosci. 2009

• Janssen MJ, Ade KK, Fu Z, Vicini S.: Dopamine modulation of GABA tonic conductance in striatal output neurons. J Neurosci. 22;29:5116-26, 2009

• Hoe HS, Fu Z, Makarova A, Lee JY, Lu C, Feng L, Pajoohesh-Ganji A, Matsuoka Y, Hyman BT, Ehlers MD, Vicini S, Pak DT, Rebeck GW.: The effects of amyloid precursor protein on postsynaptic composition and activity. J Biol Chem. 284:8495-506, 2009

• Vicini S.: The role of GABA and glutamate on adult neurogenesis. J Physiol.15;586:3737-8, 2008

• Castro K, Proietti N, Princi E, Pessanha S, Carvalho ML, Vicini S, Capitani D, Madariaga JM.: Analysis of a coloured Dutch map from the eighteenth century: the need for a multi-analytical spectroscopic approach using portable instrumentation. Anal Chim Acta. 15;623:187-94, 2008

• Toscano CD, Ueda Y, Tomita YA, Vicini S, Bosetti F.: Altered GABAergic neurotransmission is associated with increased kainate-induced seizure in prostaglandin-endoperoxide synthase-2 deficient mice. Brain Res Bull. 75:598-609, 2008

• Ade KK, Janssen MJ, Ortinski PI, Vicini S.: Differential tonic GABA conductances in striatal medium spiny neurons. J Neurosci. 30;28:1185-97, 2008

• Yi Z, Petralia RS, Fu Z, Swanwick CC, Wang YX, Prybylowski K, Sans N, Vicini S, Wenthold RJ.: The role of the PDZ protein GIPC in regulating NMDA receptor trafficking. J Neurosci. 27:11663-75, Oct 2007

• Ait Kbir M, Benslimane R, Princi E, Vicini S, Pedemonte E.: Filler segmentation of SEM paper images based on mathematical morphology. Ann Chim. 97:575-82, 2007

• Logan SM, Partridge JG, Matta JA, Buonanno A, Vicini S.: Long-lasting NMDA receptor-mediated EPSCs in mouse striatal medium spiny neurons. J Neurophysiol. 98:2693-704, 2007

• Mozrzymas JW, Barberis A, Vicini S.: GABAergic currents in RT and VB thalamic nuclei follow kinetic pattern of alpha3- and alpha1-subunit-containing GABAA receptors. Eur J Neurosci. 26:657-65, 2007

• Barberis A, Mozrzymas JW, Ortinski PI, Vicini S.: Desensitization and binding properties determine distinct alpha1beta2gamma2 and alpha3beta2gamma2 GABA(A) receptor-channel kinetic behavior. Eur J Neurosci. 25:2726-40, 2007

• Fiszman ML, Erdélyi F, Szabó G, Vicini S.: Presynaptic AMPA and kainate receptors increase the size of GABAergic terminals and enhance GABA release. Neuropharmacology. 52:1631-40, 2007

• Kim BG, Dai HN, McAtee M, Vicini S, Bregman BS.: Labeling of dendritic spines with the carbocyanine dye DiI for confocal microscopic imaging in lightly fixed cortical slices. J Neurosci Methods. 162:237-43, 2007

• Lytle JM, Vicini S, Wrathall JR.: Phenotypic changes in NG2+ cells after spinal cord injury. J Neurotrauma. 23:1726-38, 2006

• Proietti N, Capitani D, Cozzolino S, Valentini M, Pedemonte E, Princi E, Vicini S, Segre AL.: In situ and frontal polymerization for the consolidation of porous stones: a unilateral NMR and magnetic resonance imaging study. J Phys Chem B. 110:23719-28, 2006

• Ortinski PI, Turner JR, Barberis A, Motamedi G, Yasuda RP, Wolfe BB, Kellar KJ, Vicini S.: Deletion of the GABA(A) receptor alpha1 subunit increases tonic GABA(A) receptor current: a role for GABA uptake transporters. J Neurosci. 26:9323-31, 2006

• Lu C, Fu Z, Karavanov I, Yasuda RP, Wolfe BB, Buonanno A, Vicini S.: NMDA receptor subtypes at autaptic synapses of cerebellar granule neurons. J Neurophysiol. 96:2282-94, 2006

• Motamedi GK, Salazar P, Smith EL, Lesser RP, Webber WR, Ortinski PI, Vicini S, Rogawski MA.: Termination of epileptiform activity by cooling in rat hippocampal slice epilepsy models. Epilepsy Res. 70:200-10, 2006

• Hoe HS, Magill LA, Guenette S, Fu Z, Vicini S, Rebeck GW.: FE65 interaction with the ApoE receptor ApoEr2. J Biol Chem. 281:24521-30, 2006

• Kim BG, Dai HN, McAtee M, Vicini S, Bregman BS.: Remodeling of synaptic structures in the motor cortex following spinal cord injury. Exp Neurol. 198:401-15, 2006

• Kaminski RM, Marini H, Ortinski PI, Vicini S, Rogawski MA.: The pheromone androstenol (5 alpha-androst-16-en-3 alpha-ol) is a neurosteroid positive modulator of GABAA receptors. J Pharmacol Exp Ther. 317:694-703, 2006

• Hoe HS, Pocivavsek A, Chakraborty G, Fu Z, Vicini S, Ehlers MD, Rebeck GW.: Apolipoprotein E receptor 2 interactions with the N-methyl-D-aspartate receptor. J Biol Chem. 281:3425-31, 2006

• Vicini S.: GABA comes first to newly generated neurons. Focus on "GABAergic signal to newborn neurons in dentate gyrus". J Neurophysiol. 94:3661, 2005

• Prybylowski K, Chang K, Sans N, Kan L, Vicini S, Wenthold RJ.: The synaptic localization of NR2B-containing NMDA receptors is controlled by interactions with PDZ proteins and AP-2. Neuron. 47:845-57, 2005

• Fiszman ML, Barberis A, Lu C, Fu Z, Erdélyi F, Szabó G, Vicini S.: NMDA receptors increase the size of GABAergic terminals and enhance GABA release. J Neurosci. 25:2024-31, 2005

• Fu Z, Logan SM, Vicini S.: Deletion of the NR2A subunit prevents developmental changes of NMDA-mEPSCs in cultured mouse cerebellar granule neurones. J Physiol. 563:867-81, 2005

• Cappitelli F, Vicini S, Piaggio P, Abbruscato P, Princi E, Casadevall A, Nosanchuk JD, Zanardini E.: Investigation of fungal deterioration of synthetic paint binders using vibrational spectroscopic techniques. Macromol Biosci. 5:49-57, 2005

• Barberis A, Lu C, Vicini S, Mozrzymas JW.: Developmental changes of GABA synaptic transient in cerebellar granule cells. Mol Pharmacol. 67:1221-8, 2005

• Vicini S.: A cerebellar synapse for "heavy duty" transmission. Biophys J. 88:1505-6, 2005

• Vicini S, Ortinski P.: Genetic manipulations of GABAA receptor in mice make inhibition exciting. Pharmacol Ther. 103:109-20, 2004

• Hernandez SC, Vicini S, Xiao Y, Dávila-García MI, Yasuda RP, Wolfe BB, Kellar KJ.: The nicotinic receptor in the rat pineal gland is an alpha3beta4 subtype. Mol Pharmacol. 66:978-87, 2004

• Olszewski RT, Bukhari N, Zhou J, Kozikowski AP, Wroblewski JT, Shamimi-Noori S, Wroblewska B, Bzdega T, Vicini S, Barton FB, Neale JH.: NAAG peptidase inhibition reduces locomotor activity and some stereotypes in the PCP model of schizophrenia via group II mGluR. J Neurochem. 89:876-85, 2004

• Ortinski PI, Lu C, Takagaki K, Fu Z, Vicini S.: Expression of distinct alpha subunits of GABAA receptor regulates inhibitory synaptic strength. J Neurophysiol. 92:1718-27, 2004

• De Murtas M, Tatarelli R, Girardi P, Vicini S.: Repeated electroconvulsive stimulation impairs long-term depression in the neostriatum. Biol Psychiatry. 55:472-6, 2004

• Losi G, Vicini S, Neale J.: NAAG fails to antagonize synaptic and extrasynaptic NMDA receptors in cerebellar granule neurons. Neuropharmacology. 46:490-6, 2004

• Fu Z, Washbourne P, Ortinski P, Vicini S.: Functional excitatory synapses in HEK293 cells expressing neuroligin and glutamate receptors. J Neurophysiol. 90:3950-7, 2003

• Sans N, Prybylowski K, Petralia RS, Chang K, Wang YX, Racca C, Vicini S, Wenthold RJ.: NMDA receptor trafficking through an interaction between PDZ proteins and the exocyst complex. Nat Cell Biol. 5:520-30, 2003

• Borodinsky LN, O'Leary D, Neale JH, Vicini S, Coso OA, Fiszman ML.: GABA-induced neurite outgrowth of cerebellar granule cells is mediated by GABA(A) receptor activation, calcium influx and CaMKII and erk1/2 pathways. J Neurochem. 84:1411-20, 2003

• Losi G, Prybylowski K, Fu Z, Luo J, Wenthold RJ, Vicini S.: PSD-95 regulates NMDA receptors in developing cerebellar granule neurons of the rat. J Physiol. 548:21-9, 2003

• Ramadan E, Fu Z, Losi G, Homanics GE, Neale JH, Vicini S.: GABA(A) receptor beta3 subunit deletion decreases alpha2/3 subunits and IPSC duration. J Neurophysiol. 89:128-34, 2003

• Sahibzada N, Ferreira M Jr, Williams B, Wasserman A, Vicini S, Gillis RA.: Nicotinic ACh receptor subtypes on gastrointestinally projecting neurones in the dorsal motor vagal nucleus of the rat. J Physiol. 545:1007-16, 2002

• Ha BK, Vicini S, Rogers RC, Bresnahan JC, Burry RW, Beattie MS.: Kainate-induced excitotoxicity is dependent upon extracellular potassium concentrations that regulate the activity of AMPA/KA type glutamate receptors. J Neurochem. 83:934-45, 2002

• Al-Hallaq RA, Jarabek BR, Fu Z, Vicini S, Wolfe BB, Yasuda RP.: Association of NR3A with the N-methyl-D-aspartate receptor NR1 and NR2 subunits. Mol Pharmacol. 62:1119-27, 2002

• Prybylowski K, Fu Z, Losi G, Hawkins LM, Luo J, Chang K, Wenthold RJ, Vicini S.: Relationship between availability of NMDA receptor subunits and their expression at the synapse. J Neurosci. 22:8902-10, 2002

• Vicini S, Losi G, Homanics GE.: GABA(A) receptor delta subunit deletion prevents neurosteroid modulation of inhibitory synaptic currents in cerebellar neurons. Neuropharmacology. 43:646-50, 2002

• Lea PM, Custer SJ, Vicini S, Faden AI.: Neuronal and glial mGluR5 modulation prevents stretch-induced enhancement of NMDA receptor current. Pharmacol Biochem Behav. 73:287-98, 2002

• Losi G, Prybylowski K, Fu Z, Luo JH, Vicini S.: Silent synapses in developing cerebellar granule neurons. J Neurophysiol. 87:1263-70, 2002

• Vicini S, Ferguson C, Prybylowski K, Kralic J, Morrow AL, Homanics GE.: GABA(A) receptor alpha1 subunit deletion prevents developmental changes of inhibitory synaptic currents in cerebellar neurons. J Neurosci. 21:3009-16, 2001