P Greengard

The Rockefeller University, New York City, New York, United States

Are you P Greengard?

Claim your profile

Publications (830)7256.54 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: Recurrent axon collaterals are a major means of communication between spiny projection neurons (SPNs) in the striatum and profoundly affect the function of the basal ganglia. However, little is known about the molecular and cellular mechanisms that underlie this communication. We show that intrastriatal nitric oxide (NO) signaling elevates the expression of the vesicular GABA transporter (VGAT) within recurrent collaterals of SPNs. Down-regulation of striatal NO signaling resulted in an attenuation of GABAergic signaling in SPN local collaterals, down-regulation of VGAT expression in local processes of SPNs, and impaired motor behavior. PKG1 and cAMP response element-binding protein are involved in the signal transduction that transcriptionally regulates VGAT by NO. These data suggest that transcriptional control of the vesicular GABA transporter by NO regulates GABA transmission and action selection.
    Proceedings of the National Academy of Sciences 11/2014; · 9.81 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Background The high rate of comorbidity between depression and cocaine addiction suggests shared molecular mechanisms and anatomical pathways. Limbic structures, such as the Nucleus Accumbens (NAc), play a crucial role in both disorders, yet how different cell types within these structures contribute to the pathogenesis remains elusive. Downregulation of p11 (S100A10) specifically in the NAc elicits depressive-like behaviors in mice but its role in drug addiction is unknown. Methods We combine mouse genetics and viral strategies to determine how the titration of p11 levels within the entire NAc affects the rewarding actions of cocaine on behavior (6 to 8 mice per group) and molecular correlates (3 experiments, 5 to 8 mice per group). Finally, the manipulation of p11 expression in distinct NAc dopaminoceptive neuronal subsets distinguished cell-type specific effects of p11 on cocaine reward (5 to 8 mice per group) Results We demonstrate that p11 knockout mice have enhanced cocaine conditioned place preference (CPP), which is reproduced by the focal downregulation of p11 in the NAc of wild-type mice. In wild-type mice, cocaine reduced p11 expression in the NAc, while p11 overexpression exclusively in the NAc reduced cocaine CPP. Finally, we identify dopamine receptor-1 (D1) expressing medium spiny neurons (MSNs) as key mediators of p11’s effects on cocaine reward. Conclusions Our data provide evidence that disruption of p11 homeostasis in the NAc particularly in D1-expressing MSNs may underlie pathophysiological mechanisms of cocaine rewarding action. Treatments to counter maladaptation of p11 levels may provide novel therapeutic opportunities for cocaine addiction.
    Biological psychiatry 11/2014; · 8.93 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: The striatum is widely viewed as the fulcrum of pathophysiology in Parkinson's disease (PD) and L-DOPA-induced dyskinesia (LID). In these disease states, the balance in activity of striatal direct pathway spiny projection neurons (dSPNs) and indirect pathway spiny projection neurons (iSPNs) is disrupted, leading to aberrant action selection. However, it is unclear whether countervailing mechanisms are engaged in these states. Here we report that iSPN intrinsic excitability and excitatory corticostriatal synaptic connectivity were lower in PD models than normal; L-DOPA treatment restored these properties. Conversely, dSPN intrinsic excitability was elevated in tissue from PD models and suppressed in LID models. Although the synaptic connectivity of dSPNs did not change in PD models, it fell with L-DOPA treatment. In neither case, however, was the strength of corticostriatal connections globally scaled. Thus, SPNs manifested homeostatic adaptations in intrinsic excitability and in the number but not strength of excitatory corticostriatal synapses
    Nature Communications 10/2014; 5(5316). · 10.74 Impact Factor
  • Source
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: STEP (STriatal-Enriched protein tyrosine Phosphatase) is a neuron-specific phosphatase that regulates N-methyl-D-aspartate receptor (NMDAR) and α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) trafficking, as well as ERK1/2, p38, Fyn, and Pyk2 activity. STEP is overactive in several neuropsychiatric and neurodegenerative disorders, including Alzheimer's disease (AD). The increase in STEP activity likely disrupts synaptic function and contributes to the cognitive deficits in AD. AD mice lacking STEP have restored levels of glutamate receptors on synaptosomal membranes and improved cognitive function, results that suggest STEP as a novel therapeutic target for AD. Here we describe the first large-scale effort to identify and characterize small-molecule STEP inhibitors. We identified the benzopentathiepin 8-(trifluoromethyl)-1,2,3,4,5-benzopentathiepin-6-amine hydrochloride (known as TC-2153) as an inhibitor of STEP with an IC50 of 24.6 nM. TC-2153 represents a novel class of PTP inhibitors based upon a cyclic polysulfide pharmacophore that forms a reversible covalent bond with the catalytic cysteine in STEP. In cell-based secondary assays, TC-2153 increased tyrosine phosphorylation of STEP substrates ERK1/2, Pyk2, and GluN2B, and exhibited no toxicity in cortical cultures. Validation and specificity experiments performed in wild-type (WT) and STEP knockout (KO) cortical cells and in vivo in WT and STEP KO mice suggest specificity of inhibitors towards STEP compared to highly homologous tyrosine phosphatases. Furthermore, TC-2153 improved cognitive function in several cognitive tasks in 6- and 12-mo-old triple transgenic AD (3xTg-AD) mice, with no change in beta amyloid and phospho-tau levels.
    PLoS biology. 08/2014; 12(8):e1001923.
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Huntington's disease (HD) is an autosomal dominant neurodegenerative disorder. The debilitating choreic movements that plague HD patients have been attributed to striatal degeneration induced by the loss of cortically supplied brain-derived neurotrophic factor (BDNF). Here, we show that in mouse models of early symptomatic HD, BDNF delivery to the striatum and its activation of tyrosine-related kinase B (TrkB) receptors were normal. However, in striatal neurons responsible for movement suppression, TrkB receptors failed to properly engage postsynaptic signaling mechanisms controlling the induction of potentiation at corticostriatal synapses. Plasticity was rescued by inhibiting p75 neurotrophin receptor (p75NTR) signaling or its downstream target phosphatase-and-tensin-homolog-deleted-on-chromosome-10 (PTEN). Thus, corticostriatal synaptic dysfunction early in HD is attributable to a correctable defect in the response to BDNF, not its delivery.
    Neuron 07/2014; 83(1):178-188. · 15.77 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Ischemic stroke is one of the leading causes of morbidity and mortality. Treatment options are limited and only a minority of patients receive acute interventions. Understanding the mechanisms that mediate neuronal injury and death may identify targets for neuroprotective treatments. Here we show that the aberrant activity of the protein kinase Cdk5 is a principal cause of neuronal death in rodents during stroke. Ischemia induced either by embolic middle cerebral artery occlusion (MCAO) in vivo or by oxygen and glucose deprivation in brain slices caused calpain-dependent conversion of the Cdk5-activating cofactor p35 to p25. Inhibition of aberrant Cdk5 during ischemia protected dopamine neurotransmission, maintained field potentials, and blocked excitotoxicity. Furthermore, pharmacological inhibition or conditional knock-out (CKO) of Cdk5 prevented neuronal death in response to ischemia. Moreover, Cdk5 CKO dramatically reduced infarctions following MCAO. Thus, targeting aberrant Cdk5 activity may serve as an effective treatment for stroke.
    Journal of Neuroscience 06/2014; 34(24):8259-67. · 6.75 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Cellular diversity and architectural complexity create barriers to understanding the function of the mammalian CNS at a molecular level. To address this problem, we have recently developed a methodology that provides the ability to profile the entire translated mRNA complement of any genetically defined cell population. This methodology, which we termed translating ribosome affinity purification, or TRAP, combines cell type-specific transgene expression with affinity purification of translating ribosomes. TRAP can be used to study the cell type-specific mRNA profiles of any genetically defined cell type, and it has been used in organisms ranging from Drosophila melanogaster to mice and human cultured cells. Unlike other methodologies that rely on microdissection, cell panning or cell sorting, the TRAP methodology bypasses the need for tissue fixation or single-cell suspensions (and the potential artifacts that these treatments introduce) and reports on mRNAs in the entire cell body. This protocol provides a step-by-step guide to implement the TRAP methodology, which takes 2 d to complete once all materials are in hand.
    Nature Protocol 06/2014; 9(6):1282-91. · 8.36 Impact Factor
  • Molecular Psychiatry 03/2014; · 15.15 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Levodopa treatment is the major pharmacotherapy for Parkinson's disease. However, almost all patients receiving levodopa eventually develop debilitating involuntary movements (dyskinesia). Although it is known that striatal spiny projection neurons (SPNs) are involved in the genesis of this movement disorder, the molecular basis of dyskinesia is not understood. In this study, we identify distinct cell-type-specific gene-expression changes that occur in subclasses of SPNs upon induction of a parkinsonian lesion followed by chronic levodopa treatment. We identify several hundred genes, the expression of which is correlated with levodopa dose, many of which are under the control of activator protein-1 and ERK signaling. Despite homeostatic adaptations involving several signaling modulators, activator protein-1-dependent gene expression remains highly dysregulated in direct pathway SPNs upon chronic levodopa treatment. We also discuss which molecular pathways are most likely to dampen abnormal dopaminoceptive signaling in spiny projection neurons, hence providing potential targets for antidyskinetic treatments in Parkinson's disease.
    Proceedings of the National Academy of Sciences 03/2014; · 9.81 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: We have reported previously that autophagy is responsible for amyloid precursor potein-C-terminal fragment (APP-CTF) degradation and therefore Aβ clearance. To elucidate the underlying mechanism, using LC3 affinity purification and mass spectrometry analysis, immunoprecipitation (IP), as well as live imaging analysis, we identified and demonstrated that the adaptor-related protein complex 2 (AP2) and PICALM (phosphatidylinositol binding clathrin assembly protein) are in a complex with LC3 and APP-CTF. Taken together, this new set of data suggests that the AP2-PICALM complex functions as an autophagic cargo receptor for the recognition and shipment of APP-CTF from the endocytic pathway to the LC3-dependent autophagic degradation pathway. Interestingly this AP2-LC3 connection seems to be involved in chemically-induced APP-CTF clearance as we observed using the small compound SMER28. The effect observed following SMER28 was significantly reduced after silencing AP2. While more work is required to elucidate the detailed molecular mechanisms involved, our actual data suggest that there is some level of specificity in the steps mentioned above.
    Autophagy 01/2014; 10(4). · 11.42 Impact Factor
  • Source
  • Source
    Lars Brichta, Paul Greengard
    [Show abstract] [Hide abstract]
    ABSTRACT: Numerous disorders of the central nervous system (CNS) are attributed to the selective death of distinct neuronal cell populations. Interestingly, in many of these conditions, a specific subset of neurons is extremely prone to degeneration while other, very similar neurons are less affected or even spared for many years. In Parkinson's disease (PD), the motor manifestations are primarily linked to the selective, progressive loss of dopaminergic (DA) neurons in the substantia nigra pars compacta (SNpc). In contrast, the very similar DA neurons in the ventral tegmental area (VTA) demonstrate a much lower degree of degeneration. Elucidating the molecular mechanisms underlying the phenomenon of differential DA vulnerability in PD has proven extremely challenging. Moreover, an increasing number of studies demonstrate that considerable molecular and electrophysiologic heterogeneity exists among the DA neurons within the SNpc as well as those within the VTA, adding yet another layer of complexity to the selective DA vulnerability observed in PD. The discovery of key pathways that regulate this differential susceptibility of DA neurons to degeneration holds great potential for the discovery of novel drug targets and the development of promising neuroprotective treatment strategies. This review provides an update on the molecular basis of the differential vulnerability of midbrain DA neurons in PD and highlights the most recent developments in this field.
    Frontiers in Neuroanatomy 01/2014; 8:152. · 4.18 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: The control of motor behavior in animals and humans requires constant adaptation of neuronal networks to signals of various types and strengths. We found that microRNA-128 (miR-128), which is expressed in adult neurons, regulates motor behavior by modulating neuronal signaling networks and excitability. miR-128 governs motor activity by suppressing the expression of various ion channels and signaling components of the extracellular signal-regulated kinase ERK2 network that regulate neuronal excitability. In mice, a reduction of miR-128 expression in postnatal neurons causes increased motor activity and fatal epilepsy. Overexpression of miR-128 attenuates neuronal responsiveness, suppresses motor activity, and alleviates motor abnormalities associated with Parkinson's-like disease and seizures in mice. These data suggest a therapeutic potential for miR-128 in the treatment of epilepsy and movement disorders.
    Science 12/2013; 342(6163):1254-8. · 31.48 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: The hallmarks of Alzheimer's disease (AD) are the aggregates of amyloid-β (Aβ) peptides and tau protein. Autophagy is a major cellular pathway leading to the removal of aggregated proteins. We have reported recently that autophagy was responsible for amyloid precursor protein cleaved C-terminal fragment (APP-CTF) degradation and amyloid β clearance in an Atg5-dependent manner. Here we aimed to elucidate the molecular mechanism by which autophagy mediates the degradation of APP-CTF and the clearance of amyloid β. Through affinity purification followed by mass spectrum analysis, we identified adaptor protein (AP) 2 together with phosphatidylinositol clathrin assembly lymphoid-myeloid leukemia (PICALM) as binding proteins of microtubule-associated protein 1 light chain 3 (LC3). Further analysis showed that AP2 regulated the cellular levels of APP-CTF. Knockdown of AP2 reduced autophagy-mediated APP-CTF degradation. Immunoprecipitation and live imaging analysis demonstrated that AP2 and PICALM cross-link LC3 with APP-CTF. These data suggest that the AP-2/PICALM complex functions as an autophagic cargo receptor for the recognition and shipment of APP-CTF from the endocytic pathway to the LC3-marked autophagic degradation pathway. This molecular mechanism linking AP2/PICALM and AD is consistent with genetic evidence indicating a role for PICALM as a risk factor for AD.
    Proceedings of the National Academy of Sciences 09/2013; · 9.81 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Studies of the multifunctional protein p11 (also known as S100A10) are shedding light on the molecular and cellular mechanisms underlying depression. Here, we review data implicating p11 in both the amplification of serotonergic signalling and the regulation of gene transcription. We summarize studies demonstrating that levels of p11 are regulated in depression and by antidepressant regimens and, conversely, that p11 regulates depression-like behaviours and/or responses to antidepressants. Current and future studies of p11 may provide a molecular and cellular framework for the development of novel antidepressant therapies.
    Nature Reviews Neuroscience 09/2013; · 31.38 Impact Factor
  • Lars Brichta, Paul Greengard, Marc Flajolet
    [Show abstract] [Hide abstract]
    ABSTRACT: For several decades, the dopamine precursor levodopa has been the primary therapy for Parkinson's disease (PD). However, not all of the motor and non-motor features of PD can be attributed solely to dopaminergic dysfunction. Recent clinical and preclinical advances provide a basis for the identification of additional innovative therapeutic options to improve the management of the disease. Novel pharmacological strategies must be optimized for PD by: (i) targeting disturbances of the serotonergic, noradrenergic, glutamatergic, GABAergic, and cholinergic systems in addition to the dopaminergic system, and (ii) characterizing alterations in the levels of neurotransmitter receptors and transporters that are associated with the various manifestations of the disease.
    Trends in Neurosciences 07/2013; · 12.90 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Drugs of abuse, such as cocaine, induce changes in gene expression and epigenetic marks including alterations in histone posttranslational modifications in striatal neurons. These changes are thought to participate in physiological memory mechanisms and to be critical for long-term behavioral alterations. However, the striatum is composed of multiple cell types, including two distinct populations of medium-sized spiny neurons, and little is known concerning the cell-type specificity of epigenetic modifications. To address this question we used bacterial artificial chromosome transgenic mice, which express EGFP fused to the N-terminus of the large subunit ribosomal protein L10a driven by the D1 or D2 dopamine receptor (D1R, D2R) promoter, respectively. Fluorescence in nucleoli was used to sort nuclei from D1R- or D2R-expressing neurons and to quantify by flow cytometry the cocaine-induced changes in histone acetylation and methylation specifically in these two types of nuclei. The two populations of medium-sized spiny neurons displayed different patterns of histone modifications 15 min or 24 h after a single injection of cocaine or 24 h after seven daily injections. In particular, acetylation of histone 3 on Lys 14 and of histone 4 on Lys 5 and 12, and methylation of histone 3 on Lys 9 exhibited distinct and persistent changes in the two cell types. Our data provide insights into the differential epigenetic responses to cocaine in D1R- and D2R-positive neurons and their potential regulation, which may participate in the persistent effects of cocaine in these neurons. The method described should have general utility for studying nuclear modifications in different types of neuronal or nonneuronal cell types.
    Proceedings of the National Academy of Sciences 05/2013; · 9.81 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: p11, through unknown mechanisms, is required for behavioral and cellular responses to selective serotonin reuptake inhibitors (SSRIs). We show that SMARCA3, a chromatin-remodeling factor, is a target for the p11/annexin A2 heterotetrameric complex. Determination of the crystal structure indicates that SMARCA3 peptide binds to a hydrophobic pocket in the heterotetramer. Formation of this complex increases the DNA-binding affinity of SMARCA3 and its localization to the nuclear matrix fraction. In the dentate gyrus, both p11 and SMARCA3 are highly enriched in hilar mossy cells and basket cells. The SSRI fluoxetine induces expression of p11 in both cell types and increases the amount of the ternary complex of p11/annexin A2/SMARCA3. SSRI-induced neurogenesis and behavioral responses are abolished by constitutive knockout of SMARCA3. Our studies indicate a central role for a chromatin-remodeling factor in the SSRI/p11 signaling pathway and suggest an approach to the development of improved antidepressant therapies. PAPERCLIP:
    Cell 02/2013; 152(4):831-43. · 31.96 Impact Factor
  • Paul Greengard, Eric J Nestler
    [Show abstract] [Hide abstract]
    ABSTRACT: Introduction Paul Greengard was born in New York City in 1925. After completing high school, he served three years in the US Navy during World War II and then completed his bachelor's degree at Hamilton College where he majored in physics and mathematics. He obtained a PhD in biophysics from Johns Hopkins University in 1953 and pursued postdoctoral training with Wilhelm Feldberg at the National Institute for Medical Research in England. After eight years as head of biochemistry at Geigy, and sabbaticals at Albert Einstein College of Medicine and Vanderbilt University, he joined the Yale University faculty as a full professor of pharmacology in 1968. While he was at Yale, Greengard's laboratory performed groundbreaking research, which demonstrated a role for cyclic nucleotides, protein kinases and protein phosphatases, and their protein substrates in the regulation of synaptic transmission. In 1983, Greengard moved to The Rockefeller University, where he has since served as the Vincent Astor Professor and Head of the Laboratory of Molecular and Cellular Neuroscience. Greengard's paradigm-shifting research has continued at Rockefeller and has informed our understanding and possible treatment of a host of brain disorders, including schizophrenia, Alzheimer's disease, Parkinson's disease, and depression. He is the author of more than 950 research articles and reviews. Greengard has received numerous awards and honors, including the Nobel Prize in Physiology or Medicine in 2000, the Metropolitan Life Foundation Award for Medical Research, The National Academy of Sciences Award in Neuroscience, the Ralph W. Gerard Prize in Neuroscience for the Society for Neuroscience, and the Karolinska Institutet's Bicentennial Gold Medal. He is a member of the US National Academy of Sciences and the Institute of Medicine of the National Academies. The following interview was conducted on May 29, 2012.
    Annual Review of Pharmacology 01/2013; 53:1-16. · 21.54 Impact Factor

Publication Stats

58k Citations
7,256.54 Total Impact Points


  • 1983–2014
    • The Rockefeller University
      • • Laboratory of Molecular and Cellular Neuroscience
      • • Laboratory of RNA Molecular Biology
      New York City, New York, United States
  • 2004–2013
    • French Institute of Health and Medical Research
      • Institut du Fer à Moulin U839
      Lutetia Parisorum, Île-de-France, France
    • Ludwig-Maximilian-University of Munich
      • Anatomical Institute
      München, Bavaria, Germany
    • Athens State University
      Athens, Alabama, United States
  • 1998–2012
    • Northwestern University
      • • Department of Physiology
      • • Department of Cell and Molecular Biology
      Evanston, IL, United States
    • Université Libre de Bruxelles
      Bruxelles, Brussels Capital Region, Belgium
  • 1988–2012
    • Karolinska Institutet
      • • Institutionen för neurovetenskap
      • • Institutionen för fysiologi och farmakologi
      Solna, Stockholm, Sweden
    • Cardiff University
      • Department of Physiology
      Cardiff, WLS, United Kingdom
  • 1970–2012
    • Yale University
      • • Department of Pharmacology
      • • Child Study Center
      • • Department of Psychiatry
      • • Department of Cell Biology
      • • Department of Molecular Biophysics and Biochemistry
      New Haven, CT, United States
  • 2011
    • Ewha Womans University
      • School of Medicine
      Seoul, Seoul, South Korea
  • 2010
    • Mount Sinai School of Medicine
      • Department of Pharmacology and Systems Therapeutics
      Manhattan, New York, United States
  • 2009
    • Xiamen University
      Amoy, Fujian, China
    • Okinawa Institute of Science and Technology
      Okinawa, Okinawa, Japan
  • 2004–2008
    • Duke University Medical Center
      • Department of Neurobiology
      Durham, NC, United States
    • Royal College of Surgeons in Ireland
      • • Department of Molecular and Cellular Therapeutics
      • • Department of Clinical Pharmacology
      Dublin, L, Ireland
  • 2006–2007
    • University of Texas Southwestern Medical Center
      • Department of Psychiatry
      Dallas, TX, United States
    • Intra-Cellular Therapies, Inc.
      New York City, New York, United States
  • 2005–2007
    • Uppsala University
      • The Rudbeck Laboratory
      Uppsala, Uppsala, Sweden
  • 2003–2006
    • Vanderbilt University
      • Department of Pharmacology
      Nashville, Michigan, United States
    • RIKEN
      • Brain Science Institute (BSI)
      Wako, Saitama-ken, Japan
  • 2004–2005
    • Emory University
      • Department of Psychiatry and Behavioral Sciences
      Atlanta, GA, United States
  • 1999–2005
    • Kurume University
      • • Department of Pharmacology
      • • Department of Physiology
      Куруме, Fukuoka, Japan
  • 2002–2004
    • Station Biologique de Roscoff
      Rosko, Brittany, France
    • Nicox Research Institute
      Nice, Provence-Alpes-Côte d'Azur, France
  • 2000–2004
    • Università degli Studi di Genova
      • Dipartimento di Medicina sperimentale (DIMES)
      Genova, Liguria, Italy
    • Ospedale di San Raffaele Istituto di Ricovero e Cura a Carattere Scientifico
      • Division of Neuroscience
      Milano, Lombardy, Italy
    • University of Oslo
      • Institute of Basic Medical Sciences
      Oslo, Oslo, Norway
  • 1994–2004
    • Florida State University
      • • Department of Biomedical Sciences
      • • Department of Psychology
      • • Program in Neuroscience
      Tallahassee, FL, United States
  • 1999–2000
    • The University of Tokyo
      • Department of Pharmaceutical Sciences
      Tokyo, Tokyo-to, Japan
  • 1995–2000
    • University of Rome Tor Vergata
      • Dipartimento di Dirito Pubblico
      Roma, Latium, Italy
    • The Graduate University for Advanced Studies
      Миура, Kanagawa, Japan
    • Columbia University
      • Department of Biological Sciences
      New York City, NY, United States
    • University of Tennessee
      • Department of Anatomy and Neurobiology
      Knoxville, TN, United States
  • 1995–1998
    • Collège de France
      • Center for Interdisciplinary Research in Biology
      Lutetia Parisorum, Île-de-France, France
  • 1983–1998
    • Cornell University
      • • Department of Neurology and Neuroscience
      • • School of Applied and Engineering Physics
      Ithaca, NY, United States
  • 1992–1995
    • San Raffaele Scientific Institute
      Milano, Lombardy, Italy
  • 1990–1994
    • Howard Hughes Medical Institute
      Ashburn, Virginia, United States
  • 1993
    • University of Bologna
      • Department of Biomedical Science and Neuromotor Sciences DIBINEM
      Bologna, Emilia-Romagna, Italy
    • Boston University
      • Health Sciences
      Boston, MA, United States
  • 1990–1993
    • National Research Council
      Roma, Latium, Italy
  • 1989–1993
    • University of Milan
      • Center of Cytopharmacology CNR
      Milano, Lombardy, Italy
    • Lund University
      • Department of Biophysical Chemistry
      Lund, Skane, Sweden
  • 1968–1992
    • Yale-New Haven Hospital
      New Haven, Connecticut, United States
  • 1990–1991
    • Marine Biological Laboratory
      Falmouth, Massachusetts, United States
  • 1988–1990
    • CUNY Graduate Center
      New York City, New York, United States