Researcher

    Graziella Di Cristo , Ph.D.

    graziella.dicristo@recherche-ste-justine.qc.ca
    Graziella Di Cristo
    Research Axis
    Brain and Child Development
    Research Theme
    Neurodevelopmental diseases
    Address
    CHUSJ

    Phone
    514 345-4931 #2867

    Fax
    514 345-4801

    Title

    Internship opportunity(ies)

    Education

    • Postdoctoral Fellow in Neuroscience, Cold Spring Harbor Laboratory, NY, USA, 2001-2006.
    • PhD in Neuroscience, University of Pisa, Italy, 1998-2001.

    Research Interests

    In the cerebral cortex, neural networks consist of two broad classes of neurons: excitatory projection neurons, which use glutamate as neurotransmitter, and inhibitory local-circuit interneurons, comprising about 20-30% of all cortical neurons, which primarily use gamma-aminobutyric acid-GABA as a neurotransmitter. Although a minor cell population compared to glutamatergic neurons, GABAergic interneurons play a vital role in modulating neuronal excitability and integration, and in the generation of temporal synchrony and oscillations among networks of glutamatergic neurons. In addition, the development of GABAergic inhibition has recently been shown to play a key role in critical period plasticity of cortical circuits. Critical periods represent epochs of heightened brain plasticity during which experience can produce permanent, large-scale changes in neuronal circuits. By regulating critical period plasticity, GABAergic interneurons may influence how experience shapes the brain during early life and adolescence. To date our understanding of the molecular mechanisms regulating GABAergic synapse development is still in its infancy.

    Disruption of the balance between excitatory and inhibitory synaptic activities is believed to cause diseases such as epilepsy, autism and schizophrenia. Alteration in the maturation of the GABAergic network thus might be a critical determinant of these neurodevelopmental disorders. Understanding the cellular and molecular mechanisms governing GABAergic circuit development is the first essential step towards a better comprehension of how abnormalities in this process can occur, thereby leading to aberrant cortical development and function. The overall goal of my laboratory is to study the molecular mechanisms regulating GABAergic synapse development, by using a combination of molecular, imaging and electrophysiological techniques.

    We currently focus on the following three questions:

    • Molecular pathways regulating GABAergic synapse maturation in the postnatal brain;
    • Mechanisms linking experience to GABAergic synapse maturation in primary visual cortex;
    • Alterations of GABAergic circuit development in animal models of neurodevelopment diseases (e.g. epilepsy).

    Awards and Distinctions

    • Canada Research Chair in Neural Circuit Development, Tier 2, 2006-2011.
    • Young Investigator Award, National Alliance for Research on Schizophrenia and Depression (NARSAD), 2007-2009.
    • Young Investigator Award, NARSAD, 2004-2006.
    • Postdoctoral Fellowship, European Molecular Biology Organization, 2002-2004.
    • Graduate Fellowship, Scuola Normale Superiore, 1997-2000.

    Most Important Publications

    1. Di Cristo G, Chattopadhyaya B, Kuhlman SJ, Fu Y, Bélanger M-C*, Wu CZ Rutishauser U, Maffei L, Huang ZJ (2007). Activity-dependent PSA expression promotes the maturation of GABA inhibition and the onset of critical period plasticity. Nature Neuroscience,10:1569-1577.
    1. Gibbs SA*, Chattopadhyaya B*, Desgent S, Awad PN, Clerk-Lamalice O, Levesque M, Vianna RM, Rébillard RM, Delsemme AA, Hébert D, Tremblay L, Descarries L, Lepage M, Di Cristo  G, Carmant L (2011). Long-term consequences of a prolonged febrile seizure in a dual pathology model. Neurobiology of Diseases, 43(2):312-21. * equal contribution
    1. Bélanger M-C, Di Cristo G (2011). Sensory experience differentially modulates the mRNA expression of the polysialyltransferases ST8SiaII and ST8SiaIV in postnatal mouse visual cortex. PloSOne, 2011;6(9):e24874.
    1. Baho E, Di Cristo G (2012). Synaptic activity is required for the maintenance of GABAergic innervation patterns in the cortex. Journal of Neuroscience 32:911-8.
    1. Chattopadhyaya B, Baho E, Schachner M, Huang JZ, Di Cristo G (2013). NCAM-mediated Fyn signaling promotes perisomatic GABAergic synapse maturation in adolescent cortex. Journal of Neuroscience, 33:5957-68.
    1. Berryer MH, Hamdan FF, KlittenLL, Møller RS, Carmant L, Patry P, Dobrzeniecka S, Rochefort D, Neugnot M, Lacaille JC, Niu Z, Eng CM, Yang Y, Palardy S, Céline Belhumeur C, Rouleau GA, Tommerup N, Immken LD, Beauchamp M, Simpson Patel G, Scheffzek K, Hjalgrim H, Michaud JL, Di Cristo G (2013). Mutations in SYNGAP1 cause intellectual disability, autism and a specific form of epilepsy by inducing haploinsufficiency. Human Mutations 34:385-94.
    1. Lachance-Touchette P*, Choudhury M*, Stoica A, Di Cristo G, Cossette P (2014). Single-cell genetic expression of mutant GABAA receptors causing Human genetic epilepsy alters dendritic spine and GABAergic bouton formation in a mutation-specific manner. Front Cell Neurosci. 2014 Oct 14;8:317. doi: 10.3389/fncel.2014.00317. * equal contribution.
    1. Awad PN, Sanon N, Chattopadhyaya B, Carriço JN, Ouardouz M, Gagné J, Duss S, Wolf D, Desgent S, Cancedda L, Carmant L, Di Cristo G (2016). Reducing premature KCC2 expression rescues seizure susceptibility and spine morphology in atypical febrile seizures. .Neurobiology of Diseases, 91:10-20.
    1. Berryer MH, Chattopadhyaya B, Xing P, Antoine-Bertrand J, Lévesque M, Sanon N, Bosoi C, Fadi F, Hamdan FF, Boucher B, Carmant L, Avoli M, Lamarche-Vane N, Lacaille J-C, Michaud JL, Di Cristo G (2016). Syngap1 deficit in GABAergic cells impairs synaptic development, functional inhibition and cognitive abilities. Nature Communications, 7:13340

Publications

Mutations in SYNGAP1 cause intellectual disability, autism, and a specific form of epilepsy by inducing haploinsufficiency - Berryer MH, Hamdan F, Klitten LL, Moller RS, Carmant L, Schwartzentruber JA, Patry L, Dobrzeniecka S, Rochefort D, Neugnot-Cerioli M, Lacaille JC, Niu Z, Eng CM, Yang Y, Palardy S, Belhumeur C, Rouleau GA, Tommerup N, Immken L, Beauchamp MH, Patel GS, Majewski J, Tarnopolsky MA, Scheffzek K, Hjalgrim H, Michaud JL, Di Cristo G. Mutations in SYNGAP1 cause intellectual disability, autism, and a specific form of epilepsy by inducing haploinsufficiency. Hum Mutat 2013; 34(2): 385-394.

GABAergic circuit dysfunctions in neurodevelopmental disorders - Chattopadhyaya B, Di Cristo G. GABAergic circuit dysfunctions in neurodevelopmental disorders. Front Mol Psychiatry 2012; (sous presse).

Neural activity and neurotransmission regulate the maturation of the innervation field of cortical GABAergic interneurons in an age-dependent manner - Baho E, Di Cristo G. Neural activity and neurotransmission regulate the maturation of the innervation field of cortical GABAergic interneurons in an age-dependent manner. J Neurosci 2012; 32(3): 911-918.

Expanded ATXN3 frameshifting events are toxic in Drosophila and mammalian neuron models - Stochmanski SJ, Therrien M, Laganière J, Rochefort D, Laurent S, Karemera L, Gaudet R, Vyboh K, Van Meyel DJ, Di Cristo G, Dion PA, Gaspar C, Rouleau GA. Expanded ATXN3 frameshifting events are toxic in Drosophila and mammalian neuron models. Hum Mol Genet 2012; 21(10): 2211-2218.

GABA signaling promotes synapse elimination and axon pruning in developing cortical inhibitory interneurons - Wu X, Fu Y, Knott G, Lu J, Di Cristo G, Huang ZJ. GABA signaling promotes synapse elimination and axon pruning in developing cortical inhibitory interneurons. J Neurosci 2012; 32(1): 331-343.

GABAergic circuit development and its implication for CNS disorders - Di Cristo G, Pizzorusso T, Cancedda L, Sernagor E. GABAergic circuit development and its implication for CNS disorders. Neural Plast 2011; 2011: 623705 (on line).

Molecular factors controlling inhibitory circuit maturation and onset of critical period plasticity: implications for developmental diseases - Di Cristo G, Chattopadhyaya B. Molecular factors controlling inhibitory circuit maturation and onset of critical period plasticity: implications for developmental diseases. Dans: Chalupa LM, Berardi N, Caleo M, Galli-Resta L (eds). Brain plasticity: new perspectives. MIT press, 2011; 101-111.

Sensory experience differentially modulates the mRNA expression of the polysialyltransferases ST8SiaII and ST8SiaIV in postnatal mouse visual cortex - Bélanger M-C, Di Cristo G. Sensory experience differentially modulates the mRNA expression of the polysialyltransferases ST8SiaII and ST8SiaIV in postnatal mouse visual cortex. PLoS ONE 2011; (9): e24874.

Long-term consequences of a prolonged febrile seizure in a dual pathology model - Gibbs S, Chattopadhyaya B, Desgent S, Awad P, Clerk-Lamalice O, Lévesque M, Vianna RM, Rébillard RM, Delsemme AA, Hébert D, Tremblay L, Lepage M, Descarries L, Di Cristo G, Carmant L. Long-term consequences of a prolonged febrile seizure in a dual pathology model. Neurobiol Dis 2011; 43(2): 312-321.

N-methyl-D-aspartate, hyperpolarization-activated cation current (Ih) and gamma-aminobutyric acid conductances govern the risk of epileptogenesis following febrile seizures in rat hippocampus - Ouardouz M, Lema P, Awad P, Di Cristo G, Carmant L. N-methyl-D-aspartate, hyperpolarization-activated cation current (Ih) and gamma-aminobutyric acid conductances govern the risk of epileptogenesis following febrile seizures in rat hippocampus. Eur J Neurosci 2010; 31(7): 1252-1260.

Reducing intracortical inhibition in the adult visual cortex promotes ocular dominance plasticity - Harauzov A, Spolidoro M, Di Cristo G, De Pasquale R, Cancedda L, Pizzorusso T, Viegi A, Berardi N, Maffei L. Reducing intracortical inhibition in the adult visual cortex promotes ocular dominance plasticity. J Neurosci 2010; 30(1): 361-371.

Mice doubly-deficient in lysosomal hexosaminidase A and neuraminidase 4 show epileptic crises and rapid neuronal loss - Seyrantepe V, Lema P, Caqueret A, Dridi L, Bel Hadj S, Carpentier S, Boucher F, Levade T, Carmant L, Gravel R, Hamel E, Vachon P, Di Cristo G, Michaud JL, Morales C, Pshezhetsky AV. Mice doubly-deficient in lysosomal hexosaminidase A and neuraminidase 4 show epileptic crises and rapid neuronal loss. PLoS Genet 2010; 6(9): pii: e1001118.

Transient neurites of retinal horizontal cells exhibit columnar tiling via homotypic interactions - Huckfeldt RM, Schubert T, Morgan JL, Godinho L, Di Cristo G, Huang ZJ, Wong RO. Transient neurites of retinal horizontal cells exhibit columnar tiling via homotypic interactions. Nature Neurosci 2009; 12(1): 35-43.

Time to change: retina sends a messenger to promote plasticity in visual cortex - Huang ZJ, Di Cristo G. Time to change: retina sends a messenger to promote plasticity in visual cortex. Neuron 2008; 59(3): 355-358.

Development of cortical GABAergic circuits and its implications for neurodevelopmental disorders - Di Cristo G. Development of cortical GABAergic circuits and its implications for neurodevelopmental disorders. Clin Genet 2007; 72(1): 1-8.

Activity-dependent PSA expression regulates inhibitory maturation and onset of critical period plastic - Di Cristo G, Chattopadhyaya B, Kuhlman S, Fu Y, Bélanger M-C, Wu CZ, Rutishauser U, Maffei L, Huang ZJ. Activity-dependent PSA expression regulates inhibitory maturation and onset of critical period plastic. Nature Neurosci 2007; 10(12): 1569-1577.

GAD67-mediated GABA synthesis and signaling regulate inhibitory synaptic innervation in the visual cortex - Chattopadhyaya B, Di Cristo G, Wu CZ, Knott G, Kuhlman S, Fu Y, Palmiter RD, Huang ZJ. GAD67-mediated GABA synthesis and signaling regulate inhibitory synaptic innervation in the visual cortex. Neuron 2007; 54(6): 889-903.

Development of GABA innervation in the cerebral and cerebellar cortices - Huang ZJ, Di Cristo G, Ango F. Development of GABA innervation in the cerebral and cerebellar cortices. Nat Rev Neurosci 2007; 8(9): 673-686.

Differential effects of NT-4, NGF and BDNF on development of neurochemical architecture and cell size regulation in rat visual cortex during the critical period - Enghelhardt M, Di Cristo G, Berardi M, Maffei HV, Wahle P. Differential effects of NT-4, NGF and BDNF on development of neurochemical architecture and cell size regulation in rat visual cortex during the critical period. Eur J Neurosci 2007; 25(2): 529-540.

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Created on 9/18/2014
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