Researcher

Title

• Head Co-Deputy, Research Axis - Brain and Child Development, CHU Sainte-Justine
• Professor, Department of Neurosciences, Université de Montréal (2018)
• Co-Chief, Pole of Excellence - Brain and Child Development, CHU Sainte-Justine (2017)

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

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 autism and epilepsy. 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, electrophysiological and behavioural 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.

• Neurodevelopment
• GABAergic circuits
• Synapse formation
• Synaptic plasticity
• Microscopy (confocal and multiphoton microscopy, live imaging)
• Cognitive tests in animal models
• Electrophysiology

Awards and Distinctions

• Canada Research Chair in Neural Circuit Development, Tier 2, 2006-2011, 2011-2016
• 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

Major Financing

• Canadian Institutes of Health Research
• Natural Sciences and Engineering Research Council of Canada
• Heart and Stroke Foundation of Canada

Presentations

• Gordon Research Conference on Inhibition in CNS, Les Diablerets, Suisse, June 2017
• Advanced PhD Summer School, Utrecht, Pays-Bas, July 2017
• University of North CarolinOctober 2017
• 18th International Fragile X and Early-Onset Cognitive Disorders Workshop, Hôtel Sacacomie, Saint-Alexis-des-Monts, QC, Canada, October 2017
• EMBO Meeting “Cortical interneurons in health and disease”, Mallorca, Spain, June 2018

Publications

Di Cristo Lab Selected Publications

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.
2. Chattopadhyaya B, Di Cristo G (2012). GABAergic circuit dysfunctions in neurodevelopmental disorders. Frontiers in Psychiatry. 3:51
3. 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.
4. 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. * corresponding authors
5. 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.
6. 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. Neurobiol Dis, 91:10-20.
7. Berryer MH, Chattopadhyaya B, Xing P, Antoine-Bertrand J, Fadi F, Hamdan FF, Boucher B, Lamarche-Vane N, Lacaille J-C, Michaud JL, Di Cristo G (2016). Syngap1 deficit in GABAergic cells impairs inhibitory synapse development, synaptic inhibition and cognitive function.  Nature Communications, 7:13340.
8. Di Cristo G, Awad PN, Hamidi S, Avoli M (2018). KCC2, Epileptiform Synchronization and Epileptic Disorders. Progress in Neurobiology, 162,1-16.
9. Awad PN, Amegandjin CA, Szczurkowska J, Nunes-Carriço J, Baho E, Cancedda L, Carmant L, Di Cristo G (2018). The effects of KCC2 on dendritic spine formation are cortical-region and BDNF dependent. Cerebral Cortex, 28, 4049-4062.
10. Baho E&, Chattopadhyaya B&, Lavertu-Jolin M&, Mazziotti R, Awad PN, Chehrazi P, Groleau M, Jahannault-Talignani C, Sanon NT, Vaucher E, Ango F, Pizzorusso T, Baroncelli L, Di Cristo G (2019). P75 Neurotrophin Receptor regulates the timing of maturation of cortical parvalbumin cell connectivity and promotes ocular dominance plasticity in adult visual cortex. Journal of Neuroscience, 39:4489-4510.& equally contributing authors.
11. Patrizi A, Awad PN&, Chattopadhyaya B&, Di Cristo G, Fagiolini M (2020). Accelerated hyper-maturation of parvalbumin circuits in the absence of MeCP2. Cerebral Cortex, 30. 256-268. & equally contributing authors.
12. Parent-Vachon M, Beaudry F, Carrier D, Di Cristo G, Vachon P, (2019). The Effects of Exercise on Pain and Reproductive Performance in Female Pregnant Mice With Neuropathic Pain. Biol Res Nurs, 21:500-509.
13. Amegandjin CA&, Choudhury M&, Jadhav V, Nunes-Carrico J, Quintal A, Berryer MH, Snapyan M, Chattopadhyaya B, Saghatelyan A, Di Cristo G (2021). Sensitive period for rescuing parvalbumin interneurons connectivity and social behavior deficits caused by TSC1 loss. Nature Communications,12:3653. & equally contributing authors.
14. Pará C, Bose P, Bruno L, Freemantle E, Taherzadeh M, Pan X, Han C, McPherson PS, Lacaille JC, Bonneil É, Thibault P, O'Leary C, Bigger B, Morales CR, Di Cristo G, Pshezhetsky AV (2021). Early defects in mucopolysaccharidosis type IIIC disrupt excitatory synaptic transmission. JCI Insight, 6(15):e142073.
15. Munguba H, Chattopadhyaya B, Nilsson S, Carriço JN, Memic F, Oberst P, Batista-Brito R, Muñoz-Manchado AB, Wegner M, Fishell G, Di Cristo G*, Hjerling-Leffler J* (2021). Postnatal Sox6 Regulates Synaptic Function of Cortical Parvalbumin-Expressing Neurons. Journal of Neuroscience, 41:8876-86. * corresponding authors.
16. Mirabella F, Desiato G, Mancinelli S, Fossati G, Rasile M, Morini R, Markicevic M, Grimm C, Amegandjin C, Termanini A, Peano C, Kunderfranco P, Di Cristo G, Zerbi V, Menna E, Lodato S, Matteoli M, Pozzi D (2021). Prenatal interleukin 6 elevation increases glutamatergic synapse density and disrupts hippocampal connectivity in offspring. Immunity, 54:2611-31.
17. Shaker T, Chattopadhyaya B, Amilhon B, Di Cristo G, Weil AG (2021). Transduction of inflammation from peripheral immune cells to the hippocampus induces neuronal hyperexcitability mediated by Caspase-1 activation. Neurobiol Dis, 160:105535.
18. Carreño-Muñoz MI, Chattopadhyaya B, Agbogba K, Côté V, Wang S, Lévesque M, Avoli M, Michaud JL, Lippé S, Di Cristo G (2022). Sensory processing dysregulations as reliable translational biomarkers in SYNGAP1 haploinsufficiency. Brain, 145:754-769.
19. Cherubini E, Di Cristo G, Avoli M (2022). Dysregulation of GABAergic Signaling in Neurodevelomental Disorders: Targeting Cation-Chloride Co-transporters to Re-establish a Proper E/I Balance. Frontiers Cellular Neuroscience, 15:813441.
20. Wolf DC, Sanon NT, Cunha AOS, Chen JS, Shaker T, Elhassan AR, do Nascimento ASF, Di Cristo G, Weil AG (2022). Sex-specific differences in KCC2 localisation and inhibitory synaptic transmission in the rat hippocampus. Science Reports, 12:3186.
21. Khlaifia A, Jadhav V, Danik M, Badra T, Berryer M, Dionne-Laporte A, Chattopadhyaya B, Di Cristo G, Lacaille JC, Michaud JL (2023). Syngap1 disruption induced by recombination between inverted loxP sites is associated with hippocampal interneuron dysfunction. eNeuro, 10(5):ENEURO.0475-22.2023.
22. Lavertu-Jolin M, Chattopadhyaya B, Chehrazi P, Carrier D, Wünnemann F, Leclerc S, Dumouchel F, Robertson D, Affia H, Saba K, Gopal V, Patel AB, Andelfinger G, Pineyro G, Di Cristo G (2023). Acan downregulation in parvalbumin GABAergic cells reduces spontaneous recovery of fear memories. Molecular Psychiatry, 28:2946-63.
23. Chehrazi P, Lee K, Lavertu-Jolin M, Abbasnejad Z, Carreño-Muñoz MI, Chattopadhyaya B, Di Cristo G (2023). The p75 Neurotrophin Receptor in Preadolescent Prefrontal Parvalbumin Interneurons Promotes Cognitive Flexibility in Adult Mice. Biological Psychiatry, 94:310-21.
24. Lee KKY, Chattopadhyaya B, do Nascimento ASF, Moquin L, Rosa-Neto P, Amilhon B*, Di Cristo G* (2024). Neonatal hypoxia impairs serotonin release and cognitive functions in adult mice. Neurobiol Dis. 193:106465. *corresponding authors
    
    Complete publication list: https://www.ncbi.nlm.nih.gov/myncbi/graziella.di%20cristo.1/bibliography/public/