Researcher

Title

• Head Deputy, Research Axis - Brain and Child Development, CHU Sainte-Justine
• Associate Professor, Department of Neurosciences, Université de Montréal, 2012
• Chairholder, Canada Research Chair in Neural Circuit Development, 2006
• Co-Chief, Pole of Excellence - Brain and Child Development, CHU Sainte-Justine, 2017

Laboratory

Neural circuits: roles and effects on brainpower

• 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

1. 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.
2. 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
3. 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.
4. 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.
5. 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.
6. Harauzov A*, Spolidoro M*, Di Cristo G*, DePasquale R, Cancedda L, Pizzorusso T, Viegi A, Berardi N, Maffei L (2010). Reducing intracortical inhibition in the adult visual cortex promotes ocular dominance plasticity. Journal of Neuroscience. 30:361-71. * equal contribution
7. 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. Science Editors’ Choice STKE December (2007), 318:1699.
8. Chattopadhyaya B, Di Cristo G, Wu CZ, Knott G, Kuhlman SJ, Fu Y, Palmiter RD, Huang ZJ (2007).  Regulation of GABAergic axon branching and synaptic innervation by GAD67-mediated GABA synthesis and signaling. Neuron, 54: 889-903.
9. Di Cristo G, Wu C, Chattopadhyaya B, Ango F, Higashiyama H, Svoboda K, Huang ZJ. (2004).  Subcellular domain-restricted GABAergic innervation in primary visual cortex in the absence of sensory and thalamic inputs.  Nature Neuroscience, 7:1184-1186.
10. Chattopadhyaya B*, Di Cristo G*, Higashiyama H, Knott GW, Welker E,  Huang  ZJ. (2004). Activity and experience-dependent maturation of perisomatic GABAergic innervation in primary visual cortex during a postnatal critical period.  Journal of Neuroscience 24:9598-9611. * equal contribution.