Cortical Circuits in Health and Disease
Bridging the gaps between basic and translational neurobiology The cortex is the most complex and developed region of the brain. Higher cognitive functions, memories, emotions, they all depend on the proper formation and function of cortical circuits. Alterations of cortical wiring at neuritic or synaptic level underlie different brain pathologies: i) neurodevelopmental disorders, such as Schizophrenia; ii) neurodegenerative disorders, such as Alzheimer's Disease; iii) acute brain injuries provoked, for instance, by stroke or cerebral trauma.
Our aim is to understand the structure and function of cortical circuits in physiological and pathological conditions. Specifically, we investigate the role of disease-linked genes in the development and connectivity of excitatory/inhibitory cortical neurons using state-of-the-art approaches such as genetic, molecular neurobiology, morpho-functional analysis and electrophysiology.
In last years, we determined role of the schizophrenia risk-gene NRG1 in excitatory/inhibitory neurons2,3,4. Currently, we are investigating the molecular signalling underlying NRG1 function to identify the effectors of this gene and new therapeutic targets to treat Schizophrenia.
Another long term goal of the lab is to apply our knowledge on circuit development to study neuronal regeneration in the adult: we develop new approaches in vitro and in vivo to discover new treatments that can help recovery of cortical function upon stroke or brain injuries
PLD3 gene and processing of APP.
Fazzari P, Horre K, Arranz AM, Frigerio CS, Saito T, Saido TC, De Strooper B
Nature , 2017 Jan 25, vol. 541, pag. E1-E2
Cell autonomous regulation of hippocampal circuitry via Aph1b-?-secretase/neuregulin 1 signalling.
Fazzari P, Snellinx A, Sabanov V, Ahmed T, Serneels L, Gartner A, Shariati SA, Balschun D, De Strooper B
eLife , 2014 Jun 2, vol. 3
Nrg1 reverse signaling in cortical pyramidal neurons.
Pedrique SP, Fazzari P
The Journal of neuroscience : the official journal of the Society for Neuroscience , 2010 Nov 10, vol. 30, pag. 15005-6, Impact Factor: 7.271
Control of cortical GABA circuitry development by Nrg1 and ErbB4 signalling.
Fazzari P, Paternain AV, Valiente M, Pla R, Luján R, Lloyd K, Lerma J, Marín O, Rico B
Nature , 2010 Apr 29, vol. 464, pag. 1376-80, Impact Factor: 36.104
Plexin-B1 plays a redundant role during mouse development and in tumour angiogenesis.
Fazzari P, Penachioni J, Gianola S, Rossi F, Eickholt BJ, Maina F, Alexopoulou L, Sottile A, Comoglio PM, Flavell RA, Tamagnone L
BMC developmental biology , 2007 May 22, vol. 7, pag. 55