Pr. Pierre VANDERHAEGHEN
Directeur de recherche au VIB-KU Leuven Center for Brain & Disease Research.
THÈME DE RECHERCHE :
« Mechanisms of plasticity following transplantation of human neurons in the mouse neonatal visual cortex. »
SUBVENTION JED : 42.000 €
OBJECTIF DU PROJET :
Le principal objectif de recherche de son laboratoire est de comprendre les mécanismes moléculaires et cellulaires qui sous-tendent le développement et l'évolution du cortex cérébral, des cellules souches aux circuits neuronaux, de la souris à l'homme, en matière de santé et de maladie.
Neural circuit assembly is characterized by critical periods of plasticity, in which experience- dependent remodeling acts to refine neuronal circuits. Plasticity subsequently decreases during adulthood, and circuits gradually lose their capacity to adapt to environmental changes or brain insult. A better understanding of the mechanisms underlying plasticity induction, and loss, have major implications for brain diseases and their treatments, most strikingly for visual defects of central origin.
Our lab has demonstrated recently that human cortical pyramidal neurons, generated from embryonic stem cells (ESC) and xenotransplanted as single cells in the mouse neonatal cortex, develop along their species-specific protracted period, so that they retain juvenile features such as dynamic dendritic spines, even in 3-6 months-old mice. Following this protracted development, the human neurons transplanted in the visual cortex integrate functionally within the host circuits to display physiological responses tuned to specific visual stimuli.
These recent data open the exciting possibility that transplanted human neurons, thanks to their long-term retention of juvenile properties while connecting to the host, could increase the functional plasticity of the adult mouse circuits. On the other hand it raises the fascinating question of the plasticity of the human neurons themselves, which would constitute a unique experimental model of human neural plasticity in vivo.
Here we will test whether the xenotransplantation of human cortical neurons in the neonatal mouse visual cortex can impact on the plasticity of the host cortical circuits, more specifically on visual plasticity, and explore the underlying cellular and molecular mechanisms.
On the other hand we will test whether the human neurons themselves display juvenile-like visual plasticity.
This project, which is new to our laboratory that usually focuses on early brain development, draws on the latest knowledge and technology in distinct disciplines from human stem cell technology, to developmental neurobiology and in vivo imaging of visual plasticity. We hope that it will generate a novel framework for the study of neuronal plasticity and will bring novel insights to our understanding of human-specific experience-dependent brain development. Moreover it may have, in the long-run, important relevance for our understanding and treatment of conditions of the visual system like amblyopia, but also more broadly for processes like learning and memory defects following genetic or environmental insult to the developing brain.