Neurocentre Magendie

Guillaume BONY




Post-Doctorant

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Cursus:
Doctorat, Institut Italien de Technologie, Gênes (2011)
Postdoc, Neurocentre Magendie (2012)

Expertise: Corctical Circuitry, Patch-clamp in vivo, Fragile X Syndrome, Sensorial systems, Cell biology



  



7 publication(s) depuis Janvier 2010:


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* equal contribution
Les IF indiqués ont été collectés par le Web of Sciences en


08/12/2014 | Nat Neurosci   IF 16.7
Early depolarizing GABA controls critical-period plasticity in the rat visual cortex.
Deidda G, Allegra M, Cerri C, Naskar S, Bony G, Zunino G, Bozzi Y, Caleo M, Cancedda L

Abstract:
Hyperpolarizing and inhibitory GABA regulates critical periods for plasticity in sensory cortices. Here we examine the role of early, depolarizing GABA in the control of plasticity mechanisms. We report that brief interference with depolarizing GABA during early development prolonged critical-period plasticity in visual cortical circuits without affecting the overall development of the visual system. The effects on plasticity were accompanied by dampened inhibitory neurotransmission, downregulation of brain-derived neurotrophic factor (BDNF) expression and reduced density of extracellular matrix perineuronal nets. Early interference with depolarizing GABA decreased perinatal BDNF signaling, and a pharmacological increase of BDNF signaling during GABA interference rescued the effects on plasticity and its regulators later in life. We conclude that depolarizing GABA exerts a long-lasting, selective modulation of plasticity of cortical circuits by a strong crosstalk with BDNF.




10/11/2014 | Nat Neurosci   IF 16.7
Dendritic channelopathies contribute to neocortical and sensory hyperexcitability in Fmr1 mice.
Zhang Y*, Bonnan A*, Bony G*, Ferezou I, Pietropaolo S, Ginger M, Sans N, Rossier J, Oostra B, Lemasson G, Frick A

Abstract:
Hypersensitivity in response to sensory stimuli and neocortical hyperexcitability are prominent features of Fragile X Syndrome (FXS) and autism spectrum disorders, but little is known about the dendritic mechanisms underlying these phenomena. We found that the primary somatosensory neocortex (S1) was hyperexcited in response to tactile sensory stimulation in Fmr1-/y mice. This correlated with neuronal and dendritic hyperexcitability of S1 pyramidal neurons, which affect all major aspects of neuronal computation, from the integration of synaptic input to the generation of action potential output. Using dendritic electrophysiological recordings, calcium imaging, pharmacology, biochemistry and a computer model, we found that this defect was, at least in part, attributable to the reduction and dysfunction of dendritic h- and BKCa channels. We pharmacologically rescued several core hyperexcitability phenomena by targeting BKCa channels. Our results provide strong evidence pointing to the utility of BKCa channel openers for the treatment of the sensory hypersensitivity aspects of FXS.




10/04/2014 | Cell Rep   IF 7.9
Polarized Expression of p75(NTR) Specifies Axons during Development and Adult Neurogenesis.
Zuccaro E, Bergami M, Vignoli B, Bony G, Pierchala BA, Santi S, Cancedda L, Canossa M

Abstract:
Newly generated neurons initiate polarizing signals that specify a single axon and multiple dendrites, a process critical for patterning neuronal circuits in vivo. Here, we report that the pan-neurotrophin receptor p75(NTR) is a polarity regulator that localizes asymmetrically in differentiating neurons in response to neurotrophins and is required for specification of the future axon. In cultured hippocampal neurons, local exposure to neurotrophins causes early accumulation of p75(NTR) into one undifferentiated neurite to specify axon fate. Moreover, knockout or knockdown of p75(NTR) results in failure to initiate an axon in newborn neurons upon cell-cycle exit in vitro and in the developing cortex, as well as during adult hippocampal neurogenesis in vivo. Hence, p75(NTR) governs neuronal polarity, determining pattern and assembly of neuronal circuits in adult hippocampus and cortical development. VIDEO ABSTRACT:




2013 | Conf Proc IEEE Eng Med Biol Soc   IF 1.1
Increased performance in genetic manipulation by modeling the dielectric properties of the rodent brain.
Szczurkowska J, dal Maschio M, Cwetsch AW, Ghezzi D, Bony G, Alabastri A, Zaccaria RP, di Fabrizio E, Ratto GM, Cancedda L

Abstract:
Genetic approaches to control DNA expression in different brain areas have provided an excellent system to characterize gene function in health and disease of animal models. With respect to others, in utero electroporation of exogenous DNA into progenitor cells committed to specific brain areas is the optimal solution in terms of simplicity and velocity. Indeed, this method entails one quick and easy surgical procedure aimed at DNA injection in the embryonic brain followed by brief exposure to a strong electric field by a bipolar electrode. Nevertheless, the technique is still lacking the necessary control and reliability in addressing the field. Moving from a theoretical model that accounts for the morphology and the dielectric properties of the embryonic brain, we developed here a set of novel and reliable experimental configurations based on the use of three electrodes for electroporation in mouse. Indeed, by means of a full 3D model of the embryonic brain and the surrounding environment, we showed that the distribution of the electric field can be finely tuned in order to target specific brain regions at a desired temporal window by proper placement of the three electrodes. In the light of this theoretical background, we manufactured a three-electrode device and performed model-guided experimental sessions. The result was an increased spatial control, extended time frames and unprecedented reliability of the genetic manipulation, with respect to the current state of the art. In particular, the outcomes of this method applied into the mouse model are reported here for the first time.




2013 | Nat Commun   IF 11.3
Non-hyperpolarizing GABAB receptor activation regulates neuronal migration and neurite growth and specification by cAMP/LKB1.
Bony G, Szczurkowska J, Tamagno I, Shelly M, Contestabile A, Cancedda L

Abstract:
gamma-Aminobutyric acid is the principal inhibitory neurotransmitter in adults, acting through ionotropic chloride-permeable GABAA receptors (GABAARs), and metabotropic GABABRs coupled to calcium or potassium channels, and cyclic AMP signalling. During early development, gamma-aminobutyric acid is the main neurotransmitter and is not hyperpolarizing, as GABAAR activation is depolarizing while GABABRs lack coupling to potassium channels. Despite extensive knowledge on GABAARs as key factors in neuronal development, the role of GABABRs remains unclear. Here we address GABABR function during rat cortical development by in utero knockdown (short interfering RNA) of GABABR in pyramidal-neuron progenitors. GABABR short interfering RNA impairs neuronal migration and axon/dendrite morphological maturation by disrupting cyclic AMP signalling. Furthermore, GABABR activation reduces cyclic AMP-dependent phosphorylation of LKB1, a kinase involved in neuronal polarization, and rescues LKB1 overexpression-induced defects in cortical development. Thus, non-hyperpolarizing activation of GABABRs during development promotes neuronal migration and morphological maturation by cyclic AMP/LKB1 signalling.




2012 | Nat Commun   IF 11.3
High-performance and site-directed in utero electroporation by a triple-electrode probe.
dal Maschio M*, Ghezzi D*, Bony G*, Alabastri A, Deidda G, Brondi M, Sato SS, Zaccaria RP, Di Fabrizio E, Ratto GM, Cancedda L

Abstract:
In utero electroporation is a powerful tool to transfect and manipulate neural-precursor cells of the rodent parietal cortex and their progeny in vivo. Although this technique can potentially target numerous brain areas, reliability of transfection in some brain regions is low or physical access is limited. Here we present a new in utero electroporation configuration based on the use of three electrodes, the relative position and polarities of which can be adjusted. The technique allows easy access and exceedingly reliable monolateral or bilateral transfection at brain locations that could only be sporadically targeted before. By improvement in the efficiency of the electrical field distribution, demonstrated here by a mathematical simulation, the multi-electrode configuration also extends the developmental timeframe for reliable in utero electroporation, allowing for the first time specific transfection of Purkinje cells in the rat cerebellum.




Abstract:
During development, Gamma-aminobutyric acidergic (GABAergic) neurons mature at early stages, long before excitatory neurons. Conversely, GABA reuptake transporters become operative later than glutamate transporters. GABA is therefore not removed efficiently from the extracellular domain and it can exert significant paracrine effects. Hence, GABA-mediated activity is a prominent source of overall neural activity in developing CNS networks, while neurons extend dendrites and axons, and establish synaptic connections. One of the unique features of GABAergic functional plasticity is that in early development, activation of GABA(A) receptors results in depolarizing (mainly excitatory) responses and Ca(2+) influx. Although there is strong evidence from several areas of the CNS that GABA plays a significant role in neurite growth not only during development but also during adult neurogenesis, surprisingly little effort has been made into putting all these observations into a common framework in an attempt to understand the general rules that regulate these basic and evolutionary well-conserved processes. In this review, we discuss the current knowledge in this important field. In order to decipher common, universal features and highlight differences between systems throughout development, we compare findings about dendritic proliferation and remodeling in different areas of the nervous system and species, and we also review recent evidence for a role in axonal elongation. In addition to early developmental aspects, we also consider the GABAergic role in dendritic growth during adult neurogenesis, extending our discussion to the roles played by GABA during dendritic proliferation in early developing networks versus adult, well established networks.