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Thomas STEFANELLI





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Cursus:
PhD - University of Geneva - C. Lüscher lab (2017)
MS - University of Geneva - D. Muller lab - (2014)
BS - University of Geneva (2012)

Expertise: #Optogenetics, #Chemogenetics, #Behavior, #Engrams, #Memory, #NeuralCircuits



www.stefanellithomas.org



4 publication(s) depuis Mars 2016:


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


06/02/2018 | Cell Rep   IF 8
Homeostatic Plasticity in the Hippocampus Facilitates Memory Extinction.
Mendez P, Stefanelli T, Flores CE, Muller D, Luscher C

Abstract:
Correlated activity in the hippocampus drives synaptic plasticity that is necessary for the recruitment of neuronal ensembles underlying fear memory. Sustained neural activity, on the other hand, may trigger homeostatic adaptations. However, whether homeostatic plasticity affects memory function remains unknown. Here, we use optogenetics to induce cell autonomous homeostatic plasticity in CA1 pyramidal neurons and granule cells of the hippocampus. High-frequency spike trains applied for 10 min decreased the number of excitatory spine synapses and increased the number of inhibitory shaft synapses. This activity stopped dendritic spine formation via L-type voltage-dependent calcium channel activity and protein synthesis. Applied selectively to the ensemble of granule cells encoding a contextual fear memory, the spike trains impaired memory recall and facilitated extinction. Our results indicate that homeostatic plasticity triggered by optogenetic neuronal firing alters the balance between excitation and inhibition in favor of memory extinction.




01/07/2017 | Cereb Cortex   IF 6.3
Palmitoylation of cdc42 Promotes Spine Stabilization and Rescues Spine Density Deficit in a Mouse Model of 22q11.2 Deletion Syndrome.
Moutin E, Nikonenko I, Stefanelli T, Wirth A, Ponimaskin E, De Roo M, Muller D

Abstract:
22q11.2 deletion syndrome (22q11DS) is associated with learning and cognitive dysfunctions and a high risk of developing schizophrenia. It has become increasingly clear that dendritic spine plasticity is tightly linked to cognition. Thus, understanding how genes involved in cognitive disorders affect synaptic networks is a major challenge of modern biology. Several studies have pointed to a spine density deficit in 22q11DS transgenic mice models. Using the LgDel mouse model, we first quantified spine deficit at different stages using electron microscopy. Next we performed repetitive confocal imaging over several days on hippocampal organotypic cultures of LgDel mice. We show no imbalanced ratio between daily spine formation and spine elimination, but a decreased spine life expectancy. We corrected this impaired spine stabilization process by overexpressing ZDHHC8 palmitoyltransferase, whose gene belongs to the LgDel microdeletion. Overexpression of one of its substrates, the cdc42 brain-specific variant, under a constitutively active form (cdc42-palm-CA) led to the same result. Finally, we could rescue spine density in vivo, in adult LgDel mice, by injecting pups with a vector expressing cdc42-palm-CA. This study reveals a new role of ZDHHC8-cdc42-palm molecular pathway in postsynaptic structural plasticity and provides new evidence in favor of the dysconnectivity hypothesis for schizophrenia.




05/2017 | nat methods
Temporally precise labeling and control of neuromodulatory circuits in the mammalian brain.
Lee D, Creed M, Jung K, Stefanelli T, Wendler DJ, Oh WC, Mignocchi NL, Luscher C, Kwon HB

Abstract:
Few tools exist to visualize and manipulate neurons that are targets of neuromodulators. We present iTango, a light- and ligand-gated gene expression system based on a light-inducible split tobacco etch virus protease. Cells expressing the iTango system exhibit increased expression of a marker gene in the presence of dopamine and blue-light exposure, both in vitro and in vivo. We demonstrated the iTango system in a behaviorally relevant context, by inducing expression of optogenetic tools in neurons under dopaminergic control during a behavior of interest. We thereby gained optogenetic control of these behaviorally relevant neurons. We applied the iTango system to decipher the roles of two classes of dopaminergic neurons in the mouse nucleus accumbens in a sensitized locomotor response to cocaine. Thus, the iTango platform allows for control of neuromodulatory circuits in a genetically and functionally defined manner with spatial and temporal precision.




02/03/2016 | Neuron   IF 14.3
Hippocampal Somatostatin Interneurons Control the Size of Neuronal Memory Ensembles.
Stefanelli T, Bertollini C, Luscher C, Muller D, Mendez P

Abstract:
Hippocampal neurons activated during encoding drive the recall of contextual fear memory. Little is known about how such ensembles emerge during acquisition and eventually form the cellular engram. Manipulating the activity of granule cells (GCs) of the dentate gyrus (DG), we reveal a mechanism of lateral inhibition that modulates the size of the cellular engram. GCs engage somatostatin-positive interneurons that inhibit the dendrites of surrounding GCs. Our findings reveal a microcircuit within the DG that controls the size of the cellular engram and the stability of contextual fear memory.