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Séminaire impromptu - Camilla BelloneSocial motivation deficits in ASDs : dissecting the role of reward system

Abstract :

 Postnatal periods of development are characterized by rapid changes in neuronal networks, providing critical periods in which environmental experience can lead to long-term changes in brain and behavior.
During this period, the brain is highly malleable and changes in experience can affect synaptic maturation, circuit refinement and can also induce persistent alterations in behaviors.

In mouse animal model, combining electrophysiological techniques with molecular approaches and behavioral paradigms, we investigate how the reward system during the postnatal development encodes experience and how defect in these processes may lead to neurodevelopmental disorders such as Autism Spectrum Disorders (ASDs) or Schizophrenia.
The mesocorticolimbic system processes natural rewards and originates in the ventral tegmental area (VTA) where dopaminergic (DA) neurons primarily project to the prefrontal cortex (PFC) and nucleus accumbens (NAc). DA neurons can be activated by primary rewards and by environmental stimuli associated with reward experience. How can DA neurons encode such reward value? And similarly, how do animals learn about stimuli associated with reward experiences and respond appropriately to them?

Excitatory inputs onto the DA neurons provide information on reward experience and specific forms of synaptic plasticity at these inputs could underlie reward learning associated with reward experiences. Altered excitatory transmission during the postnatal development may therefore lead to changes in reward perception and as consequence be at the basis of several neurodevelopmental disorders.

Selected publications

Gabrielle Pouchelon, Frédéric Gambino, Camilla Bellone, Christian Lüscher, Anthony Holtmaat, Denis Jabaudon. Rewiring of distinct thalamocortical inputs instructs the modality-specific identity of postsynaptic L4 neurons. Nature. 2014 May 14. doi: 10.1038/nature13390 [Pubmed]
Eoin C. O’Connor*, Sebastiano Bariselli* and Camilla Bellone Synaptic Basis of Social Dysfunction: A focus on Postsynaptic Proteins Linking Group-I mGluRs with AMPARs and NMDARs Eur J Neurosci. 2014 Apr;39(7):1114-29 [Pubmed]
Yuan T, Mameli M, O’ Connor E.C, Dey P.N, Verpelli C, Sala C, Perez-Otano I, Lüscher C. and Bellone C. Expression of cocaine-evoked synaptic plasticity by GluN3A-containing NMDA receptors. Neuron, 2013 Nov 20;80(4):1025-38. [Pubmed]
Tifei Yuan and Camilla Bellone Glutamatergic receptors at developing synapses: the role of GluN3A-containing NMDARs and GluA2-lacking AMPARs. Eur. J Pharmacol. 2013 Jul 17. ejphar.2013.04.056. [Epub ahead of print]. [Pubmed]
Pierre Paoletti, Camilla Bellone and Qiang Zhou NMDA receptor subunit diversity: impact on receptor properties, synaptic plasticity and disease Nat. Rev. Neurosci. 2013 Jun;14(6):383-400 [Pubmed]