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Spotlight on a mouse model of obsessive compulsive disorder| old_uid | 12789 |
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| title | Spotlight on a mouse model of obsessive compulsive disorder |
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| start_date | 2013/09/20 |
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| schedule | 11h30 |
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| online | no |
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| details | Une invitation d’Etienne Coutureau, CNRS UMR 5287 - INCIA, Team leader: Neurobiologie des fonctions exécutives. |
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| summary | It has been shown these last years that optogenetic tool, that uses a combination of optics and genetics technics to control neuronal activity with light on behaving animals, allow to establish causal relationship between brain activity and normal or pathological behaviors (Tye KM, Deisseroth K. Nat Rev Neurosci. 2012 Mar 20;13(4):251-66). In combination with animal model of neuropsychiatric disorder, optogenetic could help to identify deficient circuitry in numerous pathologies by exploring functional connectivity, with a specificity never reached before, while observing behavioral and/or physiological correlates.
To illustrate the promising potential of these tools for the understanding of psychiatric diseases, we will present our recent study where we used optogenetic to block abnormal repetitive behavior in a mutant mouse model of obsessive compulsive disorder, the SAPAP3-KO mice (Burguière E et al. Science. 2013 Jun 7;340(6137):1243-6). Using a delay-conditioning task we showed that these mutant mice had a deficit in response inhibition that lead to repetitive behaviour.
With electrophysiological recording we also observed that mutants had hyperactive striatal projection neurons. We then used optogenetic to stimulate the orbitofrontal-striatal pathway in the SAPAP3-KO mice, a circuitry known to play an important role in response inhibition and to be dysfunctional in compulsive behaviors.
We observed that optogenetic stimulations, through their effect on striatal interneurons, could restore normal striatal activity and, importantly, could restore the behavioral response inhibition and alleviate the compulsive behavior. These findings raise promising potential for the design of targeted deep brain stimulation therapy for psychiatric disorders and for a better understanding of therapeutical mechanism underlying stimulation protocols already used in clinic (Mallet L et al., N Engl J Med. 2008 Nov 13;359(20):2121-34). |
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| responsibles | Deris |
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