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Séminaire - Eric BurguièreSpotlight on a mouse model of obsessive compulsive disorder

Abstract :

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).

Keywords: Optogenetic, Obsessive Compulsive Disorder, Animal model, Basal Ganglia

Selected publications

E. Burguière, P. Monteiro, G. Feng, AM. Graybiel. Optogenetic Stimulation of Lateral Orbitofronto-Striatal Pathway Suppresses Compulsive Behaviors. Science. (2013) Jun 7;340(6137):1243-6.

J. Jarlier*, A. Arleo*, G. Petit, J. Lefort, C. Fouquet, E. Burguière E, L. Rondi-Reig. A Navigation Analysis Tool (NAT) to assess spatial behavior in open-field and structured mazes. J Neurosci. Meth. (2013) Mar 16, 215(2):196-209.

E. Burguière, A. Arabo, F. Jarlier, C. I. De Zeeuw, L. Rondi-Reig. Role of the cerebellar cortex in conditioned goal-directed behavior. J Neurosci. (2010) Oct;30(40):13265-13271.

E. Burguière, A. Arleo, C.I. De Zeeuw, A. Berthoz, L. Rondi-Reig. Spatial navigation impairment in mice lacking LTD: a motor adaptation deficit? Nat Neurosci. (2005) Oct;8(10):1292-4.

L. Rondi-Reig and E. Burguière. Is the cerebellum ready for navigation? Prog Brain Res. (2004) ;148:199-212.

M. B. Zugaro, A. Arleo, C. Déjean, E. Burguière, M. Khamassi E.and S. I. Wiener. Apparent stability is critical in selecting landmarks: Rat anterodorsal thalamic head direction cells depend upon dynamic visual signals to select anchoring cues. Eur J Neurosci. (2004) Jul;20(2):530-6


Training and Professional Experience

2013-present Research scientist. BEBG Team, Brain and Spine Institute, Paris.

2007-2012 Post-doctorate associate. Graybiel laboratory, MIT, Cambridge, USA.

2002-2006 PhD student. LPPA, CNRS-Collège de France, Paris.

Apr.-July 2004 Research Assistant IRCCS, Santa Lucia, Roma, Italy.

Jan.-June 2000 Research Assistant University of Portsmouth, Portsmouth, England.