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Eisuke KOYA"The identification and synaptic characterization of nucleus accumbens neuronal ensembles that mediate context-specific sensitization"

Abstract :

Learned associations about cocaine effects and its administration context play an important role in the development of cocaine addiction.
I utilize the context-specific sensitization to cocaine procedure to study how these learned associations modulate cocaine-induced locomotor activity and nucleus accumbens neuronal activity. Rats express a sensitized response to cocaine only when test injections are administered in the cocaine-paired environment. We found that only 2-3% of nucleus accumbens neurons are activated enough to induce Fos protein expression following the test injection. We asked whether this minority of responsive neurons were actually 'responsible' for mediating these learned associations. And if so, what synaptic alterations could underlie the altered responsiveness of these neurons?

In my talk I will discuss how I developed and utilized the Daun02 inactivation procedure in c-fos-lacZ transgenic rats that selectively inactivates Fos-expressing neurons that were previously activated by cocaine exposure in the drug-paired environment. From this we hypothesize that the learned associations underlying context-specific sensitization are mediated by sparsely distributed neuronal ensembles in the nucleus accumbens (Koya et al., 2009 Nature Neuroscience). I will also discuss how I utilized c-fos-GFP transgenic mice that express GFP in Fos-expressing activated neurons, to show that the neurons that comprise these behaviorally activated ensemble have unique alterations in synaptic physiology.

Selected publications

J.M. Bossert, A.L. Stern, F.R.M. Theberge, C. Cifani, E. Koya, B.T. Hope, Y.Shaham. Ventral medial prefrontal cortex neuronal ensembles mediate context-induced relapse to heroin seeking. Nature Neuroscience. 2011 In press.
E. Koya, S.A. Golden, B.K. Harvey, D.H. Guez-Barber, A. Berkow, D.E. Simmons, J.M. Bossert, S.G. Nair, J.L. Uejima, M.T. Marin, T.B. Mitchell, D. Farquhar, S.C. Ghosh, B.J. Mattson, B.T. Hope. Targeted disruption of sparsely distributed cocaine-activated accumbens neurons prevents context-specific psychomotor sensitization. Nature Neuroscience. 2009 Aug;12(8):1069-73.
E. Koya, J.M. Bossert, J.L. Uejima, K. Wihbey, B.T. Hope, Y. Shaham. Role of ventral medial prefrontal cortex in incubation of cocaine craving. Neuropharmacology. 2009;56 Suppl 1:177-85.
L. Lu*, E. Koya*, H. Zhen, B.T. Hope, Y.Shaham. Role of ERK in cocaine addiction.Trends in Neurosciences. 2006 Dec;29(12):695-703.

Véronique Deroche Gamonet du Neurocentre Magendie