Alban de Kerchove d’Exaerde

Lab of Neurophysiology
ULB Neuroscience Institute
Université Libre de Bruxelles (ULB)

Invited by Philippe Isope

Summary

Motivational processes are under the critical influence of the ventral part of basal ganglia, comprising several interconnected nuclei (as striatum, globus pallidus and ventral tegmental area (VTA)). Addictive drugs increase extracellular DA levels in the ventral striatum, Nucleus Accumbens (NAc), and share this ability despite varied pharmacological properties and mechanisms of action. A major goal in the field of drug addiction has been to uncover the molecular mechanisms underlying addiction-associated neuroadaptations. It has been hypothesized that one such mechanism is the regulation of gene expression7, and there have been numerous studies that have documented altered expression of genes in the NAc. We discovered that Maged1 (Melanoma antigen genes d1) has a mandatory role in behaviours related to drug addiction in BG. Mice lacking Maged1 are insensitive to the behavioural effects of cocaine as assessed by locomotor sensitization, conditioned place preference (CPP), and drug self-administration. Electrophysiological experiments in brain slices and conditional KO mice demonstrated that Maged1 is critical for cortico-accumbal neurotransmission. Further, expression of Maged1 in the prefrontal cortex and amygdala, but not in dopaminergic or striatal neurons, is required for cocaine-induced extracellular DA release in the NAc as well as cocaine-mediated behavioural sensitization and acute cocaine effect respectively. This work identifies Maged1 as a critical molecule involved in cellular processes in BG and behavioural models of addiction.

Bibliography

L.  Lambot, E. Chaves Rodriguez, D. Houtteman, Y. Li, S.N. Schiffmann, D. Gall and A. de Kerchove d’Exaerde (2016). Striatopallidal Neuron NMDA Receptors Control Synaptic Connectivity, Locomotor, and Goal-Directed Behaviors. J. Neurosci.  36, 4976-4992.

A.C. Meirsman, A. Robé, A. de Kerchove d’Exaerde and B.L. Kiefer (2016). GPR88 in A2AR neurons enhances anxiety-like behaviors. eNeuro 3, pii: ENEURO.0202-16.2016. 

A.   Natsubori,  I. Tsutsui-Kimura, H. Nishida, Y. Bouchekioua, H. Sekiya, M. Uchigashima, M. Watanabe, A.  de Kerchove d'Exaerde, M. Mimura, N. Takata N,  and  K.F. Tanaka (2017). Ventrolateral striatal medium spiny neurons positively regulate fond-incentive, goal-directed behavior independently of D1 and D2 selectivity.  J. Neurosci.  37, 2723-2733.

 A.C. Meirsman, A. de Kerchove d’Exaerde, B.L. Kiefer  and A.M. Ouagazzal (2017). GPR88 in A2Areceptor-expressing neurons modulates locomotor response to dopamine agonists but not sensorimotor gating.  Eur. J. Neurosci.  46, 2026-2034.

I. Tsutsui-Kimura, A. Natsubori, M. Mori, K. Kobayashi, M. R.  Drew,  A. de Kerchove d’Exaerde, M. Mimura and  K.  F. Tanaka (2017). Distinct roles of ventromedial versus ventrolateral striatal spiny neurons in reward-oriented behavior. Curr. Biol. 27, 3042-3048.

Y. Oishi, Q. Xu, L. Wang, B.-J. Zhang, K. Takahashi, Y. Takata, Y.-J. Luo, Y. Cherasse, S. N. Schiffmann, A. de Kerchove d’Exaerde, Y. Urade, W.-M. Qu, Z.-L. Huang and M. Lazarus (2017). Slow-wave sleep is controlled by a subset of nucleus accumbens neurons in mice. Nat. Comm. 8 , 734.

X.-S. Yuan, L. Wang, H. Dong, W.-M. Qu, S.-R. Yang, Y. Cherasse, M. Lazarus, S. N. Schiffmann,
A. de Kerchove d’Exaerde, R.-X. Li, Z.-L. Huang (2017). Striatal adenosine A2A receptor neurons control active-period sleep via parvalbumin neurons in external globus pallidus. eLife 6, e29055.

M. Laurent, J.-F. De Backer, D. Rial, S. N. Schiffmann and A. de Kerchove d’Exaerde (2017).  Bidirectional control of reversal in a dual action task by direct and indirect pathway activation in the dorsolateral striatum in mice. Front. Behav. Neurosci. 11, 256.

J.-F. De Backer, S. Monlezun, B. Detraux, A. Gazan,  L. Vanopdenbosch, J. Cheron, G. Cannazza, S. Valverde, L. Catacorps, M. Nassar, L. Venance, O. Valverde, P. Faure, M. Zoli, O. De Backer, S. N. Schiffmann, D. Gall and A. de Kerchove d'Exaerde (2018). Deletion of Maged1 in mice abolishes locomotor and reinforcing effects of cocaine. EMBO Rep. 19, e45089

H. Xu, S. Perez, A. Cornil, B. Detraux, I. Prokin, Y. Cui, B. Degos, H. Berry, A. de Kerchove d’Exaerde and L. Venance (2018).  Dopamine-endocannabinoid interactions mediate spike-timing dependent potentiation in the striatum. Nat. Comm. 9, 4118.

P. Bonnavion, E. Pozuelo Fernandez, Christophe Varin and A. de Kerchove d’Exaerde (2019). It takes two to tango: Dorsal direct and indirect pathway orchestration of motor learning and behavioral flexibility. Neurochem. Int. 124, 200-214.

A.   C. Meirsman, S.B. Hamida, E. Clarke, A. de Kerchove d'Exaerde, E. Darcq, and B.L. Kieffer (2019). GPR88 in D1R- and D2R-type medium spiny neurons differentially regulates affective and motor behaviors.  eNeuro, in press.

D. Karadurmus, D. Rial, J.F. De Backer, A. de Kerchove d’Exaerde* and S.N. Schiffmann*(2019).  GPRIN_3 controls neuronal excitability, morphology and striatal-dependent behaviors in the indirect pathway of the striatum. J. Neurosci. 39, 7513-7528.  * Both authors contributed equally to this work

D. Rial, E. Puighermal, E. Valjent, S.N .Schiffmann and A de Kerchove d’Exaerde (2019). mTOR-RhoA signalling impairments in direct striatal projection neurons induce altered behaviours and striatal physiology in mice. BioRxiv.  doi: doi.org/10.1101/858712

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