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Linking circuits to function is pivotal as brain areas may be involved in multiple circuits, and therefore a single canonical circuitry composed of specific genetically and functionally defined neuronal populations may be involved in a wide diversity of functions, and by extension in a large spectrum of pathologies.
The basal ganglia (BG) and reward systems, which are formed by a set of interconnected telencephalic and mesencephalic structures, provide a strong example of the versatility of a brain circuitry, where a wide diversity of behaviours is subserved by homologous networks, and whose dysfunction is key to numerous of psychiatric diseases (Drug addiction, Obsessive Compulsive Disorder, Attention Deficit Hyperactivity Disorder (ADHD)). The largest structure of the BG is the striatum and its ventral part, the Nucleus accumbens, is a key player in reward processes. The Striatum is composed mostly of two types of projection Striatal Projecting Neurons (SPNs), which differ in terms of gene expression and projection patterns and give rise to the direct (d) and indirect (i) pathways.
Over the years, our works has been taking advantage of the power of genetic and behavioural approaches in mice to develop tools aimed at identifying and targeting BG neuronal populations (with a particular emphasis on iSPNs and dSPNs) as their afferences in BG and reward physiopathology. Thanks to new mouse models we have analysed how BG neurons, specific pathways and genes are differentially contributing to multiple brain functions as motor control, drug addiction, goal-directed behaviours, habit and reward learning by using in vivo approaches as chemo/optogenetic, electrophysiology, calcium imaging during behavioural tasks.
Striatal projection neurons coexpressing dopamine D1 and D2 receptors modulate the motor function of D1- and D2-SPNs. Bonnavion, P., Varin, C., Fakhfouri, G., Martinez Olondo, P., De Groote, A., Cornil, A., Lorenzo Lopez, R., Pozuelo Fernandez, E., Isingrini, E., Rainer, Q. and Xu, K., Nature Neuroscience. 2024.
DOI 10.1038/s41593-024-01694-4
USP7/Maged1-mediated H2A monoubiquitination in the paraventricular thalamus: an epigenetic mechanism involved in cocaine use disorder. Cheron, J., Beccari, L., Hagué, P., Icick, R., Despontin, C., Carusone, T., Defrance, M., Bhogaraju, S., Martin-Garcia, E., Capellan, R. and Maldonado, R. Nature communications. 2023
Drug addiction: From bench to bedside.
Cheron J. & de Kerchove d’Exaerde A. Translational Psychiatry, 11: 424, 2021.
DOI 10.1038/s41398-021-01542-0
Dorsal and ventral striatal neuronal subpopulations differentially disrupt male mouse copulatory behavior.
Detraux B., Vilella A., De Groote A., Schiffmann S.N., Zoli M., de Kerchove d’Exaerde A. European Neuropsychopharmacology, 49 : 23-37, 2021.
DOI 10.1016/j.euroneuro.2021.03.007
mTOR-RhoA signalling impairments in direct striatal projection neurons induce altered behaviours and striatal physiology in mice.
Rial D., Puighermanal E., Chazalon M., Valjent E., Schiffmann S.N., de Kerchove d´Exaerde A. Biological Psychiatry, 88:945-954, 2020.
Comment from the Editor: mTOR signalling regulates striatal function, Biological Psychiatry, 88:889, 2020.
DOI 10.1016/j.biopsych.2020.05.029
It takes two to tango: Dorsal direct and indirect pathways orchestration of motor learning and behavioral flexibility.
Bonnavion P., Pozuelo Fernandez E., Varin C., & de Kerchove d’Exaerde A. Neurochemistry international, 124, 200-214, 2019.
DOI 10.1016/j.neuint.2019.01.009
Deletion of Maged1 in mice abolishes locomotor and reinforcing effets of cocaine.
De Backer J.-F., Monlezun S., Detraux B., Gazan A., Vandopdenbosch L., Cheron J., Cannazza G., Valverde S., Cantacorps L., Nassar M., Venance L., Valverde O., Faure P., Zoli M., De Backer O., Gall D., Schiffmann S.N., de Kerchove d’Exaerde A., EMBO reports, 19: e45089, 1-17, 2018.
DOI 10.15252/embr.201745089
Bidirectional Control of Reversal in a Dual Action Task by Direct and Indirect Pathway Activation in the Dorsolateral Striatum in Mice.
Laurent M., De Backer J.F., Rial D., Schiffmann S.N., de Kerchove d’Exaerde A., Frontiers in Behavioral Neuroscience, 11: 256, 2017.
DOI 10.3389/fnbeh.2017.00256
Striatopallidal Neuron NMDA Receptors Control Synaptic Connectivity, Locomotor, and Goal-Directed Behaviors.
Lambot L., Chaves Rodriguez E., Houtteman D., Li Y., Schiffmann S.N., Gall D.,de Kerchove d’Exaerde A. Journal of Neuroscience, 36(18):4976–4992, 2016.
DOI 10.1523/JNEUROSCI.2717-15.2016
FACS-array profiling identifies Ecto-5’ nucleotidase as a striatopallidal neuron-specific gene involved in striatal-dependent learning.
Ena S., De Backer J.-F., Schiffmann S.N., de Kerchove d’Exaerde A. Journal of Neuroscience, 33(20), 8794–8809, 2013.
DOI 10.1523/JNEUROSCI.2989-12.2013
Differential regulation of motor control and response to dopaminergic drugs by D1R and D2R neurons in distinct dorsal striatum subregions.
Durieux P.F., Schiffmann S.N., de Kerchove d’Exaerde A. EMBO Journal, 31, 640–653, 2012 .
DOI 10.1038/emboj.2011.400
D2R Striatopallidal neurons inhibit both locomotor and drug reward processes.
Durieux P.F., Bearzatto B, Buch T, Waisman A, Schiffmann S.N, de Kerchove d’Exaerde A. Nature Neuroscience, 12: 393-395, 2009.
DOI 10.1038/nn.2286
Lab Director: Serge Schiffmann
serge.schiffmann@ulb.be
Lab Manager: Fabienne Reisen
Phone: +32 2 555 42 30
fabienne.reisen@ulb.be
Laboratory of Neurophysiology, CP601 Bldg C, Room 3.134
ULB Campus Erasme,
808, Route de Lennik,
1070, Brussels, Belgium
Lab Director: Serge Schiffmann
serge.schiffmann@ulb.be
Lab Manager: Fabienne Reisen
Phone: +32 2 555 42 30
fabienne.reisen@ulb.be
Laboratory of Neurophysiology, CP601
Bldg C, Room 3.134
ULB Campus Erasme,
808, Route de Lennik,
1070, Brussels, Belgium
