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.
Drug addiction: From bench to bedside.
Cheron J. & de Kerchove d’Exaerde A. Translational Psychiatry, 11: 424, 2021.
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.
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.
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.
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.
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.
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.
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.
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 .
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.