Functional role of new striatopallidal or striatonigral specific genes in motor and motivational behavior
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1
Université Libre de Bruxelles, ULB Neuroscience Institute, Belgium
Basal ganglia are a set of interconnected nuclei involved in motor control and motivation. The striatum is the main input of basal ganglia and is mainly composed of medium spiny neurons, subdivided into striatopallidal (STP) and striatonigral (STN) neurons. STP and STN neurons give rise respectively to the indirect and the direct pathways of basal ganglia, with opposite effects at both motor and motivational levels. Cellular mechanisms involving these pathways in disorders such as Huntington's and Parkinson's diseases and addiction, are still poorly understood.
Our laboratory has previously identified gene expression profiles of STN and STP neurons using microarray (Ena et al., 2013). Our project consists in the study of STP or STN specific genes function in locomotor control and addiction behavior. We selected several genes according to their potential involvement in striatal pathways. Specific expression of these genes in STP or STN neurons has been validated by qPCR, in situ hybridization and/or immunofluorescence experiments. Finally, knockdown models showing specific repression in STP or STN pathway have been generated using floxed mice or shRNA interference mediated by lentivirus. Phenotypic analysis is then achieved through behavioral tests to assess the effect of gene deletion.
Résumé en Français:
Le striatum, une structure située sous le cortex du cerveau, est composé principalement de neurones épineux de taille moyenne (MSNs), subdivisés en 2 groupes de neurones : les striatopallidaux (STP) et les striatonigraux (STN). Ces deux populations neuronales sont respectivement à l’origine des voies indirecte (ou inhibitrice) et directe (ou activatrice) des noyaux de la base, présentant des effets opposés à la fois au niveau moteur et motivationnel. Le projet vise à identifier et étudier la fonction de gènes spécifiques de l’une ou l’autre de ces populations neuronales, impliquées dans différentes pathologies, telles que les maladies de Huntington et de Parkinson ou encore l’addiction.
Samenvatting in het Nederlands:
Het striatum, een structuur die zich in de hersenen onder de hersenschors bevindt is hoofdzakelijk samengesteld uit middelgrote stekelige neuronen (MSNs), onderverdeeld in 2 groepen: de striatopaliden (STP) en de striatonigralen (STN). Deze twee neuronenfamilies liggen aan de bron van respectievelijk de indirecte (of afremmende) en de directe (activerende) doorgangen van de knooppunten van basale cellen, met tegengestelde effecten enerzijds op motorisch of motivationeel niveau. Het project is gericht op het identificeren en bestuderen van de werking van de genen eigen aan de ene of de andere neuronenfamilie, betrokken bij verschillende ziekten, zoals de ziekte van Huntington, de ziekte van Parkinson of ook verslaving.
Acknowledgements
D.K.. was supported by a Research Fellow grant of the Fonds National de la Recherche Scientifique (FRS-FNRS) (Belgium).
References
Ena, S. L., De Backer, J. F., Schiffmann, S. N., de Kerchove d'Exaerde, A. (2013). FACS array profiling identifies Ecto-5' nucleotidase as a striatopallidal neuron-specific gene involved in striatal-dependent learning. J Neurosci 33, 8794-809, doi :10.1523/JNEUROSCI.2989-12.2013
Keywords:
Striatum,
striatonigral pathway,
striatopallidal pathway,
cell-type-specific gene,
knockdown model
Conference:
6th Belgian Brain Congress, MONS, Belgium, 8 Oct - 8 Oct, 2016.
Presentation Type:
Poster Presentation
Topic:
Brain and brain diseases: between heredity and environment
Citation:
Karadurmus
D,
Ena
SL,
De Kerchove D'Exaerde
A and
Schiffmann
SN
(2016). Functional role of new striatopallidal or striatonigral specific genes in motor and motivational behavior.
Conference Abstract:
6th Belgian Brain Congress.
doi: 10.3389/conf.fnagi.2016.03.00049
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Received:
29 Jun 2016;
Published Online:
07 Jul 2016.
*
Correspondence:
Miss. Deniz Karadurmus, Université Libre de Bruxelles, ULB Neuroscience Institute, Brussels, Belgium, denizkaradurmus@hotmail.com