Differential Synaptic Remodeling by Dopamine in Direct and Indirect Striatal Projection Neurons in Pitx3-/- Mice, a Genetic Model of Parkinson's Disease

The Journal of Neuroscience : the Official Journal of the Society for Neuroscience
Luz M SuárezRosario Moratalla

Abstract

In toxin-based models of Parkinson's disease (PD), striatal projection neurons (SPNs) exhibit dendritic atrophy and spine loss concurrent with an increase in excitability. Chronic l-DOPA treatment that induces dyskinesia selectively restores spine density and excitability in indirect pathway SPNs (iSPNs), whereas spine loss and hyperexcitability persist in direct pathway SPNs (dSPNs). These alterations have only been characterized in toxin-based models of PD, raising the possibility that they are an artifact of exposure to the toxin, which may engage compensatory mechanisms independent of the PD-like pathology or due to the loss of dopaminergic afferents. To test all these, we studied the synaptic remodeling in Pitx3-/- or aphakia mice, a genetic model of PD, in which most of the dopamine neurons in the substantia nigra fail to fully differentiate and to innervate the striatum. We made 3D reconstructions of the dendritic arbor and measured excitability in identified SPNs located in dorsal striatum of BAC-Pitx3-/- mice treated with saline or l-DOPA. Both dSPNs and iSPNs from BAC-Pitx3-/- mice had shorter dendritic trees, lower spine density, and more action potentials than their counterparts from WT mice. Chronic l-DOPA treatmen...Continue Reading

Citations

May 10, 2018·Synapse·Elizabeth Monserrat Hernández-HernándezGonzalo Flores
Apr 29, 2018·Journal of Neural Transmission·M Angela CenciPer Petersson
Feb 9, 2018·Journal of Neural Transmission·Oscar Solís, Rosario Moratalla
Feb 14, 2019·Movement Disorders : Official Journal of the Movement Disorder Society·Antonio de IurePaolo Calabresi
Jan 29, 2020·Journal of Cellular Physiology·Xiaolie HeRongrong Zhu
Jul 10, 2020·Movement Disorders : Official Journal of the Movement Disorder Society·Luz M SuarezRosario Moratalla
May 13, 2020·The European Journal of Neuroscience·Ivan Castela, Ledia F Hernandez
Jun 24, 2018·Neurotoxicity Research·Noelia GranadoRosario Moratalla
Feb 28, 2019·Frontiers in Cellular Neuroscience·Steven M Graves, D James Surmeier
Apr 3, 2019·Journal of Neural Transmission·Shenyu ZhaiD James Surmeier
Sep 28, 2018·Molecular Neurobiology·José-Rubén García-MontesRosario Moratalla
Mar 19, 2020·Neurological Sciences : Official Journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology·Xi ChenWeidong Le
Apr 2, 2019·Frontiers in Neural Circuits·Yijuan Du, Steven M Graves
Dec 2, 2020·Translational Neurodegeneration·Elisabeth DinterBjörn H Falkenburger
Jun 1, 2021·Frontiers in Aging Neuroscience·Haruo NishijimaMasahiko Tomiyama
Jun 15, 2021·Journal of Parkinson's Disease·Anaıs MarieClémentine Bosch-Bouju

❮ Previous
Next ❯

Related Concepts

Related Feeds

Basal Ganglia

Basal Ganglia are a group of subcortical nuclei in the brain associated with control of voluntary motor movements, procedural and habit learning, emotion, and cognition. Here is the latest research.