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Dopamine regulates spine density in striatal projection neurons in a concentration-dependent manner.

AuthorsAlberquilla, S.; Gonzalez-Granillo, A; Martín, E. D.; Moratalla, Rosario
Spiny projection neuron
Parkinson's disease
Synaptic plasticity
Issue Date2020
PublisherAcademic Press
CitationNeurobiology of Disease 134: 104666 (2020)
AbstractDopaminergic afferents innervate spiny projection neurons (SPNs) in the striatum, maintaining basal gangliaactivity. The loss of striatal innervation is the hallmark of Parkinson's disease (PD), which is characterized bydopaminergic denervation. A lack of dopamine in the dorsal striatum induces plasticity changes in SPNs.However, PD-associated denervation is progressive, and how plasticity is modified in partially innervated areasis poorly understood. The most studied models of PD are based on the use of neurotoxins that induce an almostcomplete striatal denervation. To investigate the impact of partial dopamine (DA) innervation in striatal plas-ticity, we use a genetic model of PD, Aphakia (Ak) mice, whose striatum presents an increasing dorso-ventralgradient of dopamine innervation. We studied SPNs in three different areas (dorsal, middle and ventral, withlow, moderate and high innervation by tyrosine hydroxylase TH-positive axons, respectively) using fast scancyclic voltammetry, microiontophoresis, immunohistochemistry and patch clamp techniques. Our data show anincreasing dorso-ventral gradient of extracellular DA levels, overlapping with the gradient of TH innervation.Interestingly, spine loss in both direct (d-SPN) and indirect SPNs (i-SPN) decreases from dorsal to ventral in theparkinsonian striatum of Ak mice, following the decrease in DA levels. However, their dendritic trees and thenumber of nodes are only reduced in the poorly innervated dorsal areas and remain unaltered in moderate andhighly innervated areas. Thefiring rate of direct SPNs does not change in either moderate or highly innervatedareas, but increases in poorly innervated areas. In contrast, action potential frequency of indirect SPNs does notchange along the dorso-ventral innervation gradient. Ourfindings indicate that spine density in d-SPNs and i-SPNs varies in a dopamine concentration-dependent manner, indicating that both d- and i-SPN are similarlyinnervated by DA.
Publisher version (URL)http://dx.doi.org/10.1016/j.nbd.2019.104666
Identifiersdoi: 10.1016/j.nbd.2019.104666
issn: 1095-953X
Appears in Collections:(IC) Artículos
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