Variability Within The Dopamine System

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Heterogeneity within the dopamine system becomes apparent early on in midbrain development. Dopamine neurons are derived from the sonic hedgehog positive floor plate (Abeliovich and Hammond, 2007; Blaess et al., 2011; Hayes et al., 2011; Joksimovic et al., 2009; Kittappa et al., 2007). These immature neurons migrate from the ventricular zone into the mantle guided by a complex network of interacting signalling and spatiotemporal expression of several transcription factors, (Chung et al., 2005; Di Salvio et al., 2010; Simeone, 2005; Smidt and Burbach, 2007; Smits et al., 2013). Some of this variable expression pattern also extends into adulthood: Ardbk2, Gsg2k1, Pbx1/3, Ahd2, and Dssrl1 are expressed in subsets of SNc dopamine neurons and…show more content…
The transcription factor Otx2 is prevalently detected in TH+ neurons located ventral–medial VTA neurons, and this distribution is gradually decreased in the central and dorsal–lateral VTA. It has also been shown that Otx2 is sporadically co-expressed with Girk2, while most if not all of the Otx2+ neurons are Calb+, and those located in the ventral VTA are also Ahd2+ (Di Salvio et al., 2010; Liang et al., 1996; Schein et al., 1998; Simeone et al., 2011). Despite this slight anatomical and molecular topography, the cell bodies are still largely intermingled within the midbrain nuclei (Fig 1).
One recent study attempted to deconstruct the molecular diversity of the midbrain dopamine system. They postulated the existence of several molecularly distinct dopamine neuron subtypes and used a microfluidic dynamic array to simultaneously evaluate the expression of 96 genes in single neurons (Poulin et al., 2014). Using this method identified two main clusters of neurons. They also uncovered 10 genes that appeared to be expressed uniformly in all dopamine neurons (PD linked genes: Atp13a2, Lrrk2, Park2, Park7, and Pink1. Transcription factors: Foxa1, En1/2, Lmx1b, Pitx3, and Nr4a2). Although informative, this study does have some limitations. Firstly the method used restricts the identification of novel subgroups to a combination of only 96 different genes taken from previous gene expression studies. This could have
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