Expression of a Novel D4 Dopamine Receptor in the Lamprey Brain. Evolutionary Considerations about Dopamine Receptors

Abstract

Numerous data reported in lampreys, which belong to the phylogenetically oldest branch of vertebrates, show that the dopaminergic system was already well developed at the dawn of vertebrate evolution. The expression of dopamine in the lamprey brain is well conserved when compared to other vertebrates, and this is also true for the D2 receptor. Additionally, the key role of dopamine in the striatum, modulating the excitability in the direct and indirect pathways through the D1 and D2 receptors, has also been recently reported in these animals. The moment of divergence regarding the two whole genome duplications occurred in vertebrates suggests that additional receptors, apart from the D1 and D2 previously reported, could be present in lampreys. We used in situ hybridization to characterize the expression of a novel dopamine receptor, which we have identified as a D4 receptor according to the phylogenetic analysis. The D4 receptor shows in the sea lamprey a more restricted expression pattern than the D2 subtype, as reported in mammals. Its main expression areas are the striatum, lateral and ventral pallial sectors, several hypothalamic regions, habenula, and mesencephalic and rhombencephalic motoneurons. Some expression areas are well conserved through vertebrate evolution, as is the case of the striatum or the habenula, but the controversies regarding the D4 receptor expression in other vertebrates hampers for a complete comparison, especially in rhombencephalic regions. Our results further support that the dopaminergic system in vertebrates is well conserved and suggest that at least some functions of the D4 receptor were already present before the divergence of lampreys.

Evolutionarily conserved organization of the dopaminergic system in lamprey: SNc/VTA afferent and efferent connectivity and D2 receptor expression

“…Some clear differences exist, as in the case of the medial olfactory bulb, the medial preoptic nucleus, and the interpeduncular nucleus, which are devoid of D1 receptor expression, but where D2 receptor expression is abundant. Conversely, some regions where no D2 expression was detected show D1 receptor expression, as in the oculomotor nucleus and the M5 nucleus (present results; Pombal et al, ; Pérez‐Fernández, ).…”

“…The D1 and D2 receptors share many common areas in the lamprey brain (Pérez‐Fernández, ), although, as in the striatum, they most likely are expressed in separate cell populations (Ericsson et al, ), and the D2 receptor shows in general a more abundant expression. Some clear differences exist, as in the case of the medial olfactory bulb, the medial preoptic nucleus, and the interpeduncular nucleus, which are devoid of D1 receptor expression, but where D2 receptor expression is abundant.…”

“…The cDNA encoding the dopamine D2 receptor in the lamprey was recently identified, and the deduced protein sequence showed a close phylogenetic relationship with other vertebrate D2 receptors (Robertson et al, ). The presence of an additional receptor within the D2 class, identified as a D4 receptor (Pérez‐Fernández, ), and the distribution of dopamine in the lamprey brain, also support the possibility that the dopaminergic system is well developed in the lamprey (Pierre et al, ; Pombal et al, ; Abalo et al, ; Barreiro‐Iglesias et al, ). Apart from D2 receptor expression in striatal projection neurons, the dopaminergic input from the SNc/VTA to other areas containing the D2 receptor has not been reported.…”

“…Dopamine acts through two classes of receptors, D1 and D2, belonging to class I (Rhodopsin‐like receptors) G‐protein–coupled receptors (GPCRs) (Callier et al, ). The presence of D1 and D2 receptors in lamprey, with similar actions in the basal ganglia as in mammals, suggests that dopamine receptors are highly conserved (Pombal et al, ; Robertson et al, ; Ericsson et al, ; Pérez‐Fernández, ; Stephenson‐Jones et al, ). The cDNA encoding the dopamine D2 receptor in the lamprey was recently identified, and the deduced protein sequence showed a close phylogenetic relationship with other vertebrate D2 receptors (Robertson et al, ).…”

Cloning of the GABAB Receptor Subunits B1 and B2 and their Expression in the Central Nervous System of the Adult Sea Lamprey

“…Positive in situ signal in sea lamprey brain sections had a granular appearance probably due to low expression of these mRNAs in each single cell of the sea lamprey. Previous studies looking at the expression of different neurotransmitter receptors in lampreys have shown that the in situ hybridization signals appeared as a dotted labeling in sections of the CNS: serotonin receptor 1A (Cornide-Petronio et al, 2013, 2014), dopamine receptor D2 (Robertson et al, 2012; Fernández-López et al, 2015), and dopamine receptor D4 (Pérez-Fernández et al, 2016); suggesting that low expression levels are a common feature of different metabotropic neurotransmitter receptors.…”