Functional Interplay between Dopaminergic and Serotonergic Neuronal Systems during Development and Adulthood

Abstract

The complex integration of neurotransmitter signals in the nervous system contributes to the shaping of behavioral and emotional constitutions throughout development. Imbalance among these signals may result in pathological behaviors and psychiatric illnesses. Therefore, a better understanding of the interplay between neurotransmitter systems holds potential to facilitate therapeutic development. Of particular clinical interest are the dopaminergic and serotonergic systems, as both modulate a broad array of behaviors and emotions and have been implicated in a wide range of affective disorders. Here we review evidence speaking to an interaction between the dopaminergic and serotonergic neuronal systems across development. We highlight data stemming from developmental, functional, and clinical studies, reflecting the importance of this transmonoaminergic interplay.

Dopamine Modulates Serotonin Innervation in the Drosophila Brain

“…Whereas the AL is mainly innervated by 5-HT neurons and only faintly at the outer rim by TH immunoreactive neurons, the PB appears to be innervated exclusively be TH-positive neurons, but not by 5-HT. These innervations resemble to some extend the situation in the vertebrate brain where projections of DA-producing neurons are for the most part accompanied by 5-HT producing neurons (Niederkofler et al, 2015 ).…”

“…Out of these ~90 5-HT producing neurons about 80 neurons can be targeted by TrH-Gal4 (Sitaraman et al, 2008 ; Cassar et al, 2015 ) that however drives ectopic expression in nearly 170 non-serotoninergic neurons (Figure 1B ; see also Pooryasin and Fiala, 2015 ). Similar to vertebrates, where neuropils that are innervated by DA producing neurons are also innervated by 5-HT neurons (Niederkofler et al, 2015 ), with the exceptions of the antennal lobes (AL) that are innervated by 5-HT producing neurons but only sparsely at the outer rim by DA neurons (Figures 2A1–3 ) and the protocerebral bridge (PB) that is innervated by DA neurons but not by 5-HT producing neurons (Figure 2E1 ), both aminergic systems innervate the same target regions, but differ in their density on local innervation patterns. At the anterior side, the serotoninergic system can be subdivided in a medial (AMP) and a dorsomedial (ADMP—anterior dorso medial protocerebrum) cluster and a small group of neurons positioned in the anterior lateral protocerebrum (ALP) and a large of group of neurons positioned between the OL and the CNS in the lateral protocerebrum (LP).…”

“…In vertebrate models of PD, degeneration of DA neurons leads to modifications in 5-HT neurons (Zhou et al, 1991 ; Rylander et al, 2010 ; Zeng et al, 2010 ; Niederkofler et al, 2015 ). To determine whether the same holds true for Drosophila , we analyzed the innervation pattern of 5-HT neurons onto their target region in the vertical MB lobes.…”

“…Here we investigated the effects of altered DA signaling on the 5-HT circuitry in the CNS of adult fruit flies. As in vertebrates (Niederkofler et al, 2015 ), the DA and 5-HT neurons of Drosophila send their projections to many brain areas. Most neuropils that are innervated by TH-immunoreactive neurons are also innervated by 5-HT-producing neurons.…”

Identification of Serotonergic Neuronal Modules that Affect Aggressive Behavior

“…Such a pattern suggests reciprocal circuitry, wherein midbrain dopaminergic neurons send projections to the rostral serotonergic system and vice versa (Niederkofler et al, 2015). Sources of dopaminergic innervation of the Drd/Pet1 subtypes may include the rostral DR in addition to the SNc and midbrain VTA.…”