Serotonin Receptors Expressed in Drosophila Mushroom Bodies Differentially Modulate Larval Locomotion

Abstract

Drosophila melanogaster has been successfully used as a simple model to study the cellular and molecular mechanisms underlying behaviors, including the generation of motor programs. Thus, it has been shown that, as in vertebrates, CNS biogenic amines (BA) including serotonin (5HT) participate in motor control in Drosophila. Several evidence show that BA systems innervate an important association area in the insect brain previously associated to the planning and/or execution of motor programs, the Mushroom Bodies (MB). The main objective of this work is to evaluate the contribution of 5HT and its receptors expressed in MB to motor behavior in fly larva. Locomotion was evaluated using an automated tracking system, in Drosophila larvae (3rd-instar) exposed to drugs that affect the serotonergic neuronal transmission: alpha-methyl-L-dopa, MDMA and fluoxetine. In addition, animals expressing mutations in the 5HT biosynthetic enzymes or in any of the previously identified receptors for this amine (5HT1AR, 5HT1BR, 5HT2R and 5HT7R) were evaluated in their locomotion. Finally, RNAi directed to the Drosophila 5HT receptor transcripts were expressed in MB and the effect of this manipulation on motor behavior was assessed. Data obtained in the mutants and in animals exposed to the serotonergic drugs, suggest that 5HT systems are important regulators of motor programs in fly larvae. Studies carried out in animals pan-neuronally expressing the RNAi for each of the serotonergic receptors, support this idea and further suggest that CNS 5HT pathways play a role in motor control. Moreover, animals expressing an RNAi for 5HT1BR, 5HT2R and 5HT7R in MB show increased motor behavior, while no effect is observed when the RNAi for 5HT1AR is expressed in this region. Thus, our data suggest that CNS 5HT systems are involved in motor control, and that 5HT receptors expressed in MB differentially modulate motor programs in fly larvae.

Cell-Type-Specific Transcriptome Analysis in the Drosophila Mushroom Body Reveals Memory-Related Changes in Gene Expression

“…We were also able to identify the neurotransmitter receptors dominant in each of these cell types (Figure 4A). While we confirmed that KCs express DopR, DopR2, OAMB, and 5-HT1A and 1B receptors (Han et al, 1998; Han et al, 1996; Qin et al, 2012; Silva et al, 2014; Yuan et al, 2006), we discovered that these receptors are also expressed in MBONs, but at lower levels than in the KCs (see also Figure S5). This indicates that both the KCs and MBONs have the ability to respond to the dopamine signal (carrying information about punishment or reward) innervating each compartment of the MB lobes.…”

Serotonin in Animal Cognition and Behavior

“…Animals expressing RNAi for d5-HT 1B , d5-HT 2 or d5-HT 7 , but not d5-HT 1A in MBs showed increased motor behavior. Thus, all three d5-HTRs expressed in MBs decrease locomotor activity in fly larvae, although the activation of d5-HT 1B in other CNS regions may counteract its own action in the MBs [81]. Similarly, it has been reported in the leech that 5-HT activates the locomotor network at the nerve cord level, but inhibits locomotion at the head brain level [61].…”

Timing of locomotor recovery modulated by thewhitegene inDrosophila

“…CNS-located serotonin neurons provide a tissue basis for additional roles for White other than in controlling eye color in pigment cells. These neurons release serotonin (5HT), which acts as a neuromodulator involved in locomotor behavior, circadian entrainment and place memory (YUAN et al 2005;SITARAMAN et al 2008;NALL and SEHGAL 2014;OKUSAWA et al 2014;SILVA et al 2014). Recovery from anoxia includes the restoration of 5HT vesicular stores that would be excessively released during anoxic coma (HANSEN 1985).…”