Serotonin receptor 5-HT7 in Drosophila mushroom body neurons mediates larval appetitive olfactory learning

Archan Ganguly,Daewoo Lee,Jeevisha Bajaj,Cheng Qi

doi:10.1038/s41598-020-77910-5

Archan Ganguly, Daewoo Lee + Show 2 more

Open Access

https://doi.org/10.1038/s41598-020-77910-5

Copy DOI

Abstract

Serotonin (5-HT) and dopamine are critical neuromodulators known to regulate a range of behaviors in invertebrates and mammals, such as learning and memory. Effects of both serotonin and dopamine are mediated largely through their downstream G-protein coupled receptors through cAMP-PKA signaling. While the role of dopamine in olfactory learning in Drosophila is well described, the function of serotonin and its downstream receptors on Drosophila olfactory learning remain largely unexplored. In this study we show that the output of serotonergic neurons, possibly through points of synaptic contacts on the mushroom body (MB), is essential for training during olfactory associative learning in Drosophila larvae. Additionally, we demonstrate that the regulation of olfactory associative learning by serotonin is mediated by its downstream receptor (d5-HT7) in a cAMP-dependent manner. We show that d5-HT7 expression specifically in the MB, an anatomical structure essential for olfactory learning in Drosophila, is critical for olfactory associative learning. Importantly our work shows that spatio-temporal restriction of d5-HT7 expression to the MB is sufficient to rescue olfactory learning deficits in a d5-HT7 null larvae. In summary, our results establish a critical, and previously unknown, role of d5-HT7 in olfactory learning.

Highlights

The reconstituted splitGFP signals are mainly observed in the upper vertical lobe (UVL) compartment and the shaft (SHA) compartment of the medial lobe (Fig. 1A). Both these regions of the mushroom body have been implicated in Drosophila larval learning[5,15]. This innervation pattern is similar to that seen for the MBIN-e2 neuron reported by Eichler et al.[11], which is negative for neurotransmitters dopamine or octopamine
Our results clearly demonstrate that points of synaptic contacts exist between serotonergic neurons and the mushroom body of Drosophila larvae, with innervation patterns unlike any dopaminergic or octopaminergic neuron
In this study we demonstrate that the output of serotonergic neurons is essential for olfactory appetitive learning and demonstrate that its downstream receptor, the d5-HT7 (Drosophila 5-HT7 homolog) is critical for learning in Drosophila larvae

Summary

Introduction

The TpH-Gal[4] (n = 7) or the UAS-Shits[1] (n = 7) transgenes alone displayed normal olfactory learning when trained at 32 °C and tested 25 °C respectively. TpH-Gal[4]; UAS-ChR2 larvae were exposed to odor (pentyl acetate) in the presence of blue light (BL) but no sucrose. We hypothesize that the expression of 5-HT receptors, those positively coupled to cAMP in the mushroom body, may be essential for learning and memory in Drosophila. In this study we show that the output of serotonergic neurons through points of synaptic contacts on the mushroom body (MB) is required for olfactory associative learning in Drosophila larvae. We demonstrate that the regulation of olfactory associative learning by serotonin is mediated by its downstream receptor (d5-HT7), in a cAMP-dependent manner. We show that spatio-temporal restriction of d5-HT7 expression to the MB is sufficient to rescue olfactory learning deficits in a d5-HT7 null larvae, demonstrating a clear requirement for this receptor in olfactory learning

Methods

Results

Conclusion