Serotonin is a monoamine neurotransmitter which acts as an important regulator of physiological and behavioral processes throughout the animal kingdom. In humans, disruption of the serotonergic system has been known to be associated with several diseases such as depression and schizophrenia (1).
Insects are highly attractive models for studying the serotonergic functions because individual neurons can be identified from one animal to another. This allows precise assessment of the anatomical distribution, development, and neurophysiological properties of the serotonergic neurons. In particular, Drosophila melanogaster represents a favorable model organism to dissect neuronal circuits genetically and to manipulate the activity of defined neuronal populations experimentally.
D. melanogaster expresses orthologs of three of the seven mammalian receptor family: Dm5-HT1A/B, Dm5-HT2A/B, and Dm5-HT7 (2-4). In this seminar, I would like to focus on the function of Dm5-HT7, which is relatively less characterized.
Like the other receptors, Dm5-HT7 is expressed in the adult brain. The expression is highly localized to large field R-neurons that innervate the ellipsoid body, as well as small cell groups that tightly cluster with PDF (peptide dispersing factor)-expressing cells (5). Pharmacological and genetic knockdown of Dm5-HT7 produced courting and mating deficits (6). Early behaviors were not significantly affected, whereas later behaviors were significantly reduced and successful copulation even eliminated. Since the general olfaction and the locomotor activity are not altered by the treatment, it is likely that the deficiency of the mating behavior is not due to physiological problems but rather the motivation of the flies.
Little is known about the exact function of the ellipsoid body, but the overall structure is believed to be involved in mediating higher order behaviors including aspects of learning and memory and stress responses (7). Therefore, Dm5-HT7-expressing neurons may be involved in other behaviors as well. Furthermore, the PDF-expressing neurons are known to be the members of the circadian clock circuity, so the Dm5-HT7-expressing neurons may also be involved (8). Further study of Dm5-HT7 may lead to dissection of the neural circuit of high order behaviors, which may in turn unveil the mechanism of serotonergic function in humans and other animals.
[References]
1. Berger M, Gray JA, & Roth BL (2009) The Expanded Biology of Serotonin. Annual Review of Medicine 60:355-366.
2. Alekseyenko OV, et al. (2014) Single Serotonergic Neurons that Modulate Aggression in Drosophila. Current Biology 24(22):2700-2707.
3. Yuan Q, Joiner WJ, & Sehgal A (2006) A sleep-promoting role for the Drosophila serotonin receptor 1A. Current Biology 16(11):1051-1062.
4. Pooryasin A & Fiala A (2015) Identified Serotonin-Releasing Neurons Induce Behavioral Quiescence and Suppress Mating in Drosophila. Journal of Neuroscience 35(37):12792-12812.
5. Gnerer JP, Venken KJT, & Dierick HA (2015) Gene-specific cell labeling using MiMIC transposons. Nucleic Acids Research 43(8).
6. Becnel J, Johnson O, Luo JN, Nassel DR, & Nichols CD (2011) The Serotonin 5-HT(7)Dro Receptor Is Expressed in the Brain of Drosophila, and Is Essential for Normal Courtship and Mating. Plos One 6(6).
7. Johnson O, Becnel J, & Nichols CD (2011) SEROTONIN RECEPTOR ACTIVITY IS NECESSARY FOR OLFACTORY LEARNING AND MEMORY IN DROSOPHILA MELANOGASTER. Neuroscience 192:372-381.
8. Yuan Q, Lin FJ, Zheng XZ, & Sehgal A (2005) Serotonin modulates circadian entrainment in Drosophila. Neuron 47(1):115-127.