Neuropeptide and Behaviours

 Efficient circuit analysis to identify minimal neural circuitry to regulate behaviour

Studies of neuropeptide and peptide hormone signaling are coming of age in Drosophila due to rapid developments in molecular genetics approaches that overcome the difficulties caused by the small size of the fly. In addition we have genome-wide information on genes involved in peptide signaling, and growing pools of peptidomics data. A large number of different neuropeptides has been identified in a huge variety of neuron types in different parts of the Drosophila nervous system and cells in other locations. This review addresses questions related to peptidergic signaling in the Drosophila nervous system, especially how peptides regulate physiology and behavior during development and in the mature fly. We first summarize novel findings on neuropeptide precursor genes, processed bioactive peptides and their cognate receptors. Thereafter we provide an overview of the physiological and behavioral roles of peptide signaling in Drosophila. These roles include regulation of development, growth, feeding, metabolism, reproduction, homeostasis, and longevity, as well as neuromodulation in learning and memory, olfaction and locomotor control. The substrate of this signaling is the peptide products of about 42 precursor genes expressed in different combinations in a variety of neuronal circuits or that act as circulating hormones. Approximately 45 G-protein-coupled peptide receptors are known in Drosophila and for most of these the ligands have been identified. Functions of some peptides are better understood than others, and much work remains to reveal the spectrum of roles neuropeptides and peptide hormones play in the daily life of a fly. Nässel, D. R., & Winther, A. M. E. (2010). Drosophila neuropeptides in regulation of physiology and behavior. Progress in Neurobiology, 92(1), 42–104. doi:10.1016/j.pneurobio.2010.04.010
In short, neuropeptides is a chain of amino acids that is released either into the blood where it activates receptors in our body, or directly into the brain where it can activate receptors in our brain. They are neuronal signaling molecules that influence the activity of the brain in specific ways. Different neuropeptides are involved in a wide range of brain functions, including analgesia, reward, food intake, metabolism, reproduction, social behaviors, learning and memory.​ In short, neuropeptides represent the largest single class of signal compounds and involved in regulation of development, growth, reproduction, metabolism and behavior of insects (almost every aspect of insect life). 

One cannot screen all the neurons responsible for certain types of behavior. Since neuropeptides and their receptors expressing neurons are limited and specifically involved with certain types of behaviors, targeting neuropeptide signaling when analyzing behavior helps to reduce the possible candidates of neurons involved with those behaviors. 

Neuropeptides usually interact with G protein- coupled receptors (GPCRs), through which they act as slow neurotransmitters or neuromodulators. GPCR receptors are the major target for many contemporary drugs. In 2003, seven of the twenty most prescribed drugs interact with GPCRs, representing a total sales number of 14.3 billion US dollars. Overall, GPCRs are the molecular target for over 30% of all currently marketed drugs, making the GPCR superfamily one of the most valuable target molecules for drug development. Likewise, GPCRs can also be used as pesticide targets in agricultural applications. Moreover, GPCRs gains growing interest as promising candidate targets for the development of a new generation of species- and receptor- specific insect control agents that may generate fewer side effects.

In our previous works, we successfully identified specific GPCR modulate specific fruit fly behavior. Extending these knowledge will lead to screen and develop such chemicals that specifically binds to insect neuropeptide receptors. This strategy may help to develop successful pesticide control that minimizes potential and harmful side effects of those drugs. Moreover, if we combine this knowledge with recent CRISPR/Cas9 chain reaction technology, we can generate very safe and specific targeting insecticide to help agricultural outcomes. 

image from Ledford, H. (2015). CRISPR, the disruptor. Nature, 522(7554), 20–24.

Useful Links and Articles

 Neuropeptide and behaviors

This is the most intriguing review describing the neuropeptide system regulating behaviors and physiology from insects to mammals. 

A powerful new CRISPR/Cas9 tool can be used to produce homozygous mutations within a generation, but scientists call for caution.