Endocrine cybernetics: neuropeptides as molecular switches in behavioural decisions

Abstract

Plasticity in animal behaviour relies on the ability to integrate external and internal cues from the changing environment and hence modulate activity in synaptic circuits of the brain. This context-dependent neuromodulation is largely based on non-synaptic signalling with neuropeptides. Here, we describe select peptidergic systems in the Drosophila brain that act at different levels of a hierarchy to modulate behaviour and associated physiology. These systems modulate circuits in brain regions, such as the central complex and the mushroom bodies, which supervise specific behaviours. At the top level of the hierarchy there are small numbers of large peptidergic neurons that arborize widely in multiple areas of the brain to orchestrate or modulate global activity in a state and context-dependent manner. At the bottom level local peptidergic neurons provide executive neuromodulation of sensory gain and intrinsically in restricted parts of specific neuronal circuits. The orchestrating neurons receive interoceptive signals that mediate energy and sleep homeostasis, metabolic state and circadian timing, as well as external cues that affect food search, aggression or mating. Some of these cues can be triggers of conflicting behaviours such as mating versus aggression, or sleep versus feeding, and peptidergic neurons participate in circuits, enabling behaviour choices and switches.

System-wide mapping of neuropeptide-GPCR interactions inC. elegans

“…Although bioactive peptides are also secreted from non-neuronal tissues, most are released in the nervous system and signal via G proteincoupled receptors (GPCRs). Neuropeptides are among the most ancient neuronal messengers, likely predating the evolution of neurons 1,2 , and many peptidergic systems have broadlyconserved functions across bilaterian animals [3][4][5][6][7] . Because of their crucial roles, neuropeptidereceptor systems are increasingly gaining traction as potential therapeutic targets for human diseases [8][9][10][11] .…”

Selection and Comparative Gene Expression of Midgut-Specific Targets for Drosophila suzukii

“…DS10_00008044 (GenBank Accession No. XP_036675103) was identified with the receptor of neuropeptide F (NPF), which has various functions including food search, intake, and odor perception important in the regulation of feeding activities in insects [ 13 , 14 ]. In Drosophila , the first NPF receptor (NPF-R) exhibits a similar pattern of localization in larvae, as the NPF ligand gene that is expressed in the brain and in the midgut for regulation of feeding and digestion [ 47 ].…”

“…Insect neuropeptides (NPs) and G protein-coupled receptors (GPCRs) are involved in a variety of critical physiological processes such as homeostasis, feeding, digestion, excretion, circulation, reproduction, and metamorphosis during insect life stages [ 13 , 14 ]. Therefore, insect NPs and their GPCRs have been proposed as potential targets for decades [ 15 , 16 , 17 ].…”

The incidence of candidate binding sites for β-arrestin in Drosophila neuropeptide GPCRs

“…However, this conclusion is speculative as such mechanisms are largely unknown in the fly. A sophisticated genetic model system like Drosophila , coupled with the rich history of neuroendocrine and neuropeptide physiology in insects (64–67), provides a novel complimentary path forward, for a better understanding of β-arrestin regulatory biology. Given the prominent role of GPCRs in normal signaling, and as targets for a large fraction of modern therapeutics (68, 69), the significance of such model studies could be substantial.…”