Neuropeptides and Behaviors: How Small Peptides Regulate Nervous System Function and Behavioral Outputs

Abstract

One of the reasons that most multicellular animals survive and thrive is because of the adaptable and plastic nature of their nervous systems. For an organism to survive, it is essential for the animal to respond and adapt to environmental changes. This is achieved by sensing external cues and translating them into behaviors through changes in synaptic activity. The nervous system plays a crucial role in constantly evaluating environmental cues and allowing for behavioral plasticity in the organism. Multiple neurotransmitters and neuropeptides have been implicated as key players for integrating sensory information to produce the desired output. Because of its simple nervous system and well-established neuronal connectome, C. elegans acts as an excellent model to understand the mechanisms underlying behavioral plasticity. Here, we critically review how neuropeptides modulate a wide range of behaviors by allowing for changes in neuronal and synaptic signaling. This review will have a specific focus on feeding, mating, sleep, addiction, learning and locomotory behaviors in C. elegans. With a view to understand evolutionary relationships, we explore the functions and associated pathophysiology of C. elegans neuropeptides that are conserved across different phyla. Further, we discuss the mechanisms of neuropeptidergic signaling and how these signals are regulated in different behaviors. Finally, we attempt to provide insight into developing potential therapeutics for neuropeptide-related disorders.

Long-term imaging reveals behavioral plasticity during C. elegans dauer exit

“…At 6 h.a.t, coinciding with the second behavioral switch to post-dauer behavior, the most significantly differentially expressed gene ontology (GO) - term was “neuropeptide signaling pathway” (p-value: 1.66×10-8) (Figure 3f). The differentially expressed genes within this GO-term revealed numerous neuropeptides, comprising both FMRFamide peptides (FLPs) and neuropeptide-like proteins (NLPs), previously described to modulate behavior in C. elegans (47) as well as some of the corresponding receptors (Supplemental Figure S7). We found that almost all (23/24) neuropeptides were downregulated during dauer exit.…”

“…In C. elegans, the dynamic expression of neuropeptides has been described to control several fundamental behavioral programs, e.g. mating (56), feeding (38), sleep (57) and others (47). More specifically, in the context of dauer larvae, previous work has identified increased neuropeptide signaling as an important neuromodulatory event for promoting the dauer entry decision (58, 59).…”

Potentials of Neuropeptides as Therapeutic Agents for Neurological Diseases

“…It would be interesting to determine how such possible mechanisms may be relevant to differential postsynaptic neuronal function. Additionally, there remains an incomplete understanding of the crosstalk occurring between multiple neuropeptides that underlies behavioural processes [ 231 ]. However, it appears that the co-storage and simultaneous release of various neuropeptides presents a way in which neuropeptides can act together in a precise manner to exert actions on post-synaptic neurons.…”

Multisite gating in tonic sensory circuits integrates multimodal context to control persistent behavioral states

“…Animals continuously integrate information from external environment with their past experience and internal states to generate adaptive behavioral states. This context-dependent modification of behavioral states in turn impacts sensory processing, sensory integration and animal's response to the environment (Berridge and Waterhouse, 2003;Bramham and Srebro, 1989;Dave et al, 1998). Animals show transient or persistent modifications in the behavioral state based on shift in integrated valance of the context to ensure survival and maximizes their fitness (Gibson et al, 2015;Jo et al, 2020;Sorrells et al, 2022).…”

“…Moreover, neuron activity recording in vivo and manipulation tools allowing mechanistic dissection at circuit levels can link distinct neuronal activity patterns with different behavioral states (Busch et al, 2012;Ji et al, 2021;Kato et al, 2015;Nichols et al, 2017;Venkatachalam et al, 2016). Genetic analyses in different studies revealed the role of conserved neuromodulatory pathways as dopamine, serotonin, tyramine, octopamine and neuropeptide signaling in mediating behavioral state transitions (Bhardwaj et al, 2018;Bhat et al, 2021;Churgin et al, 2017;Flavell et al, 2013;Oranth et al, 2018). C. elegans can sense and modulate behavioral states in response to wide range of sensory and physiological cues such as touch, odors, light, sound, oxygen, CO2, and temperature from the environment (Bargmann, 2006;Bretscher et al, 2008;Ghosh et al, 2021;Goodman and Sengupta, 2019;Gray et al, 2004;Iliff et al, 2021).…”