Neuropeptides, such as neuropeptide S (NPS) and oxytocin (OXT) represent potential options for the treatment of anxiety disorders due to their potent anxiolytic profile. In this study, we aimed to reveal the mechanisms underlying the behavioral action of NPS, and present a chain of evidence that the effects of NPS within the hypothalamic paraventricular nucleus (PVN) are mediated via actions on local OXT neurons in male Wistar rats. First, retrograde studies identified NPS fibers originating in the brainstem locus coeruleus and projecting to the PVN. Fluorescence-activated cell sorting identified prominent NPS receptor (NPSR) expression in PVN-OXT neurons. Using genetically encoded calcium indicators, we further demonstrated that NPS reliably induces a transient increase in intracellular Ca(2+) concentration in a subpopulation of OXT neurons - an effect mediated by NPSR. In addition, intracerebroventricular (icv) NPS evoked a significant somato-dendritic release of OXT within the PVN as assessed by microdialysis in combination with a highly sensitive radioimmunoassay. Finally, we could show that the anxiolytic effect of NPS seen after icv or intra-PVN infusion requires responsive OXT neurons of the PVN and locally released OXT. Thus, pharmacological blockade of OXT receptors as well as chemogenetic silencing of OXT neurons within the PVN prevented the effect of synthetic NPS. In conclusion, our results indicate a significant role of the OXT system in mediating the effects of NPS on anxiety, and fill an important gap in our understanding of brain neuropeptide interactions in the context of regulation of emotional behavior within the hypothalamus.SIGNIFICANCE STATEMENTGiven the rising scientific interest in neuropeptide research in the context of emotional and stress-related behaviors, our findings demonstrate a novel intra-hypothalamic mechanism involving paraventricular oxytocin neurons that express the neuropeptide S receptor. These neurons respond with transient Ca(2+) increase and somato-dendritic oxytocin release following neuropeptide S stimulation. Thereby, oxytocin neurons seem essential for neuropeptide S-induced anxiolysis, as this effect was blocked by pharmacological and chemogenetic inhibition of the oxytocin system.
Pharmacology, Toxicology and Pharmaceutical Science
2
3%
Other
6
8%
Unknown
27
35%
Attention Score in Context
Attention Score in Context
This research output has an Altmetric Attention Score of 5. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 19 September 2019.
All research outputs
#10,128,433
of 34,400,738 outputs
Outputs from Journal of Neuroscience
#10,909
of 23,401 outputs
Outputs of similar age
#118,396
of 376,733 outputs
Outputs of similar age from Journal of Neuroscience
#127
of 265 outputs
Altmetric has tracked 34,400,738 research outputs across all sources so far. This one has received more attention than most of these and is in the 70th percentile.
So far Altmetric has tracked 23,401 research outputs from this source. They typically receive a lot more attention than average, with a mean Attention Score of 15.3. This one has gotten more attention than average, scoring higher than 53% of its peers.
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We're also able to compare this research output to 265 others from the same source and published within six weeks on either side of this one. This one has gotten more attention than average, scoring higher than 52% of its contemporaries.
