Title | Relaxin-3/RXFP3 signalling in mouse hypothalamus: no effect of RXFP3 activation on corticosterone, despite reduced presynaptic excitatory input onto paraventricular CRH neurons in vitro. |
Publication Type | Journal Article |
Year of Publication | 2017 |
Authors | Zhang, C, D V. Baimoukhametova, C M. Smith, J S. Bains, and Andrew L. Gundlach |
Journal | Psychopharmacology (Berl) |
Volume | 234 |
Issue | 11 |
Pagination | 1725-1739 |
Date Published | 2017 Jun |
ISSN | 1432-2072 |
Keywords | Animals, Corticosterone, Corticotropin-Releasing Hormone, Female, Hypothalamo-Hypophyseal System, Hypothalamus, Male, Mice, Mice, Inbred C57BL, Mice, Knockout, Neurons, Paraventricular Hypothalamic Nucleus, Pituitary-Adrenal System, Presynaptic Terminals, Receptors, G-Protein-Coupled, Signal Transduction |
Abstract | Relaxin-3/RXFP3 signalling is proposed to be involved in the neuromodulatory control of arousal- and stress-related neural circuits. Furthermore, previous studies in rats have led to the proposal that relaxin-3/RXFP3 signalling is associated with activation of the hypothalamic-pituitary-adrenal axis, but direct evidence for RXFP3-related actions on the activity of hypothalamic corticotropin-releasing hormone (CRH) neurons is lacking. In this study, we investigated characteristics of the relaxin-3/RXFP3 system in mouse hypothalamus. Administration of an RXFP3 agonist (RXFP3-A2) intra-cerebroventricularly or directly into the paraventricular nucleus of hypothalamus (PVN) of C57BL/6J mice did not alter corticosterone levels. Similarly, there were no differences between serum corticosterone levels in Rxfp3 knockout (C57BL/6J) and wild-type mice at baseline and after stress, despite detection of the predicted stress-induced increases in serum corticosterone. We examined the nature of the relaxin-3 innervation of PVN in wild-type mice and in Crh-IRES-Cre;Ai14 mice that co-express the tdTomato fluorophore in CRH neurons, identifying abundant relaxin-3 fibres in the peri-PVN region, but only sparse fibres associated with densely packed CRH neurons. In whole-cell voltage-clamp recordings of tdTomato-positive CRH neurons in these mice, we observed a reduction in sEPSC frequency following local application of RXFP3-A2, consistent with an activation of RXFP3 on presynaptic glutamatergic afferents in the PVN region. These studies clarify the relationship between relaxin-3/RXFP3 inputs and CRH neurons in mouse PVN, with implications for the interpretation of current and previous in vivo studies and future investigations of this stress-related signalling network in normal and transgenic mice, under normal and pathological conditions. |
DOI | 10.1007/s00213-017-4575-z |
Alternate Journal | Psychopharmacology (Berl.) |
PubMed ID | 28314951 |