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Characterization of the relaxin family peptide receptor 3 system in the mouse bed nucleus of the stria terminalis
journal contribution
posted on 2019-11-01, 00:00 authored by S S Ch'ng, J Fu, R M Brown, Craig SmithCraig Smith, M A Hossain, S J McDougall, A J Lawrence© 2019 Wiley Periodicals, Inc. The bed nucleus of the stria terminalis (BNST) is a critical node involved in stress and reward-related behaviors. Relaxin family peptide receptor 3 (RXFP3) signaling in the BNST has been implicated in stress-induced alcohol seeking behavior. However, the neurochemical phenotype and connectivity of BNST RXFP3-expressing (RXFP3+) cells have yet to be elucidated. We interrogated the molecular signature and electrophysiological properties of BNST RXFP3+ neurons using a RXFP3-Cre reporter mouse line. BNST RXFP3+ cells are circumscribed to the dorsal BNST (dBNST) and are neurochemically heterogeneous, comprising a mix of inhibitory and excitatory neurons. Immunohistochemistry revealed that ~48% of BNST RXFP3+ neurons are GABAergic, and a quarter of these co-express the calcium-binding protein, calbindin. A subset of BNST RXFP3+ cells (~41%) co-express CaMKIIα, suggesting this subpopulation of BNST RXFP3+ neurons are excitatory. Corroborating this, RNAscope® revealed that ~35% of BNST RXFP3+ cells express vVGluT2 mRNA, indicating a subpopulation of RXFP3+ neurons are glutamatergic. RXFP3+ neurons show direct hyperpolarization to bath application of a selective RXFP3 agonist, RXFP3-A2, while around 50% of cells were depolarised by exogenous corticotrophin releasing factor. In behaviorally naive mice the majority of RXFP3+ neurons were Type II cells exhibiting Ih and T type calcium mediated currents. However, chronic swim stress caused persistent plasticity, decreasing the proportion of neurons that express these channels. These studies are the first to characterize the BNST RXFP3 system in mouse and lay the foundation for future functional studies appraising the role of the murine BNST RXFP3 system in more complex behaviors.
History
Journal
Journal of comparative neurologyVolume
527Issue
16Pagination
2615 - 2633Publisher
WileyLocation
Chichester, Eng.Publisher DOI
ISSN
0021-9967eISSN
1096-9861Language
engPublication classification
C1 Refereed article in a scholarly journalCopyright notice
2019, Wiley Periodicals, Inc.Usage metrics
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Keywords
Science & TechnologyLife Sciences & BiomedicineNeurosciencesZoologyNeurosciences & Neurologybed nucleus of the stria terminaliscorticotropin-releasing factorrelaxin-3RRID:AB_141607RRID:AB_141637RRID:AB_141844RRID:AB_142672RRID:AB_2336132RRID:AB_2340375RRID:AB_2536183RRID:AB_2619710RRID:AB_300798RRID:AB_309787RRID:AB_477329RRID:AB_477652RRID:AB_634520RRID:AB_887883RRID:IMSR_JAX:007914RRID:MMRRC_036667-UCDRXFP3stressCORTICOTROPIN-RELEASING-FACTORVENTRAL TEGMENTAL AREASTRESS-INDUCED REINSTATEMENTDEPENDENT PROTEIN-KINASEHYPOTHALAMIC PARAVENTRICULAR NUCLEUSRECTIFYING POTASSIUM CHANNELSGLUTAMIC-ACID DECARBOXYLASECUE-INDUCED REINSTATEMENTCOCAINE-SEEKINGCALBINDIN D-28KZoology
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