Characterization of the relaxin family peptide receptor 3 system in the mouse bed nucleus of the stria terminalis. Issue 16 (13th April 2019)

• Record Type: Journal Article
• Authors: Ch'ng, Sarah S.; Fu, Jingjing; Brown, Robyn M.; Smith, Craig M.; Hossain, Mohammed Akhter; McDougall, Stuart J.; Lawrence, Andrew J.
• Is Part Of: Journal of comparative neurology. Volume 527:Issue 16(2019)
• Page Start: 2615
• Page End: 2633
• Publication Date: 2019-04-13
• Subjects: bed nucleus of the stria terminalis -- corticotropin‐releasing factor -- relaxin‐3 -- RRID:AB_141607 -- RRID:AB_141637 -- RRID:AB_141844 -- RRID:AB_142672 -- RRID:AB_2336132 -- RRID:AB_2340375 -- RRID:AB_2536183 -- RRID:AB_2619710 -- RRID:AB_300798 -- RRID:AB_309787 -- RRID:AB_477329 -- RRID:AB_477652 -- RRID:AB_634520 -- RRID:AB_887883 -- RRID:IMSR_JAX:007914 -- RRID:MMRRC_036667‐UCD -- RXFP3 -- stress; Comparative neurobiology -- Periodicals; Neurology -- Periodicals; 616
• DOI: 10.1002/cne.24695
• Languages: English
• ISSNs: 0021-9967

Abstract

Abstract: 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. Abstract : We have characterized the distribution, neurotransmitter phenotype, and electrophysiological properties of neurons expressing relaxin family peptide receptor 3 (RXFP3) in the bed nucleus of the stria terminalis (BNST) using RXFP3‐Cre reporter mice. BNST RXFP3+ neurons are neurochemically heterogeneous and can be classified into four basic types in terms of basal firing properties. Chronic stress alters the relative proportions of different BNST RXFP3+ neuronal subtypes consistent with experience‐dependent plasticity.