Pair Bond-Induced Affiliation and Aggression in Male Prairie Voles Elicit Distinct Functional Connectivity in the Social Decision-Making Network

Abstract

Complex social behaviors are governed by a neural network theorized to be the social decision-making network (SDMN). However, this theoretical network is not tested on functional grounds. Here, we assess the organization of regions in the SDMN using c-Fos, to generate functional connectivity models during specific social interactions in a socially monogamous rodent, the prairie voles (Microtus ochrogaster). Male voles displayed robust selective affiliation toward a female partner, while exhibiting increased threatening, vigilant, and physically aggressive behaviors toward novel males and females. These social interactions increased c-Fos levels in eight of the thirteen brain regions of the SDMN. Each social encounter generated a distinct correlation pattern between individual brain regions. Thus, hierarchical clustering was used to characterize interrelated regions with similar c-Fos activity resulting in discrete network modules. Functional connectivity maps were constructed to emulate the network dynamics resulting from each social encounter. Our partner functional connectivity network presents similarities to the theoretical SDMN model, along with connections in the network that have been implicated in partner-directed affiliation. However, both stranger female and male networks exhibited distinct architecture from one another and the SDMN. Further, the stranger-evoked networks demonstrated connections associated with threat, physical aggression, and other aversive behaviors. Together, this indicates that distinct patterns of functional connectivity in the SDMN can be detected during select social encounters.

The neural circuits of monogamous behavior

“…Accordingly, differences in levels of estrogen-receptor α (ERα) expression in the MeA, mPOA, and the VMN are also associated with monogamous behavior and parental care in mandarin voles (Wu et al, 2011). (Aragona et al, 2003;Gingrich et al, 2005), d (López-Gutiérrez et al, 2021, e (Aragona et al, 2006), f (Bales et al, 2007), g (Maninger et al, 2017b), h (Arias Del Razo et al, 2020), i (Hostetler et al, 2017), by D1 receptor antagonist [11C]-SCH2339 binding detection, j (Maninger et al, 2017b), k (Burkett et al, 2011;Resendez et al, 2013Resendez et al, , 2016; l (Lei et al, 2010), m (Lambert et al, 2021), n (Gossman et al, 2021), o (King et al, 2016), p (Ophir et al, 2008b), q (Liu et al, 2001;), r (Pitkow et al, 2001;), s (Witczak et al, 2018), t (Cavanaugh et al, 2014(Cavanaugh et al, , 2018a With respect to OT variants and their impact on behavior, interesting discoveries have been made. Phylogenetic evidence has shown not only OT genetic sequence differences across closely related species, but also a functional cross-talk between AVP and OT, and structural variations in the expressed nonapeptides that could subsequently impact their involvement in neural circuits (French et al, 2016;Pierce et al, 2020).…”

“…Studies employing immediate early gene expression have led to important discoveries on the role of brain regions involved in rodent pair bonding. The expression of c-Fos, product of the immediate early gene c-fos, has been widely used because it serves as an indicator of recent neuronal activity and has been used create functional connectivity models during specific social interactions ( Gossman et al, 2021 ). In monogamous voles, c-Fos expression has been assessed in several brain regions of the SMDN and has underpinned important neurobiological mechanisms that underlie pair-bond formation.…”

“…Its conceptual application has been extended to the co-expression patterns of immediate early genes ( Tanimizu et al, 2017 ). This connectivity has already been studied between regions of the SMDN during different social interactions in pair-bonded male prairie voles through c-Fos expression patterns ( Gossman et al, 2021 ). The social interactions assessed in this study were the exposure to their pair bonded partner, a same-sex stranger, and an opposite-sex stranger.…”

“…Specifically, evoked brain activity upon exposure to their pair bonded partner was reported in the mPOA, BNST, LS, and VP, consistent with the findings of Gobrogge and coworkers ( Gobrogge et al, 2007 ). Moreover, the mPOA, BNST, LS, and the VP were also activated upon exposure to a same-sex stranger, but only the VMH activity increased upon exposure to all social encounters ( Gossman et al, 2021 ). In addition to the analysis of c-Fos brain induced activity, Gossman et al (2021) also analyzed coactivation patterns across regions using correlational models, hierarchical cluster analysis, and graph theory-derived network modeling.…”

“…Moreover, the mPOA, BNST, LS, and the VP were also activated upon exposure to a same-sex stranger, but only the VMH activity increased upon exposure to all social encounters ( Gossman et al, 2021 ). In addition to the analysis of c-Fos brain induced activity, Gossman et al (2021) also analyzed coactivation patterns across regions using correlational models, hierarchical cluster analysis, and graph theory-derived network modeling. The partner-related network incorporated the AH, LS, mPOA, and the VP regions suggested to compose the social behavioral network ( Newman, 1999 ; O’Connell and Hofmann, 2011 ) and involved in affiliative behaviors in the prairie vole ( Curtis and Wang, 2003 ; Cushing et al, 2003 ; Lim and Young, 2004 ; Gossman et al, 2021 ).…”