A test of the social behavior network reveals differential patterns of neural responses to social novelty in bonded, but not non-bonded, male prairie voles

Abstract

The social behavior network (SBN) has provided a framework for understanding the neural control of social behavior. The original SBN hypothesis proposed this network modulates social behavior and should exhibit distinct patterns of neural activity across nodes, which correspond to distinct social contexts. Despite its tremendous impact on the field of social neuroscience, no study has directly tested this hypothesis. Thus, we assessed Fos responses across the SBN of male prairie voles (Microtus ochrogaster). Virgin/non-bonded and pair bonded subjects were exposed to a sibling cagemate or pair bonded partner, novel female, novel male, novel meadow vole, novel object, or no stimulus. Inconsistent with the original SBN hypothesis, we did not find profoundly different patterns of neural responses across the SBN for different contexts, but instead found that the SBN generated significantly different patterns of activity in response to social novelty in pair bonded, but not non-bonded males. These findings suggest that non-bonded male prairie voles may perceive social novelty differently from pair bonded males or that SBN functionality undergoes substantial changes after pair bonding. This study reveals novel information about bond-dependent, context-specific neural responsivity in male prairie voles and suggests that the SBN may be particularly important for processing social salience. Further, our study suggests there is a need to reconceptualize the framework of how the SBN modulates social behavior.

Keywords: Aggression; Brain network; Prairie vole; Social behavior; Social behavior network.

Figure 1:. Behavior in the IEG test.

(A) Mean ± SEM time (seconds, s) to approach the stimulus for all subjects combined. (B) Mean ± SEM time spent engaging in prosocial behavior with the stimulus for all subjects combined. (C) Mean ± SEM time spent engaging in aggressive behavior with the stimulus, which differed between pair bonded and non-bonded males. Dots represent individual data points. Shared letters over bars represent statistical similarity.

Figure 2.. Fos expression across social contexts.

Visualization of average z-scored Fos-ir expression for all subjects, excluding the Pair Bonded Partner context (which included data from partnered animals only) and Non-Bonded Cagemate context (non-bonded animals only).

Figure 3.. GLM analysis of brain region-specific Fos expression.

Mean ± SEM Fos-ir expression across contexts in the (A) lateral septum (LS), (B) anterior hypothalamus (AH), (C) ventromedial hypothalamus (VMH), and (D) periaqueductal gray (PAG). Mean ± SEM Fos-ir expression interactions between Group and Context in the (E-F) bed nucleus of the stria terminalis (BST), (G-H) preoptic area (POA), and (I-J) medial amygdala (MeA). Dots represent individual data points. Asterisks indicate statistical significance. Shared letters over bars represent statistical similarity whereas different letters over bars indicate statistically significant differences.

Figure 4.. Mean Fos-ir+ cell counts across the SBN.

Mean ± SEM Fos-ir expression across SBN nodes in non-bonded (left) and pair bonded (right) male prairie voles across contexts. Color gradation represents mean Fos-ir cell counts with dark blue representing 0 cells and dark red representing greater than 200 cells. Abbreviations: anterior hypothalamus (AH), bed nucleus of the stria terminalis (BST), lateral septum (LS), medial amygdala (MeA), periaqueductal gray (PAG), preoptic area (POA), ventromedial hypothalamus (VMH).

Figure 5.. Classification accuracy matrices.

Classification accuracies based on pairwise comparisons of patterns of Fos expression across the SBN of (A) non-bonded and (B) pair bonded male prairie voles between two stimulus Context conditions. (C) Classification accuracies and pairwise comparisons of patterns of Fos expression across the SBN between non-bonded and pair bonded vole Groups exposed to the same stimulus condition. Color gradation represents classification accuracy with dark blue representing a less than or equal to accuracy of 50% and dark red representing 100% accuracy of correct classification. A dagger represents statistical significance before correction for multiple comparisons whereas an asterisk represents statistical significance after correction for multiple comparisons.