Wild mice with different social network sizes vary in brain gene expression

Abstract

Background: Appropriate social interactions influence animal fitness by impacting several processes, such as mating, territory defense, and offspring care. Many studies shedding light on the neurobiological underpinnings of social behavior have focused on nonapeptides (vasopressin, oxytocin, and homologues) and on sexual or parentoffspring interactions. Furthermore, animals have been studied under artificial laboratory conditions, where the consequences of behavioral responses may not be as critical as when expressed under natural environments, therefore obscuring certain physiological responses. We used automated recording of social interactions of wild house mice outside of the breeding season to detect individuals at both tails of a distribution of egocentric network sizes (characterized by number of different partners encountered per day). We then used RNA-seq to perform an unbiased assessment of neural differences in gene expression in the prefrontal cortex, the hippocampus and the hypothalamus between these mice with naturally occurring extreme differences in social network size. Results: We found that the neurogenomic pathways associated with having extreme social network sizes differed between the sexes. In females, hundreds of genes were differentially expressed between animals with small and large social network sizes, whereas in males very few were. In males, X-chromosome inactivation pathways in the prefrontal cortex were the ones that better differentiated animals with small from those with large social network sizes animals. In females, animals with small network size showed up-regulation of dopaminergic production and transport pathways in the hypothalamus. Additionally, in females, extracellular matrix deposition on hippocampal neurons was higher in individuals with small relative to large social network size. Conclusions: Studying neural substrates of natural variation in social behavior in traditional model organisms in their habitat can open new targets of research for understanding variation in social behavior in other taxa.

Social Interactions of Dat-Het Epi-Genotypes Differing for Maternal Origins: The Development of a New Preclinical Model of Socio-Sexual Apathy

“…A wide body of literature has demonstrated that external stimuli, such as stress, often result in significant changes in dopamine (DA) and noradrenaline (NE) concentrations in the social brain regions [2,3]. Indeed, DA neurons, located in the ventral tegmental area (VTA) and substantia nigra (SN), innervate brain regions relevant to social play and affiliative behavior, such as the prefrontal cortex, the hippocampus, the striatum and hypothalamus [4]. When subjects are in contact with social stimuli, emotional processes having a positive or negative valence involve DA neurons originating in VTA [5,6].…”

“…In the present study, we employed immunofluorescence to assess the expression of NET in the prefrontal cortex, hippocampus and hypothalamus, brain regions relevant to social behavior [4] where we observed altered NE levels in heterozygous DAT rats [14].…”

Neurogenomic landscape associated with status-dependent cooperative behavior

“…Using previously developed microdissection protocols (Horton et al . 2020), we conducted transcriptome-level sampling of the pituitary, testes, and 10 brain nuclei comprising the entire SBN and a portion of the mesolimbic reward system (MRS) (Lopes and König 2020; Bentz et al . 2021b; Kabelik et al .…”

“…Using previously developed microdissection protocols (Horton et al 2020), we conducted transcriptome-level sampling of the pituitary, testes, and 10 brain nuclei comprising the entire SBN and a portion of the mesolimbic reward system (MRS) (Lopes and König 2020;Bentz et al 2021b;Kabelik et al 2021;Bentz et al 2021a;Antunes et al 2021) (Figure 1F, Table S1.2) from nine territorial and seven floater males. A subset of these individuals were characterized for testosterone and cooperative phenotypes (Figure 1DE).…”

Early social deprivation shapes neuronal programming of the social decision‐making network in a cooperatively breeding fish

“…Monoaminergic activity, particularly the activity of the dopaminergic and serotonergic systems, plays a crucial role in regulating behaviour (Soares et al, 2010 ; Winberg & Thörnqvist, 2016 ). In mice, for instance, short‐term maternal separation up‐regulates drd1 in the hippocampus (Köhler et al, 2019 ), and females with smaller social networks show an up‐regulation of dopaminergic production (Lopes & König, 2020 ). Similarly to other neurological systems, during early‐life monoaminergic systems require appropriate social stimulation to achieve normal development.…”