The importance of distinguishing individual differences in 'social impact' versus 'social responsiveness' when quantifying indirect genetic effects on the evolution of social plasticity.

Social evolution and the dynamics of social interactions have previously been studied under the frameworks of quantitative genetics and behavioural ecology. In quantitative genetics, indirect genetic effects of social partners on the socially plastic phenotypes of focal individuals typically lack crucial detail already included in treatments of social plasticity in behavioural ecology. Specifically, whilst focal individuals (e.g. receivers) may show variation in their 'responsiveness' to the social environment, individual social partners (e.g. signallers) may have a differential 'impact' on focal phenotypes. Here we propose an integrative framework, that highlights the distinction between responsiveness versus impact in indirect genetic effects for a range of behavioural traits. We describe impact and responsiveness using a reaction norm approach and provide statistical models for the assessment of these effects of focal and social partner identity in different types of social interactions. By providing such a framework, we hope to stimulate future quantitative research investigating the causes and consequences of social interactions on phenotypic evolution.

Impaired mitochondrial complex I function as a candidate driver in the biological stress response and a concomitant stress-induced brain metabolic reprogramming in male mice.

Mitochondria play a critical role in bioenergetics, enabling stress adaptation, and therefore, are central in biological stress responses and stress-related complex psychopathologies. To investigate the effect of mitochondrial dysfunction on the stress response and the impact on various biological domains linked to the pathobiology of depression, a novel mouse model was created. These mice harbor a gene trap in the first intron of the Ndufs4 gene (Ndufs4GT/GT mice), encoding the NDUFS4 protein, a structural component of complex I (CI), the first enzyme of the mitochondrial electron transport chain. We performed a comprehensive behavioral screening with a broad range of behavioral, physiological, and endocrine markers, high-resolution ex vivo brain imaging, brain immunohistochemistry, and multi-platform targeted mass spectrometry-based metabolomics. Ndufs4GT/GT mice presented with a 25% reduction of CI activity in the hippocampus, resulting in a relatively mild phenotype of reduced body weight, increased physical activity, decreased neurogenesis and neuroinflammation compared to WT littermates. Brain metabolite profiling revealed characteristic biosignatures discriminating Ndufs4GT/GT from WT mice. Specifically, we observed a reversed TCA cycle flux and rewiring of amino acid metabolism in the prefrontal cortex. Next, exposing mice to chronic variable stress (a model for depression-like behavior), we found that Ndufs4GT/GT mice showed altered stress response and coping strategies with a robust stress-associated reprogramming of amino acid metabolism. Our data suggest that impaired mitochondrial CI function is a candidate driver for altered stress reactivity and stress-induced brain metabolic reprogramming. These changes result in unique phenomic and metabolomic signatures distinguishing groups based on their mitochondrial genotype.