Differences in microglia morphological profiles reflect divergent emotional temperaments: insights from a selective breeding model

Microglia play critical roles in healthy brain development and function, as well as the neuropathology underlying a range of brain diseases. Despite evidence for a role of microglia in affective regulation and mood disorders, little is known regarding how variation in microglia status relates to individual differences in emotionality. Using a selective breeding model, we have generated rat lines with unique temperamental phenotypes that reflect broad emotional traits: bred low responder rats (bLRs) are novelty-averse and model a passive coping style, whereas bred high responder rats (bHRs) are highly exploratory and model an active coping style. To identify a functional role of microglia in these phenotypes, we administered minocycline, an antibiotic with potent microglia inhibiting properties and observed shifts in forced swim, sucrose preference, and social interaction behaviors in bLRs. Using detailed anatomical analyses, we compared hippocampal microglia profiles of bHRs and bLRs and found that although the lines had similar numbers of microglia, selective breeding was associated with a shift in the morphological features of these cells. Specifically, microglia from bLRs were characterized by a hyper-ramified morphology, with longer processes and more complicated branching patterns than microglia from bHRs. This morphology is thought to reflect an early stage of microglia activation and suggests that bLR microglia are in a reactive state even when animals are not overtly challenged. Taken together, our results provide novel evidence linking variation in inborn temperament with differences in the baseline status of microglia and implicate a role for microglia in shaping enduring emotional characteristics.