Abstract
Early Life Adversity (ELA) significantly increases the later risk for depression with sex disparities in humans. Depression has been associated with disturbances in the hedonic perception of odorants. Olfaction serves a primary role in social interactions, food intake, and hedonic responding to daily pleasures. Thus, the study of altered olfactory perception and hedonic processing of chemosensory cues after ELA may provide insights into basic neurobiological disturbance underlying pathology. Further, such studies may identify key pathways that impact quality of life, contributing to the development and severity of depressive symptoms as well as sex differences in risk. Here, we used the limited bedding and nesting protocol in mice to model ELA in the form of fragmented maternal care. The aim of this study was to determine whether ELA altered the hedonic processing of odorants in adult male and female mice, and to identify neural substrates underlying those effects. First, we found that male and female pups showed delays in somatic growth around the time of ELA but that females quickly compensate for this loss during the peri-adolescent period, an effect that was not as robust in males. Finally, we found evidence of depressive-like outcomes and altered perception of pleasant odorants in adult male but not female mice with history of ELA. We used fine structural analysis of neurons, cellular imaging and fiber-photometry to decipher the neural bases of ELA. We found sex-selective effects on the morphology and activity of the neurons in the olfactory bulb of ELA reared mice in response specifically to pleasant odorants. Additionally, in adult males only, we found altered recruitment of the reward system with changes in the functionning of the olfactory tubercle and ventral tegmental area, key structures involved in the odor hedonic coding. These results highlight potential impacts of ELA on network development and response to exogenous signals, diminishing interest in pleasant odorants with sex specificity. The current results point to ELA altering the neural substrates involved in olfactory sensory function and reward in males, with implications for understanding sensitivity or resilience for anhedonia and symptom severity in individuals at risk for depression associated with prior history of ELA.