Early-Life Inflammation Affects Amygdala Function and Associated Behaviours in Adolescence and Adulthood
Date
2018-01-23
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Abstract
Inflammation is one of the most common results of viral and bacterial infections. While inflammation is a normal mechanism to clear pathogens, there is now emerging evidence that it can have profound effects on brain and behaviour. We discovered a susceptible window around postnatal day (P) 14, when a single exposure to an immune challenge with lipopolysaccharide (LPS - a bacterial, inflammatory compound) can cause changes in physiological and behavioural processes that persist into adulthood.
In this research, I addressed the hypothesis that a single postnatal immune challenge on P14 causes long lasting alterations in amygdala function and associated behaviours. I investigated reciprocal social behaviour, anxiety, startle and fear behaviour in both male and female rats, and found that an immune challenge on P14 decreased sociability and delayed the extinction of a fearful memory of a cue but not context. The effects of P14 LPS were present in both males and females. Acutely at P14, LPS activated cells in the amygdala and decreased concentrations of the endocannabinoid anandamide. In adolescence endocannabinoid concentration, receptor binding and degradative enzyme activity were altered in males and females. When the activity of the anandamide degrading enzyme FAAH was normalized by an inhibitor (oral or intra amygdala), before a social encounter, behavioural changes caused by P14 LPS were normalized to control levels. This lead us to believe that the amygdaloid cannabinoid system is a substantial contributor to changes seen in response to early-life inflammation. Early-life inflammation may substantially shape adolescent social and fear behaviour and contribute to related disorders. I further investigated amygdala-mediated schizophrenia-like behaviours and found that –unlike maternal immune activation- sensorimotor gating and reactions to stressors are unaffected by postnatal inflammation on P14. Lastly, I investigated alcohol drinking as another amygdala related behaviour and found that P14 LPS leads to increased alcohol drinking in the adult, when pre-exposed to alcohol during adolescence. Taken together, my work strongly suggests that inflammation on P14 alters amygdala signalling and behaviour, and could help us understand differences in susceptibility for fear and anxiety disorders, schizophrenia and alcohol disorders.
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Inflammation, Development, Brain, Mental Health
Citation
Doenni, V. M. (2018). Early-Life Inflammation Affects Amygdala Function and Associated Behaviours in Adolescence and Adulthood (Doctoral thesis, University of Calgary, Calgary, Canada). Retrieved from https://prism.ucalgary.ca. doi:10.11575/PRISM/5438