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Preclinical models of neurodevelopmental disorders typically use single inbred mouse strains, which fail to capture the genetic diversity and symptom heterogeneity that is common clinically. We tested whether modeling genetic background diversity in mouse genetic reference panels would recapitulate population and individual differences in responses to a syndromic mutation in the high-confidence autism risk gene, CHD8. We measured clinically relevant phenotypes in >1,000 mice from 33 strains, including brain and body weights and cognition, activity, anxiety, and social behaviors, using 5 behavioral assays: cued fear conditioning, open field tests in dark and bright light, direct social interaction, and social dominance. Trait disruptions mimicked those seen clinically, with robust strain and sex differences. Some strains exhibited large effect-size trait disruptions, sometimes in opposite directions, and-remarkably-others expressed resilience. Therefore, systematically introducing genetic diversity into models of neurodevelopmental disorders provides a better framework for discovering individual differences in symptom etiologies.
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Pavlovian occasion setting in human fear and appetitive conditioning: Effects of trait anxiety and trait depression
Contexts and discrete stimuli often hierarchically influence the association between a stimulus and outcome. This phenomenon, called occasion setting, is central to modulation-based Pavlovian learning. We conducted two experiments with humans in fear and appetitive conditioning paradigms, training stimuli in differential conditioning, feature-positive discriminations, and feature-negative discriminations. We also investigated the effects of trait anxiety and trait depression on these forms of learning. Results from both experiments showed that participants were able to successfully learn which stimuli predicted the electric shock and monetary reward outcomes. Additionally, as hypothesized, the stimuli trained as occasion setters had little-to-no effect on simple reinforced or non-reinforced stimuli, suggesting the former were indeed occasion setters. Lastly, in fear conditioning, trait anxiety was associated with increases in fear of occasion setter/conditional stimulus compounds; in appetitive conditioning, trait depression was associated with lower expectations of monetary reward for the trained negative occasion setting compound and transfer of the negative occasion setter to the simple reinforced stimulus. These results suggest that clinically anxious individuals may have enhanced fear of occasion setting compounds, and clinically depressed individuals may expect less reward with compounds involving the negative occasion setter.
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- Award ID(s):
- 1911441
- PAR ID:
- 10334959
- Date Published:
- Journal Name:
- Behaviour research and therapy
- Volume:
- 147
- ISSN:
- 0005-7967
- Page Range / eLocation ID:
- 103986
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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- Free Publicly Accessible Full Text
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Accepted Manuscript1.0
- Journal Article:
- https://doi.org/10.1016/j.brat.2021.103986
