Uncertainty in development changes responses to uncertainty in adulthood: a study of developmental food insecurity and decision making in mice

• In Event: How experiencing uncertainty shapes the development of learning and decision-making

Abstract

A major challenge for neuroscience, public health, and evolutionary biology is to understand the effects of scarcity and uncertainty on the developing brain. Currently, a significant fraction of children and adolescents worldwide experience insecure access to food. The goal of our project was to test in mice if transient experience of insecure versus secure access to food during the juvenile-adolescent period produced lasting differences in learning, decision making, and dopamine system in adulthood. We manipulated feeding schedule in mice from postnatal day(P) 21 to 40 as food insecure or ab libitum and found that when tested in adulthood (after P60), males with different developmental feeding history showed significant differences in multiple metrics of cognitive flexibility in learning and decision making. Adult females with different developmental feeding history showed no differences in cognitive flexibility, but did show significant differences in adult weight. We next applied reinforcement learning models to these behavioral data. The best fit models suggested that in males, developmental feeding history altered how mice updated their behavior after negative outcomes. This effect was sensitive to task context and reward contingency. Notably, the group that experienced food insecurity in development showed greater flexibility than their ad libitum fed siblings, when tested in adulthood under conditions with greater uncertainty. However under other conditions mice with a history of food insecurity mice were significantly less flexible than their always ad libitum fed siblings. In neurobiological experiments in males, we found that the two feeding history groups showed significant differences in AMPAR/NMDAR ratio of excitatory synapses on nucleus accumbens-projecting midbrain dopamine neurons and evoked dopamine release in dorsal striatal targets. Together, these data show in a rodent model that transient differences in feeding history in the juvenile-adolescent period can have significant impacts on adult weight, learning, and decision making. We will discuss the interpretation of these results from a public health and adaptive developmental plasticity perspective.

Author

• Linda Wilbrecht, UC Berkeley
  Presenting Author