UCSF

Survival depends on the ability to adapt behaviors to constantly changing circumstances in order to achieve goals, such as obtaining food. The brain orchestrates flexible goal-directed behavior by integrating sensory inputs with memory and the current internal state. The frontal cortex is thought to be particularly important for this kind of integrative processing, and is also known to have relatively protracted maturation. Differences in adolescent behavior are often attributed to ongoing maturation of the frontal cortex. In Chapter 2, we developed behavioral assays to test behavioral flexibility at different developmental stages and test whether lesions of the dorsomedial prefrontal cortex (dmPFC) affect decision making. We found that juvenile mice were more flexible in a multiple choice foraging task compared to adults, and that performance at both ages was impaired by dmPFC lesions. We conclude that the dmPFC is "online" even at a young age, but perhaps operates differently. We next hypothesized that differences in frontal connectivity would relate to different decision-making patterns across development. It is unknown how frontal circuits mature at the cellular level, or if different sub-circuits may have different developmental trajectories. We leveraged advances in in vivo imaging technology to observe maturation of long range limbic connections to dmPFC from the orbitofrontal cortex (OFC) and basolateral amygdala (BLA) at the level of individual axons and pre-synaptic boutons. We found that axons in the juvenile brain were highly dynamic, and that different axon populations may follow unique developmental trajectories. Finally, we sought to understand how experience in the foraging task relates to plasticity of axons projecting from the OFC to dmPFC. We found that training on the multiple choice foraging task enhanced bouton dynamics compared to control groups. We further discovered that the density and experience-dependent gain of boutons was related to exploitation of a foraging rule, while exploration of alternatives was related to bouton loss. The magnitude of bouton gain or loss scaled with prediction errors estimated from individual choice histories. Taken together, the connectivity of the dmPFC may regulate the propensity for behavioral flexibility and exploration, and this connectivity is tuned by both development and experience.