UCSF

Flexible behavior in response to a changing environment is required for survival, and is the physical manifestation of communication among the prefrontal cortex and different subcortical systems. The basolateral amygdala (BLA), a crucial component of the reward circuitry mediating behavioral choices, is thought to encode the value of discrete cues in the environment. In particular, the BLA is thought to be required in updating the current cue-reward association. Previous studies have shown that the BLA is involved in flexible behavior, demonstrated using reversal learning tasks, where the subject has to inhibit responding to a previously rewarded cue and start responding to a previously unrewarded cue. However, the precise role of the BLA's contribution to inhibiting responding to a previously rewarded cue or learning to respond to a previously unrewarded cue remains unclear. Furthermore, it is not known if the BLA contributes to higher order rule learning that would occur over several reversals. Therefore, we examined the role of the BLA in a 4-choice odor discrimination reversal task across several reversal phases. We found that excitoxic lesions of the BLA impaired reversal learning compared to sham-lesioned mice. BLA-lesioned mice returned more frequently to the previously rewarded odor, indicating that the BLA primarily plays a role in inhibiting response to a previously rewarded cue instead of learning a new cue-reward association. Furthermore, since the BLA acts in concert with the prefrontal cortex to produce flexible behavior, understanding the dynamics of structural connectivity from the BLA to higher-order cortical regions involved in reversal learning is the first step to elucidate how amygdalocortical networks function. To develop our understanding of the development of these critical reward circuit connections, we used two-photon in vivo imaging to compare structural dynamics of axonal boutons of cortical-projecting BLA neurons in adult mice. We found that amygdala axons terminating in the dorsomedial prefrontal cortex are cortical-like in terms of their structural plasticity, and they are highly similar to orbitofrontal axons terminating in the same region. The work in this thesis elucidates a more precise role of the BLA in guiding flexible behavior, while also for the first time defining the baseline structural plasticity of axons from a limbic region projecting to a fronto-cortical region.