Lydia Nungesser
Project Year
Lydia beside her poster

When a stimulus is encountered, how we decide to interact with it depends on the context, known as context-dependent decision-making. However, this type of decision-making often goes awry in many psychiatric disorders such as schizophrenia, eating disorders, substance use disorder (SUD). Understanding the neural circuitry that underlies these disorders is crucial for the development of therapeutic treatments. The orbitofrontal cortex (OFC) is essential for the contextual regulation of reward predictions, yet the circuit mechanisms underlying this function remain unclear. Previously, we dissected the roles of a major OFC efferent pathway—projections to the central dorsal striatum (cDS)—in contextual regulation. Male and female rats performed a context-dependent discrimination task in which the reward-predictive status of two auditory target cues (X and Y) was determined by a visual contextual cue (A). Cue X was rewarded only in the presence of context A, and cue Y was rewarded only in the absence of context A (A:X+/X- /A:Y- / Y+). Using temporally precise optogenetic inhibition of OFC terminals, we found that silencing the OFC→cDS pathway profoundly disrupted the contextual regulation of reward seeking. Therefore, rats increased responding to nonrewarded cue/context configurations and decreased responding to rewarded configurations. Here, we use projection-specific fiber photometry in the OFC → cDS pathway to investigate how this pathway modulates contextual gating during our context-dependent discrimination task. Specifically, we examined the calcium dynamics within these projection neurons to reveal any correlation between neuronal activity and context discrimination behavior. Overall, we found that OFC→cDS projection neurons have phasic activity driven by the context: a decrease in activity during rewarded A:X+ trials, and an increase in activity during non-rewarded A:Y- trials. The weight of the context for cue X has a negative modulatory effect, yet a positive modulatory effect for Y. These findings propel us in the direction of better understanding the neural mechanisms that underlies context-dependent decision-making.

 

Major
Psychological and Brain Sciences
Faculty Sponsor(s):
Ron Keifling
Departments:
Psychological and Brain Sciences
Mentor(s):
Margo Le