don’t we already know the molecular processes of learning and memory?

In the last two decades, we have come far in understanding the molecular mechanisms supporting neuronal function, including signaling cascades, epigenetic modifications, and changes in transcription. However, nearly all of this work has focused on a few brain areas that are not significantly involved in goal-directed learning, and in tasks which do not engage reward-guided choice. This is a problem, because there is strong evidence that these variables change the molecular sequelae of neuronal activation. We are interested in the transcriptional and translational signatures of reinforcement learning, how these depend on circuit-specific mechanisms, and how these differ across individuals on the basis of sex and genetics.

Essentially all neuropsychiatric diagnoses are biased by sex and gender in their presentation, etiology, and/or prognosis. In particular, neurodevelopmental disorders such as autism and attention-deficit/hyperactivity disorder are diagnosed far more often in boys than in girls. The reasons for this are complex, but significant evidence suggests that there are persistent gender differences in the presentation and manageability of neurodevelopmental conditions. This raises the possibility that sex differences significantly influence the mechanisms by which other factors, like genetics, tune the regions of the brain that regulate the reward-driven decision making and executive functions that seem to be most impacted. To understand this, however, we have to know how molecular factors function specifically in these regions, and how these might differ by sex and genetic status. Ultimately, this could reveal male-enriched mechanisms contributing to vulnerability, and/or female-enriched mechanisms contributing to resilience.

We are invested in understanding the molecular cascades in these regions which support operant learning, motivation, executive function, and the shift between habitual/automatic responses and goal-directed responses. Utilizing optogenetic and chemogenetic approaches, we can further examine how these cascades relate to neuronal conditions which predispose to goal-directed responses versus those that inhibit goal-directed responding, driving impulsive, compulsive, or habitual behaviors instead.


Recent data from our lab suggests that there are patterns of gene expression which distinguish learning from performance or reward in multiple key brain areas, and that these patterns may be sex-specific.