Publication Record
Below you’ll find examples of research I’ve contributed to, published in various academic journals. Much of these are in-progress, so expect occasional updates.
Notes:
Coming soon!
Abstract:
We describe a novel role for dopamine in devaluing sensory memories of reward. Mesencephalic dopamine cells activated during a mediated devaluation phase were later chemogenetically reactivated. This retrieval of the devalued reward memory elicited a reduction in the hedonic evaluation of sucrose reward. Through optogenetic and chemogenetic manipulations, we confirm dopamine cells are both sufficient and necessary for mediated devaluation, and retrieval of these memories reflected dopamine release in the nucleus accumbens. Consistent with our computational modelling data, our findings indicate a critical role for dopamine in encoding predictive representations of the sensory features of reinforcement. Overall, we illuminate the elaborate nature of reinforcement signals encoded by dopamine and suggest novel approaches to treating a host of psychobiological disorders.
Notes:
While our lab was not the principle force behind this paper, the behavioral paradigms were adapted from our methods, and I played a role in training lab members using our equipment. The experiment makes use of several methods I’ve employed in my own work, including progressive-ratio behavioral tasks and qPCR for posthumous RNA quantification to check dopamine receptor expression.
Abstract:
Despite early-life disadvantage (ELD) in humans being a highly heterogenous construct, it consistently predicts negative neurobehavioral outcomes. The numerous environmental contributors and neural mechanisms underlying ELD remain unclear, though. We used a laboratory rat model to evaluate the effects of limited resources and/or heavy metal exposure on mothers and their adult male and female offspring. Dams and litters were chronically exposed to restricted (1-cm deep) or ample (4-cm deep) home cage bedding postpartum, with or without lead acetate (0.1%) in their drinking water from insemination through 1-week postweaning. Restricted-bedding mothers showed more pup-directed behaviors and behavioral fragmentation, while lead-exposed mothers showed more nestbuilding. Restricted bedding-raised male offspring showed higher anxiety and aggression. Either restricted bedding or lead exposure impaired goal-directed performance in a reinforcer devaluation task in females, whereas restricted bedding alone disrupted it in males. Lead exposure, but not limited bedding, also reduced sucrose reward sensitivity in a progressive ratio task in females. D1 and D2 receptor mRNA in the medial prefrontal cortex and nucleus accumbens (NAc) were each affected by the early-life treatments and differently between the sexes. Most notably, adult males (but not females) exposed to both early-life treatments had greatly increased D1 receptor mRNA in the NAc core. These results illuminate neural mechanisms through which ELD threatens neurobehavioral development and highlight forebrain dopamine as a factor.
Notes:
From performing optogenetic surgeries to running several behavioral paradigms, I was heavily involved in this series of experiments, often under the mentorship of at-the-time PhD student and now close friend Dr. Ben Fry. After our paper was selected to feature in Learning & Memory’s April 2021 issue, I was commissioned by my PI Dr. Alexander Johnson to design the cover art. L&M selected a fantastic title color palette to match.
Abstract:
The dopamine system has been implicated in decision-making particularly when associated with effortful behavior. We examined acute optogenetic stimulation of dopamine cells in the ventral tegmental area (VTA) as mice engaged in an effort-based decision-making task. Tyrosine hydroxylase-Cre mice were injected with Cre-dependent ChR2 or eYFP control virus in the VTA. While eYFP control mice showed effortful discounting, stimulation of dopamine cells in ChR2 mice disrupted effort-based decision-making by reducing choice toward the lever associated with a preferred outcome and greater effort. Surprisingly, disruptions in effortful discounting were observed in subsequent test sessions conducted in the absence of optogenetic stimulation, however during these sessions ChR2 mice displayed enhanced high choice responding across trial blocks. These findings suggest increases in VTA dopamine cell activity can disrupt effort-based decision-making in distinct ways dependent on the timing of optogenetic stimulation.