How does decision making go awry in addiction? Decision making processes have been extensively studied in humans, primates, and rodents. However, we still do not fully understand the neurophysiological processes supporting decision making. In order to answer how decision making goes awry, we must first ask how we make decisions. Maladaptive decision making could result from an error in processing in one or several decision making systems or a conflict between different decision making systems. Consequently, we need to establish a better understanding of the mechanisms of deliberative decision making in order to understand the neurological causes of maladaptive decision making. I propose to utilize a novel viral technology (DREADD) to examine how three neural systems integrate information during deliberative decision making. I propose to examine how the ventral striatum evaluates reward, how the hippocampus imagines the future, how the prefrontal cortex biases hippocampal representations of context, and finally how these three systems interact/bias each other during deliberative decision making. I propose to simultaneously record neuronal ensembles and local field potentials from the prefrontal cortex, hippocampus and ventral striatum in rats trained on a spatial neuroeconomic task (Restaurant Row). On the Restaurant Row task rats are presented with the option of different food rewards dispensed after variable random delays. The rats have the choice of waiting out the delay for the food reward or skipping the choice and moving on to the next reward site. Combining large ensemble recordings with sophisticated computational analyses permits us to measure neural processes at incredibly fast time-scales (ms vs. minutes and hours). By doing so we can better analyze neural processes at time-scales more analogous to the temporal specificity that characterizes information processing seen during decision-making (Johnson et al., 2009). Therefore, we can extrapolate abstract cognitive processes, such as decision-making, from concrete neurobiological processes. This proposal aims to examine three questions: 1) what are the effects of silencing the prefrontal cortex on behavioral correlates of the dynamic search and evaluation processes (VTE) seen during decision-making, 2) is there a causal relationship between PFC and hippocampal spatial representations of prediction/planning and/or ventral striatum covert expectations of reward, 3) does silencing the prefrontal cortex impair off-line coordinated hippocampal-ventral striatal place-reward reactivation (replay). By answering these questions we will have a better understanding of how these disparate neural systems interact during deliberative decision making and get closer to answer the question: how does decision making go awry in addiction?
We need to establish a better understanding of the mechanisms of deliberative decision making in order to understand the neurological causes of maladaptive decision making seen in addiction. Studying how different neural systems interact during deliberative decision-making would provide critical contribution to theoretical conceptions of dysfunctional decision-making processes and help conceive appropriate therapeutic and pharmacological interventions for addiction.
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