Grant: Discovery Grants Program - Individual

To make adaptive decisions in a ever-changing world, information about the past must be brought to bear on the present decision. Actions that lead to reward are likely to be repeated, while those leading to punishment are not. A specific frontal brain region, the medial prefrontal cortex (mPFC), appears critical to this process. For example, humans with mPFC damage show poor judgement in decisions involving risk. In rats, the homologous region plays a critical role in retrieval of memories. I hypothesize that the role of the mPFC in both humans and rats is to guide decisions by predicting the emotional consequences of contemplated actions, using past experience as a guide. To test this hypothesis, I will use multi-electrode recording (in which tiny wires are used to record spiking activity from dozens of neurons simultaneously) and temporary inactivation (involving local injections of anesthetics) to study decision making in rats. The first group of experiments seek to uncover how reward and fear are represented by neurons in mPFC. Are the same set of neurons used to code both positive and negative experiences? Experiments will also look at the influence of mitigating factors, such as control over noxious stimuli or effort needed to achieve reward, on the neural coding of noxious or rewarding stimuli. A second group of experiments explores the role of mPFC in memory retrieval. They seek to clarify whether mPFC mediates short-term memory in addition to its well documented role in long-term memory. A final group of experiments seeks direct evidence that mPFC guides decisions by predicting emotional responses to planned actions. One experiment involves switching the stimuli which lead to reward from one dimension to another. A second uses a gambling task involving a choice between a high-risk, high reward option and a safer, lower reward option. In both cases, I expect to see neural activity directly related to the anticipated emotional outcome of individual choices. This research seeks a mechanistic understanding of the role of mPFC in decision making in both rats and humans and will further our understanding of the many mental disorders tied to mPFC dysfunction including addiction, schizophrenia and depression.