The role of the medial prefrontal cortex in uncertainty based decision making in rats

Many behavioural patterns of humans and nonhuman animals could be framed as a problem of an agent deciding between various alternatives that have different outcomes. Since we live in a very complex environment these outcomes are usually soaked in uncertainty and ambiguity. It is therefore not surprising that many of us often make decisions that have bad consequences. Various psychiatric illnesses exacerbate this decision making problem, which leads to longer recovery times, poorer life quality and even death. Psychotropic drugs play a big role in mental disease treatment, but our understanding of why they work remains very superficial. Uncovering precise neural mechanisms underlying decision making processes has the potential to open up new venues for more targeted pharmacological treatments. Most antipsychotic and antidepressant drugs are based on processes that either stimulate or inhibit the flow of dopamine and serotonin. Midbrain areas that supply the brain with dopamine and serotonin are inter-connected to the subcortical and cortical areas of the brain, forming neural circuits that are involved in a wide range of behavioural patterns and moods. The dorsolateral prefrontal cortex and the anterior cingulate cortex contribute to the mechanism of top-down control of behaviour and are crucial in uncertainty based decision tasks. The medial prefrontal cortex in rats has been proposed as their functional and anatomical homologue. We have combined neural data, that was previously recorded from the medial prefrontal cortex in rats, with a behavioural model, to better understand what is the role of the medial prefrontal cortex in dynamic decision making. The data was recorded while the rats were deciding between a smaller immediate reward and a larger probabilistic reward. We used a reinforcement learning algorithm to model the probability of the rat choosing one option or the other. Additionally, we used data acquired from optogenetic stimulations to define neurons that project from the medial prefrontal cortex to the dorsal raphe nucleus and the ventral tegmental area. We found cells that correlate their firing rates with choice, outcome of choice and with the modelled probability of choosing one or the other arm. The majority of the projections cells were task responsive, with most of them correlating their firing rates with the probability variable. Our results indicate that the medial prefrontal cortex in rats contributes to maintaining behavioural strategies that maximize long-term outcomes and suggest that this could be achieved at least party via the frontal projections to the serotonergic and dopaminergic midbrain areas