The Role of the Rat Prefrontal Cortex and Sex Differences in Decision-Making

The prefrontal cortex is critical for decision-making across species, with its activity linked to choosing between options. Drift Diffusion Models (DDMs) are commonly employed to understand the neural computations underlying this behavior. Studies exploring the specific roles of regions of the rodent prefrontal cortex in controlling the decision process are limited. This study explored the role of the prelimbic cortex (PLC) in decision-making using a two-alternative forced-choice task. Rats first learned to report the location of a lateralized visual stimulus. The brightness of the stimulus indicated its reward value. Then, the rats learned to make choices between pairs of stimuli. Sex differences in learning were observed, with females responding faster and more selectively to high-value stimuli than males. DDM analysis found that males had decreased decision thresholds during initial learning, whereas females maintained a consistently higher drift rate. Pharmacological manipulations revealed that PLC inactivation reduced the decision threshold for all rats, indicating that less information was needed to make a choice in the absence of normal PLC processing. Mu opioid receptor stimulation of the PLC had the opposite effect, raising the decision threshold and reducing bias in the decision process towards high-value stimuli. These effects were observed without any impact on the rats’ choice preferences. Our findings suggest that PLC has an inhibitory role in the decision process and regulates the amount of evidence that is required to make a choice. That is, PLC activity controls “when”, but not “how”, to act. Significance Statement This study reports causal evidence for a part of the rat prefrontal cortex, the prelimbic cortex, in controlling the amount of information needed to make a choice. Results were based on reversible inactivation using the GABA-A agonist muscimol and by stimulation of mu opioid receptors using intra-cortical infusions of the selective mu agonist DAMGO. We also found evidence for a sex difference in learning and performing a visually guided two-alternative forced-choice task. Drift Diffusion Models found that females had stable decision processes throughout learning, and showed a persistent bias against the lower value option. By contrast, males exhibited changes in their decision processes, notably reducing the amount of information needed to make choice over the period of early choice learning.