A neuronal population code for resemblance between drug and nondrug reward outcomes in the orbitofrontal cortex

The orbitofrontal cortex (OFC) is implicated in choice and decision-making in both human and non-human animals. We previously identified in the rat OFC a mechanism that influences individual drug choices and preferences between a drug and a nondrug (i.e., sweet) outcome that is common across different types of drugs (cocaine and heroin). Importantly, this research also revealed some intriguing drug-specific differences. Notably, the size of non-selective OFC neurons that indiscriminately encode both the drug and the sweet outcomes varies as a function of the drug outcome available (cocaine or heroin). Here we tested the hypothesis that the relative size of the non-selective OFC population somehow represents the degree of resemblance between the drug and nondrug reward outcomes. We recorded OFC neuronal activity in vivo in the same individual rats while they were choosing between two outcomes with varying degrees of resemblance: high (two concentrations of sweet), intermediate (sweet versus heroin) and low (sweet versus cocaine). We found that the percentage of non-selective OFC neurons dramatically increased with the degree of resemblance between choice outcomes, from 26 to 62%. Overall, these findings reveal the existence of a neuronal population code for resemblance between different kinds of choice outcomes in the OFC.