Neuromodulators of orbitofrontal cortex function: A review of endocannabinoid, neurotrophin, and cell adhesion systems

The ability to incorporate changing information from the environment into our actions is essential for flexible behavior. The orbitofrontal cortex (OFC) is involved in integrating new information into on-going and future actions. As elsewhere in the brain, neuronal activity in the OFC is subject to fine-tuning by neurotransmitters like serotonin, dopamine, and norepinephrine. The purpose of this review is to highlight other neuromodulatory factors that have received less attention but are also potent regulators of OFC-dependent decision making. Specifically, we summarize the impacts of endocannabinoids, the neurotrophin Brain-derived Neurotrophic Factor, and cell adhesion systems in both medial and lateral compartments of the OFC. Generally speaking, perturbations to these systems disrupt flexible decision making, resulting in behaviors resembling poor learning, perseveration, and deferral to habitual actions. Understanding the molecular mechanisms supporting OFC function may drive the discovery of novel therapeutic approaches to alleviating these symptoms in various neuropsychiatric disorders.