Obesity-induced structural and neuronal plasticity in the lateral orbitofrontal cortex

The orbitofrontal cortex (OFC) integrates sensory information with the current value of foods and updates actions based on this information. Obese humans and rats fed a cafeteria diet have impaired devaluation of food rewards, implicating a potential obesity-induced dysfunction of the OFC. We hypothesized that obesity alters OFC pyramidal neuronal structure and function and reduces conditioned suppression of feeding. Rats were given restricted (1 h/day), extended (23 h/day) or no (chow only) access to a cafeteria diet and tested for a conditioned suppression of feeding. Golgi-cox impregnation and whole-cell patch clamp experiments were performed in lateral OFC pyramidal neurons of rats from the 3 feeding groups. Rats with 40 days of extended, but not restricted, access to a cafeteria diet became obese and continued to feed during foot shock-predicting cues. Access to a cafeteria diet induced morphological changes in basilar dendrites of lateral OFC pyramidal neurons. While there were no alterations in excitatory synaptic transmission underlying altered spine density, we observed a more depolarized resting membrane potential. This was accompanied by decreased inhibitory synaptic transmission onto lateral OFC pyramidal neurons due to decreased release probability at GABAergic inputs. These changes could underlie the inability of the OFC to encode changes in the motivation value of food that is observed in obese rodents and humans.