title: Obesity-Induced Structural and Neuronal Plasticity in the Lateral Orbitofrontal Cortex.
abstract: 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.
authors.affiliation: Department of Anesthesiology, Pharmacology and Therapeutics, University of British Columbia, Vancouver, British Columbia, Canada.|Hotchkiss Brain Institute, University of Calgary, Calgary, Alberta, Canada.
authors.forename: Jennifer L
authors.initials: JL
authors.lastname: Thompson
authors.affiliation: Hotchkiss Brain Institute, University of Calgary, Calgary, Alberta, Canada.
authors.forename: Michael
authors.initials: M
authors.lastname: Drysdale
authors.affiliation: Department of Anesthesiology, Pharmacology and Therapeutics, University of British Columbia, Vancouver, British Columbia, Canada.|Hotchkiss Brain Institute, University of Calgary, Calgary, Alberta, Canada.
authors.forename: Corey
authors.initials: C
authors.lastname: Baimel
authors.affiliation: Hotchkiss Brain Institute, University of Calgary, Calgary, Alberta, Canada.
authors.forename: Manpreet
authors.initials: M
authors.lastname: Kaur
authors.affiliation: Hotchkiss Brain Institute, University of Calgary, Calgary, Alberta, Canada.
authors.forename: Taigan
authors.initials: T
authors.lastname: MacGowan
authors.affiliation: Department of Anesthesiology, Pharmacology and Therapeutics, University of British Columbia, Vancouver, British Columbia, Canada.|Hotchkiss Brain Institute, University of Calgary, Calgary, Alberta, Canada.
authors.forename: Kimberley A
authors.initials: KA
authors.lastname: Pitman
authors.affiliation: Hotchkiss Brain Institute, University of Calgary, Calgary, Alberta, Canada.
authors.forename: Stephanie L
authors.identifier: http://orcid.org/0000-0001-7546-5687
authors.initials: SL
authors.lastname: Borgland
mesh_terms: D000818:Animals; D059305:Diet, High-Fat / Q000009:adverse effects*; D002149:Energy Intake / Q000502:physiology; D008297:Male; D009473:Neuronal Plasticity / Q000502:physiology*; D009765:Obesity / Q000150:complications / Q000473:pathology* / Q000503:physiopathology; D009924:Organ Culture Techniques; D017397:Prefrontal Cortex / Q000473:pathology* / Q000503:physiopathology; D017966:Pyramidal Cells / Q000502:physiology; D051381:Rats; D020318:Rats, Long-Evans