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 © 2016 Macmillan Publishers Limited. All rights reserved. 3pyramidal 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. Golgicox 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.

Disinhibition of the orbitofrontal cortex biases decision making in obesity

“…To test this, we isolated and quantified miniature inhibitory postsynaptic currents (mIPSCs) onto lOFC pyramidal neurons. The frequency, but not the amplitude of mIPSCs were decreased in obese relative to lean mice in lOFC pyramidal neurons (Figure 4f-h) , suggesting a decrease in presynaptic GABA release and consistent with previous findings from our lab 22 . Thus, diet-induced obesity reduces inhibitory drive onto lOFC pyramidal neurons leading to increased excitability.…”

“…GABAergic release probability onto lOFC pyramidal neurons was reduced in obese mice. This is consistent with previous work showing that obese rats with 24h access to a cafeteria diet had reduced GABAergic release probability onto layer II/III pyramidal neurons in the lOFC 22 . Obese mice, from 3 different cohorts, also demonstrated enhanced excitability of pyramidal neurons.…”

“…We propose the enhanced excitability of lOFC pyramidal neurons is due to disinhibition rather than a change in intrinsic excitability. First, previous work demonstrated that the excitability of lOFC pyramidal neurons from obese rats is not changed in the presence of synaptic blockers 22 . Secondly, the GABA A receptor antagonist, picrotoxin, restored excitability of lOFC neurons from obese mice to that of lean mice, without significantly altering the excitability of pyramidal neurons of lean mice.…”

Neuroanatomical correlates of food addiction symptoms and body mass index in the general population

“…First evidence suggests that individual differences in OFC thickness partly mediate the genetic risk for obesity (Opel et al, 2017), possibly by provoking, or failing to inhibit, impulsive and compulsive (eating) behavior. Subsequent intake of high fat diet, weight gain and adverse metabolic consequences of obesity, such as increased low-grade inflammation or progressive insulin resistance, might further harm brain tissue (Corlier et al, 2018;Dingess, Darling, Kurt Dolence, Culver, & Brown, 2017;Shaw, Nettersheim, Sachdev, Anstey, & Cherbuin, 2017;Thompson et al, 2017). In this vicious cycle, structural damage to frontal brain regions would contribute to more impulsive and compulsive eating behavior, and lead to even more weight gain or reduced dieting success (DelParigi et al, 2007;Schmidt et al, 2018).…”

Neuroanatomical correlates of food addiction and obesity in the general population

“…Meanwhile, we find strong evidence for an association of BMI and lower cortical thickness in the OFC which might result from the adverse metabolic consequences of obesity (Cazettes et al, 2011;Dingess et al, 2017), and thus not be causally related to food addiction (Marqués-Iturria et al, 2013;Kharabian Masouleh et al, 2016;Thompson et al, 2017). Obesity, and especially visceral fat accumulation, is known to coincide with adverse metabolic responses, such as increased low-grade inflammation or progressive insulin resistance (Van Gaal et al, 2006), that enhance the vulnerability of the brain tissue (Corlier et al, 2018).…”