GABA-Mediated Inactivation of Medial Prefrontal and Agranular Insular Cortex in the Rat: Contrasting Effects on Hunger- and Palatability-Driven Feeding

Abstract

A microanalysis of hunger-driven and palatability-driven feeding was carried out after muscimol-mediated inactivation of two frontal regions in rats, the agranular/dysgranular insular cortex (AIC) and the ventromedial prefrontal cortex (vmPFC). Food and water intake, feeding microstructure, and general motor activity were measured under two motivational conditions: food-deprived rats given standard chow or ad libitum-fed rats given a palatable chocolate shake. Muscimol infusions into the AIC diminished intake, total feeding duration, and average feeding bout duration for the palatable-food condition only but failed to alter exploratory-like behavior (ambulation or rearing). In contrast, intra-vmPFC muscimol infusions did not alter the overall intake of chow or chocolate shake. However, these infusions markedly increased mean feeding bout duration for both food types and produced a modest but significant reduction of exploratory-like behavior. The lengthening of feeding-bout duration and reduction in rearing were mimicked by intra-vmPFC blockade of AMPA-type but not NMDA-type glutamate receptors. Neither water consumption nor the microstructure of water drinking was affected by inactivation of either site. These results indicate a regional heterogeneity in frontal control of feeding behavior. Neural processing in AIC supports palatability-driven feeding but is not necessary for intake of a standard food under a food-restriction condition, whereas ventromedial prefrontal cortex, and AMPA signaling therein, modulates the duration of individual feeding bouts regardless of motivational context. Results are discussed in the context of regionally heterogeneous frontal modulation of two distinct components of feeding behavior: reward valuation based upon taste perception (AIC) vs switching between ingestive and non-ingestive (eg, exploratory-like) behavioral repertoires (vmPFC).

Feeding-modulatory effects of mu-opioids in the medial prefrontal cortex: a review of recent findings and comparison to opioid actions in the nucleus accumbens

“…μ-OR stimulation in the ventromedial prefrontal cortex (vmPFC), mainly the infralimbic region, engenders feeding both in food-deprived and ad libitum -maintained rats (Mena et al 2011); the organization of this feeding response consists of brief feeding bouts, and abrupt switching between food-directed responses and responses directed away from food (e.g., ‘exploratory-like’ ambulatory or rearing behaviors). This pattern is essentially the opposite of that engendered by GABA-mediated inactivation of the vmPFC (i.e., longer feeding bouts and less ambulation and rearing) (Baldo et al 2016; Mena et al 2011), suggesting that the net behaviorally relevant effect of μ-OR stimulation is to activate or disinhibit cortical output. Presently, the role of μ-ORs in regulating pyramidal neuron activity (and thus cortical output) is not well understood.…”

Differential mesocorticolimbic responses to palatable food in binge eating prone and binge eating resistant female rats

“…If so, then enhanced neurotransmission, either in the amount of neurotransmitter released or receptor signaling, could underlie the more extensive activation of NA neurons in BEP than in BER rats. Within the mPFC, complex interactions between GABAergic interneurons and glutamatergic projection neurons mediate executive control of goal-directed behaviors, including the amount and microstructure of chow and PF consumption [8,28–32]. In mice, PF induces differential Fos expression in inhibitory and excitatory mPFC neurons; the vast majority of excitatory projection neurons are activated by PF, whereas only a small subset of inhibitory interneurons is activated by PF [8].…”

A molecularly defined insular cortex --> central amygdala circuit mediates conditioned overconsumption of food

“…), nor did it affect food intake after refeeding ( Fig 1C; Post-fast Feeding, n.s.). Inhibition of the projection neurons in the insular cortex also had no effect on anxiety behavior in an elevated plus maze task or 15 general locomotor activity ( Figure 1D-E, n.s.). These results indicate that glutamatergic projection neurons in the insular cortex mediate conditioned overconsumption, but do not regulate homeostatic feeding (14,15).…”

“…We found that returning these mice to this same environment at a later time led to increased food consumption relative to controls even when the mice were fed. The data indicated that the mice had associated the cues in this environment with a prior experience of hunger (and food availability) leading the mice to 15 continue to eat even when they were satiated. Thus mice previously given food in a novel context when hungry (Ctx+) ate more food when returned to this environment than control mice (Ctx-) even when they were satiated ( Fig.…”

“…One Sentence Summary: Nitric oxide synthase-1 neurons in the insular cortex promote overconsumption by projecting to the central amygdala to suppress a homeostatic satiety signal. 15 20 25 3 Main Text: Increased food consumption leading to obesity now affects more than 30% of Americans, a public health crisis costing in excess of $150 billion per year (1)(2). Feeding is a complex motivated behavior that is coordinated by homeostatic (e.g.…”