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Ongoing (M58)
Neural mechanisms underlying stress eating: The role of dopamine-sensitive prefrontal cortex circuits in stress-altered pursuit of rewarding food
FunderNetherlands Organisation for Scientific Research (NWO)
Duration20 Jan 2022 - 31 Dec 9999
Project codeVI.Vidi.203.102
Open Access mandatePublications: NoResearch data: No
Identifiers
Project timeline0.1%
Description
Stress can enhance cravings for palatable food (e.g. fat and sugar) and drive impulsive food seeking. In vulnerable individuals these effects contribute to binge eating and obesity. The neurobiology underlying stress eating remains largely unclear. This proposal aims to elucidate how stress alters neural circuit function to increase the pursuit of palatable foods and assesses how this can be counteracted. The project focuses on the prefrontal cortex (PFC): a stress-sensitive region critical in selecting behavioral strategies. Stressors drive surges of dopamine in PFC, where neuronal subsets express various dopamine receptors. Amongst these are PFC subsets innervating basolateral amygdala (BLA) and nucleus accumbens (NAc), with roles in food craving and impulse control. However, it is unresolved if/how these PFC pathways mediate stress eating. This proposal addresses this using mouse models. Aim 1 examines if stress strengthens PFC-BLA and weakens PFC-NAc connectivity [ex vivo]. I will elucidate the consequences of stress on specific synapses from dopamine-sensitive PFC neurons onto BLA and NAc neurons. To this end I will combine light-driven stimulation of specific parallel PFC pathways with electrophysiological measures of distinct BLA and NAc cell types in brain slices. I will also unravel the induction and expression mechanisms behind stress-driven plasticity. Aim 2 determines if PFC-BLA and PFC-NAc activity is linked to stress-driven bingeing and impulsivity [in vivo[. I will perform single-cell calcium recordings of PFC-NAc and PFC-BLA output pathways (miniature microscopy) and their dopamine input signals (fiber photometry) during stress-driven bingeing and impulsive food seeking. I will also use in vivo (chemogenetic) circuit manipulations to counteract stress-induced changes in PFC pathways, and assess the impact of this on the risk to develop obesity. Overall this study would provide key insights in how stress affects neural systems involved in impulsivity and food choices, and would address how this confers risk for obesity.
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Stress can enhance cravings for palatable food (e.g. fat and sugar) and drive impulsive food seeking. In vulnerable individuals these effects contribute to binge eating and obesity. The neurobiology underlying stress eating remains largely unclear. This proposal aims to elucidate how stress alters neural circuit function to increase the pursuit of palatable foods and assesses how this can be counteracted. The project focuses on the prefrontal cortex (PFC): a stress-sensitive region critical in selecting behavioral strategies. Stressors drive surges of dopamine in PFC, where neuronal subsets express various dopamine receptors. Amongst these are PFC subsets innervating basolateral amygdala (BLA) and nucleus accumbens (NAc), with roles in food craving and impulse control. However, it is unresolved if/how these PFC pathways mediate stress eating. This proposal addresses this using mouse models. Aim 1 examines if stress strengthens PFC-BLA and weakens PFC-NAc connectivity [ex vivo]. I will elucidate the consequences of stress on specific synapses from dopamine-sensitive PFC neurons onto BLA and NAc neurons. To this end I will combine light-driven stimulation of specific parallel PFC pathways with electrophysiological measures of distinct BLA and NAc cell types in brain slices. I will also unravel the induction and expression mechanisms behind stress-driven plasticity. Aim 2 determines if PFC-BLA and PFC-NAc activity is linked to stress-driven bingeing and impulsivity [in vivo[. I will perform single-cell calcium recordings of PFC-NAc and PFC-BLA output pathways (miniature microscopy) and their dopamine input signals (fiber photometry) during stress-driven bingeing and impulsive food seeking. I will also use in vivo (chemogenetic) circuit manipulations to counteract stress-induced changes in PFC pathways, and assess the impact of this on the risk to develop obesity. Overall this study would provide key insights in how stress affects neural systems involved in impulsivity and food choices, and would address how this confers risk for obesity.
