Dissecting the neural mechanisms of hedonic hunger and its effects on aging - Project Abstract Healthy aging may be a case of mind over matter. Experiments in systems ranging from worms to mice have established that neural states, which humans often associate with the feelings and motivations behind our behaviors, may be as influential as physical experiences in promoting a long and healthy life. One major motivational drive for animals is hunger, which promotes feeding. Feeding can be generated by the physiological need to consume nutrients as well as the hedonic properties of food. While brain circuits and mechanisms that regulate feeding have been described, it is unclear how they contribute to the generation of motive forces that drive feeding, and ultimately impact aging. Based on visually identified and quantified behaviors exhibited by hungry flies, we have found that flies exhibit distinct and measurable hunger drives that can be homeostatic (i.e., need-based) or hedonic (i.e., pleasure-based). These can be distinguished, at least in part, using sophisticated feeding behavior metrics that have shown homeostatic feeding is best represented by the number of feeding events on a protein rich food, while hedonic feeding is characterized by the duration of feeding events on a highly palatable food. We have discovered specific regions of the fly brain that influence feeding duration on palatable food but not the number of protein food events, suggesting that they are involved specifically in hedonic feeding. While the direct manipulation of homeostatic hunger has been shown to extend lifespan, preliminary data from our laboratory indicate that hedonic drive shortens fly lifespan. To understand how hedonic feeding is generated by the brain and manipulate this hedonic perception, we will determine how the identified hedonic neural circuitry encodes a hedonic hunger state in Aim 1. For Aim 2, we will identify how different levels of hedonic perception influences aging in Drosophila. The proposed study will provide key insight into how the brain weighs environmental cues to drive hedonic feeding behavior and how hedonic feeding impacts lifespan in various environmental contexts. Additionally, we will manipulate these cues to determine the cellular mechanisms through which feeding neural states can affect healthy aging.
