Michael Krashes, Ph.D.
Section on Motivational Processes Underlying Appetite, Diabetes, Endocrinology, and Obesity Branch
Building 10, Room 5-5750
10 Center Drive
Bethesda, MD 20814
The ultimate goal of my research is to decipher the wiring diagram that underlies hunger. To achieve this, we employ novel genetic tools and techniques to dissect conserved feeding circuits with the hopes of furthering our understanding of the behaviors that drive humans to obtain food and ultimately how these behaviors can be manipulated to battle human eating afflictions.
The guiding mission of my laboratory is to research the inner workings of the mind. Specifically, we conduct studies that will help us understand how the rodent brain integrates peripheral senses, internal states, and experiences to orchestrate appropriate feeding behavior. The increased prevalence of obesity highlights the need for a more comprehensive dissection of the neural systems controlling food intake. This dissection should be one that extends beyond metabolic need and considers higher-order cognitive factors.
Nutrition is the primary requirement for all living systems; the essential survival value of feeding is the single most powerful agent in the evolution of a species. To satiate hunger and meet energy requirements, an animal must allocate resources to the detection (both external and internal) and memory of stimuli associated with the acquisition of food. Several studies have focused on a particular facet of feeding behavior: (1) the hypothalamic control of energy homeostasis, (2) the hedonic and rewarding aspects of food and the motivational component behind food procurement, or (3) the appetitive memory processes directed at learning food whereabouts. Despite the equivalence in the magnitude of these phases of food intake, their relative contributions have typically been investigated individually.
The long-term goal of my research is to bridge homeostatic satiety signals emanating from the hypothalamus with those higher-order cognitive factors and networks controlling food-seeking behavior using a combination of genetic and molecular tools to functionally unravel these circuit mechanisms. My research will investigate the neuromodulatory networks through which distinct subsets of hypothalamic neurons differentially influence specific downstream target cell types and synapses to guide both motivational behavior and learning and memory processing aimed at obtaining food.
Applying our Research
Obesity and eating disorders affect many of us. We can all relate to the subject of feeding, and the majority of us have struggled at one time or another with our weight or food control. The research performed in my laboratory will help deconstruct the brain circuits controlling hunger and help us understand how these complex neural networks drive feeding behavior, and ultimately how it relates to human health.
Need for Further Study
Deconvoluting the baroque nature of the circuits within the hypothalamus is paramount in comprehending their functional contribution to feeding behavior. The neural networks within this area of the brain are complex, thus it is necessary to use the latest neuroscience genetic tools and techniques to map the circuits underlying homeostatic behaviors such as feeding.
- Ph.D., University of Massachusetts Medical School, 2009
Burke CJ, Huetteroth W, Owald D, Perisse E, Krashes MJ, Das G, Gohl D, Silies M, Certel S, Waddell S. Layered reward signalling through octopamine and dopamine in Drosophila. Nature. 2012;492(7429):433-7.
Krashes MJ, DasGupta S, Vreede A, White B, Armstrong JD, Waddell S. A neural circuit mechanism integrating motivational state with memory expression in Drosophila. Cell. 2009;139(2):416-27.
Garfield AS, Li C, Madara JC, Shah BP, Webber E, Steger JS, Campbell JN, Gavrilova O, Lee CE, Olson DP, Elmquist JK, Tannous BA, Krashes MJ, Lowell BB. A neural basis for melanocortin-4 receptor-regulated appetite. Nat Neurosci. 2015;18(6):863-71.
Krashes MJ, Keene AC, Leung B, Armstrong JD, Waddell S. Sequential use of mushroom body neuron subsets during drosophila odor memory processing. Neuron. 2007;53(1):103-15.
Krashes MJ, Kravitz AV. Optogenetic and chemogenetic insights into the food addiction hypothesis. Front Behav Neurosci. 2014;8:57.