Behavioral (feeding) and systems (energy balance, thermoregulation, autonomic) neuroscience; neural bases of obesity and anorexia, neural basis of reward, motivation and emotion
The dramatic increase in the prevalence of obese and overweight individuals has intensified interest in obesity as a disease with significant health consequences and co-morbidities (e.g., type 2 diabetes, cardiovascular disease, cancer). Obesity, like hypertension, diabetes, and bipolar disorder, is a chronic disease that requires chronic treatment. As caloric restriction [dieting reduces weight but also alters physiology that favors weight regain] is ineffective and surgery has serious side effects, the development of effective pharmacotherapies is critical. Drug targets rely on findings from basic research on the neurobiology of energy balance. Our lab is focused on defining the neural circuits, neurochemical systems, and intracellular signaling pathways that contribute to the control of food intake, food reward and associative control on feeding. Unique to our approach is the perspective that the neural control of energy balance is anatomically distributed rather than centered in any one region of the brain. This perspective leads us to examine the neural processing of peripherally generated neural signals (e.g., vagal afferent response to ingested food) and blood-born correlates of energy status signals (e.g., leptin, ghrelin) that act at multiple brain nuclei including but not limited to the caudal brainstem (e.g. NTS, PBN), midbrain (e.g. ventral tegmental area), hypothalamus, thalamus, hippocampus, nucleus accumbens, prefrontal cortex. Also influencing our work is the idea that the environmental factors that drive feeding behavior such as context, and learning as well as food palatability and its impact on reward are extremely important in understanding the control of feeding behavior, and like satiation and energy status signals, are also not controlled by distinct and unique neural circuits. Rather, our perspective is that each of these factors may involve signaling in anatomically distributed nuclei, and each nucleus may be involved in several functional controls of feeding.
Professor Harvey Grill will not be accepting new graduate students for admission for Fall 2019.
Alhadeff AL, Holland RA, Nelson A, Grill HJ, De Jonghe BC.. Glutamate receptors in the central nucleus of the amygdala mediate cisplatin-induced malaise and energy balance dysregulation through direct hindbrain projections. J Neuroscience. 2015 Aug 5;35(31):11094-104.
Alhadeff, A.L., Grill, H.J. Hindbrain glucagon-like peptide-1 receptor signaling reduces appetitive and motivational aspects of feeding. Am J. Physiology, 2014, Aug 15;307(4):R465-70.
Kanoski, S.E., Fortin, S.M., Ricks, K.M., Grill, H.J. Ghrelin signaling in the ventral hippocampus stimulates learned and motivational aspects of feeding via PI3K-Akt signaling
Biological Psychiatry, 2013 May 1;73(9):915-23.
Grill, H. J., M.R. Hayes. Hindbrain neurons are an essential hub in the neuroanatomically distributed control of energy balance. Cell Metabolism 2012 Sep 5;16(3):296-309. Review
Kanoski SE, Zhao S, Guarnieri DJ, DiLeone RJ, Yan J, De Jonghe BC, Bence KK, Hayes MR, Grill HJ. Endogenous leptin receptor signaling in the medial nucleus tractus solitarius affects meal size and potentiates intestinal satiation signals. Am J Physiol Endocrinol Metab. 2012 Aug 15;303(4):E496-503
Kanoski SE, Fortin SM, Arnold M, Grill HJ*, Hayes MR*. Peripheral and central GLP-1 receptor populations mediate the anorectic effects of peripherally administered GLP-1 receptor agonists, Liraglutide and Exendin-4. Endocrinology. 2011 Aug;152(8):3103-12
Hayes MR, Leichner TM, Zhao S, Lee GS, Chowansky A, Zimmer D, De Jonghe BC, Kanoski SE, Grill HJ*, Bence KK*. Intracellular signals mediating the food intake-suppressive effects of hindbrain glucagon-like peptide-1 receptor activation. Cell Metabolism 2011 Mar 2;13(3):320-30
Skibicka KP, Alhadeff AL, Leichner TM, Grill HJ. Neural controls of prostaglandin 2 pyrogenic, tachycardic, and anorexic actions are anatomically distributed. Endocrinology. 2011 Jun;152(6):2400-8.
Kanoski SE, Hayes MR, Greenwald HS, Fortin SM, Gianessi CA, Gilbert JR, Grill HJ. Hippocampal leptin signaling reduces food intake and modulates food-related memory processing. Neuropsychopharmocology, 2011, Aug;36(9):1859-70.
Hayes MR, Kanoski SE, Alhadeff AL, Grill HJ. Comparative Effects of the Long-Acting GLP-1 Receptor Ligands, Liraglutide and Exendin-4, on Food Intake and Body Weight Suppression in Rats. Obesity . Jul;19(7):1342-9. 2011 Mar 17.
Grill. H.J. Leptin and the systems neuroscience of meal size control. Frontiers in Neuroendocrinology, 2010 Jan;31(1):61-78