1. Taste & the Gustatory System June 16, 2011

2. Brainstorming Why is taste important? Why did we develop a sense of taste? What do you think is the neurological basis of taste?

3. Mmm, Mmm Good. Chemicals in your food act on taste cells located in the taste buds of your tongue and mouth. 5 Basic Tastes –Bitter –Sweet –Sour –Salty –Umami Chandrashekar, J., M. A. Hoon, et al. (2006). "The receptors and cells for mammalian taste." Nature 444(7117): 288-294.

4. First Tastes Information processing begins in the taste cells. –Receptors are located on microvilli of the taste cells. Different tastes are represented by different receptor types. http://faculty.washington.edu/chudler/taste.html

5. Tasting Ions: Salty & Sour Sour –H+ in acids (like acetic acid in vinegar) Salty –Na+ from NaCl Entry of H+ or Na+ through the respective receptors opens ion channels and directly generates an electrical signal.

6. Sweet, Bitter, and Umami Involve G-Protein Coupled Receptors (GPCRs) –When a chemical binds to these receptors, they activate a G-protein, which causes a downstream chemical cascade. –A series of chemical events occurs that ultimately results in the opening or closing of ion channels. Sheridan, C. (2004). "A taste of the future." Nat Biotech 22(10): 1203-1205.

7. Sweet: –T1R2 and T1R3 receptors –Activates Ca2+ channels Umami: –T1R1 and T1R3 receptors –Activates Ca2+ channels Bitter: –T2R receptors interacting with gustducin Sweet, Bitter, and Umami

8. Taste Cell Summary Ion Channels –Sour: H+ –Salty: Na+ GPCRs –Sweet: T1R2 + T1R3 –Umami: T1R1 + T1R3 –Bitter: T2R Eisenstein, M. (2010). "Taste: More than meets the mouth." Nature 468(7327): S18-S19.

9. Buds to Brains Taste cells form synapses with axons from the facial, glossopharyngeal, and vagus cranial nerves. –Taste cells from each of the 3 regions of taste buds connects with a different nerve. Nucleus of the Solitary Tract in the medulla (NST) –Once again, topographical organization is at work—each of the 3 cranial nerves goes to a different portion of the NST. http://universe-review.ca/I10-85-taste.jpg

10. Neural Taste Processing NST projects to Ventral Posterior Medial Nucleus of the thalamus and continues to the cortices, amygdala, and hypothalamus http://faculty.washington.edu/chudler/taste.html

11. Tasty Visions Experiment

12. Class Discussion What Influences Taste? Sound Medicine: Neurobiology of Taste

13. Neurobiology of Eating What brain region controls eating? 1940, Hetherington & Ranson –Lesions of the ventromedial hypothalamus cause obesity & excess food intake in rats –Lesions of the lateral hypothalamus caused decreased eating & starvation https://wiki.brown.edu/confluence/display/BN0193S04/Historical+Background

14. What Does This Mean? Could the lateral hypothalamus be the brain’s control center for hunger, while the ventromedial hypothalamus is the center for satiety (feeling full) Oversimplified…there’s more to this story than that! –The brain & body have a host of chemicals to help induce hunger and satiety.

15. Gastrointestinal Peptides Ghrelin –Stimulates food intake & pre-meal hunger –Excess levels cause increased food intake & weight gain. Peptide YY –Inhibits food intake after meals Glucagon-like-peptide-1 –Inhibits food intake in response to nutrients in the gut Cholecystokinin (CCK) –Reduces food intake

16. Peripheral Hormones Leptin & Insulin –Both hormones reduce food intake. Both circulate in the body in response to fat content and enter the central nervous system in proportionate levels. –Receptors expressed in brain areas important for energy Leptin is a protein encoded for by the ob gene.

17. Leptin, Body Fat, & Food Douglas Coleman discovered in the 1960s that the ob genes indicates to the brain that fat reserves are at a normal level. So what would we expect from mice lacking the ob gene? In the 1990s, Jeffrey Friedman began studying leptin. –What happens if we give an ob/ob mouse leptin? –Reverses the obesity until normal levels of adipose tissue are reached.

18. Ob/Ob Mice http://en.wikipedia.org/wiki/Ob/ob_mouse

19. Energy homeostasis Schwartz et al Nature 2000 404:661

20. Central Food Signals Stimulate Food Intake (Orexigenic) –Neuropeptide Y (NPY) –Agouti-related protein (AgRP) Decrease Food Intake (Anorexigenic) –Melanocortins –Cocaine-& amphetamine- regulated transcript (CART) Barsh, G. S. and M. W. Schwartz (2002). "Genetic approaches to studying energy balance: perception and integration." Nat Rev Genet 3(8): 589-600.

21. Signaling Food Intake & Satiety To Stimulate Eating: –NPY is released from the Paraventricular nucleus, lateral hypothalamic, and prefornical areas. –Orexins and MCH from the prefornical areas and lateral hypothalamlus also play a role. To Reduce Eating: –  -MSH is derived from POMC in the paraventricular nucleus to stop eating. –Oxytocin, corticotrophin-releasing hormone, and thyrotrophin- releasing hormone may play roles as well. Schwartz, M. W., S. C. Woods, et al. (2000). "Central nervous system control of food intake." Nature 404(6778): 661- 671.

22. Other Factors Brain Stem Reward Pathways –Dopamine –Serotonin –Endocannabinoids –Opioids –Cholinergic systems

23. Summary

24. Who Knew Eating Was So Complicated?!? Schwartz, M. W., S. C. Woods, et al. (2000). "Central nervous system control of food intake." Nature 404(6778): 661-671.

25. Hypothalamus

26. Eating Disorder Treatment Plans http://fitnesslines.com/health-tips/what-is-an-eating- disordercausessymptoms-and-treatment-for-eating-disorders-in-children/

27. Smell Discrimination Experiment

28. What is Smell? Chemical molecules enter the nasal passage and are mixed with mucus in the olfactory epithelium. Olfactory hair cells respond to these chemicals and relay an electrical message to the brain. http://www.gunthersclass.com/lecture10p.html

29. Olfactory Receptors Another example of GPCRs –Allow Ca2+ & Na+ in, depolarizing the cell Firestein, 2001

30. Only expressed in select regions of the nasal cavity. A given receptor only maps to certain regions of the nasal passage. Where Are Sensory Neurons? From Lecture by Kerry Ressler, Emory University, 2006

32. Olfactory Bulb Olfactory information is processed in the olfactory bulb. –Consists of glomeruli: round regions without cell bodies that receive input from olfactory nerves. –Each neuron sends only 1 axon to 1 glomerulus in the olfactory bulb. Firestein 2001

33. Does This Organization Seem Familiar? From Lecture by Kerry Ressler, Emory University, 2006

34. Patterning Creates Scents The patterns of glomeruli that are stimulated is important for determining the odor sensed. From Lecture by Kerry Ressler, Emory University, 2006

35. Imaging techniques in anesthetized rats allow visualization of odor-induced activation of specific glomeruli Belluscio & Katz, 2001

36. Special Scent Processing Further processing occurs in the olfactory cortex, hippocampus, amygdala, and hypothalamus From Lecture by Kerry Ressler, Emory University, 2006

37. Changes in Smell NPR “Five Senses, Minus One: Living Without Smell” “The Dog Beneath the Skin”

38. Current Research in Taste and Smell