How do animals sense the environment
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1. The document describes a lecture on how animals sense their environment through sensory systems like olfaction. 2. It discusses the mechanism of olfactory sensation in olfactory sensory neurons, including how odorant molecules bind receptors in cilia to activate downstream signaling cascades, generating receptor potentials and action potentials. 3. The summary highlights experiments in C. elegans that screen mutant worms to identify genes important for sensory neuron development and function based on abnormal dye-filling of ciliated sensory neurons.
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How do animals sense the environment
- 1. BIOL 3520: Cell Physiology 1 Lecture 25: How do animals sense their environment? Tiffany A. Timbers, Ph.D. http://www.slideshare.net/ttimbers/how-do-animals-sense-the-environment
- 5. Learning Objectives You will be able to: • Describe the mechanism for sensation in olfactory sensory neurons. • Describe how the components of cilia contribute to sensation. • Name 3 major systems affected in patients with cilia disorders. • Interpret results from an experiment with regards to a given hypothesis about sensation. 5
- 7. Cell Physiology Source Book, 4th Edition Chapter 36, p. 633-646 - Sensory Receptors and Mechanotransduction Chapter 38, p. 669-678 - Visual Transduction Chapter 39, p. 690-695 - Gustatory and Olfactory Sensory Transduction Assigned Readings: 7
- 8. Reminder: Action Potential Generation extracellular intracellular Na+ Ca2+ Na+ Na+ Na+ Ca2+ Ca2+Ca2+ Na+ Na+ Ca2+ Na+ Resting state 8
- 9. Reminder: Action Potential Generation extracellular intracellular Na+ Ca2+ Na+ Na+ Na+ Ca2+ Ca2+ Ca2+ Na+ Na+ Ca2+ Na+ Na+ Ca2+ Na+ Ca2+ Na+ Ca2+ Depolarization 9
- 10. Reminder: Action Potential Generation extracellular intracellular Na+ Ca2+ Na+ Na+ Na+ Ca2+ Ca2+ Ca2+ Na+ Na+ Ca2+ Na+ Na+ Ca2+ Na+ Ca2+ Na+ Ca2+ Depolarization 10
- 11. 11 projection to brain olfactory receptor neuron cilia olfactory bulb inhaled air Olfactory Receptor Neurons 2007 Wolfers Kluwer Health | Lippincott Williams & Wilkins
- 12. 12 Active versus passive propagation? http://www.rci.rutgers.edu/~uzwiak/AnatPhys/ ChemicalSomaticSenses.htm axons olfactory receptor neurons cilia axon hillock brain olfactory system visual system photo- receptor neurons axons to brain cilia retina http://people.eecs.ku.edu/~miller/Courses/OpenGL/SampleProgramSet1/ images/HumanRetinaWithRodsAndCones.png
- 13. 13 Modality - cells have specialized receptors to sense external stimuli Cell Physiology Source Book 4th Edition, Figure 36.1
- 14. 14 Golfα Golfα AC3 GDP GTP ATP cAMP Ca2+ Cl– R OH Odorant TransducƟon current R*(A) β γ Review Tre GolfαGolfαAC3 GDPGTP ATP cAMP Ca2+ Cl– R OH Odorant TransducƟon current R* AcƟvatedreceptor (R*) [Odor (A)(B) β γ ReviewTrendsinNeurosciencesAugust GolfαGolfαAC3 GDPGTP ATP cAMP Ca2+ Cl– R OH Odorant TransducƟon current R* AcƟvatedreceptor (R*) [O (A)(B) β γ ReviewTrendsinNeurosciencesAug transduction current represent odor intensity, and which represent other infor- mation, such as odor quality? We consider several models of odor intensity coding at this level. Are they compatible with physiological data? Do they predict stable perception of odor quality over a range of concentrations? Although the neural code in the olfactory bulb must must be able to maintain a concentration-invariant repre- sentation of odor quality over biologically relevant concen- tration ranges to track the source. Although odors are generally thought to retain their quality over a range of concentrations, concentration changes greater than two orders of magnitude may yield changes in odor quality for some odorants [3,31] but not others [32]. Golfα Golfα AC3 GDP GTP ATP 1.0 0.5 0.0 1.0 0.5 0.0 1E-3 0.01 0.1 1 1E-3 0.01 0.1 1 cAMP Ca2+ Cl– R OH Odorant TransducƟon current R* TransducƟon current Spike firing Firingrate TransducƟon currentAcƟvatedreceptor (R*) Log [odorant] Log [odorant] [Odorant] (A) (B) (C) (D) Low High [Odorant] β γ TRENDS in Neurosciences Figure 1. Odorant concentration coding in olfactory sensory neurons (OSNs). During sensory transduction (A), odorant molecules bind and stabilize the active states of olfactory receptors (R) in ciliary membranes of OSNs. The activated receptors (R*) couple to G proteins (Golf) and increase synthesis of cyclic AMP (cAMP) by type III adenylyl cyclase (AC3). The cAMP opens cyclic nucleotide-gated channels that conduct calcium ions into the cilia and, in turn, open a channel (ANO2) mediating a depolarizing efflux of chloride ions. The resulting transduction current is passed to the OSN cell body, where it drives a train of action potentials (spikes). The concentration of detected odorant is encoded nonlinearly at each step of transduction: by a hyperbolic dependence of the number of activated receptors (R*) in the cilia (B), a strongly cooperative variation in amplitude of the transduction current (C), and similar sigmoidal variation of spike firing rate relayed by OSN axons (D). Data from [113] (C,D): response of normalized currents and firing rates of frog OSN to cineole; mammalian OSNs exhibit similar dose–response profiles. Review Trends in Neurosciences August 2014, Vol. 37, No. 8 syn transm axon hillock cell body dendrite cilia cilia axon synapse (glutamate) represent odor intensity, and which represent other infor- mation, such as odor quality? We consider several models of odor intensity coding at this level. Are they compatible with physiological data? Do they predict stable perception of odor quality over a range of concentrations? Although the neural code in the olfactory bulb must represent both odor concentration and identity it is crucial for the brain to disambiguate the two kinds of information. For olfactory navigation tasks, stimulus concentration varies with distance from a target odor source; animals must be able to maintain a concentration-invarian sentation of odor quality over biologically relevant tration ranges to track the source. Although od generally thought to retain their quality over a r concentrations, concentration changes greater th orders of magnitude may yield changes in odor for some odorants [3,31] but not others [32]. Spike rate coding Given that odorant concentration is correlated wit rates of OSN inputs to glomeruli, we may ask if t 0.5 0.0 1.0 0.5 0.0 1E-3 0.01 0.1 1 1E-3 0.01 0.1 1 TransducƟon current Spike firing Firingrate Transd curr Log [odorant] Log [odorant] (D) Low High [Odorant] TRENDS in Neuroscien Figure 1. Odorant concentration coding in olfactory sensory neurons (OSNs). During sensory transduction (A), odorant molecules bind and stabilize the activ olfactory receptors (R) in ciliary membranes of OSNs. The activated receptors (R*) couple to G proteins (Golf) and increase synthesis of cyclic AMP (cAMP) adenylyl cyclase (AC3). The cAMP opens cyclic nucleotide-gated channels that conduct calcium ions into the cilia and, in turn, open a channel (ANO2) m depolarizing efflux of chloride ions. The resulting transduction current is passed to the OSN cell body, where it drives a train of action potentials (spikes). The con of detected odorant is encoded nonlinearly at each step of transduction: by a hyperbolic dependence of the number of activated receptors (R*) in the cilia (B) cooperative variation in amplitude of the transduction current (C), and similar sigmoidal variation of spike firing rate relayed by OSN axons (D). Data from response of normalized currents and firing rates of frog OSN to cineole; mammalian OSNs exhibit similar dose–response profiles. 446 represent odor intensity, and which represent other infor- mation, such as odor quality? must be able to maintain a concentrati sentation of odor quality over biological Golfα Golfα AC3 GDP GTP ATP 1.0 0.5 0.0 1.0 0.5 0.0 1E-3 0.01 1E-3 0.01 cAMP Ca2+ Cl– R TransducƟon current R* TransducƟon current Spike firing Firingrate TransducƟon currentAcƟvatedreceptor (R*) Log [o Log [o [Od (A) (B) (C) (D) Low High [Odorant] β γ TREN Figure 1. Odorant concentration coding in olfactory sensory neurons (OSNs). During sensory transduction (A), odorant molecules bind and s olfactory receptors (R) in ciliary membranes of OSNs. The activated receptors (R*) couple to G proteins (Golf) and increase synthesis of cyc adenylyl cyclase (AC3). The cAMP opens cyclic nucleotide-gated channels that conduct calcium ions into the cilia and, in turn, open a ch depolarizing efflux of chloride ions. The resulting transduction current is passed to the OSN cell body, where it drives a train of action potentials of detected odorant is encoded nonlinearly at each step of transduction: by a hyperbolic dependence of the number of activated receptors (R* cooperative variation in amplitude of the transduction current (C), and similar sigmoidal variation of spike firing rate relayed by OSN axons response of normalized currents and firing rates of frog OSN to cineole; mammalian OSNs exhibit similar dose–response profiles. low high [Odorant] Information flow in olfactory receptor neurons 1. Sensory transduction to generate a graded receptor potential via cyclic nucleotide signalling. 2. Action potential generated at axon hillock if receptor potential is large enough. 3. Signal is transmitted to higher level neurons via synaptic release. 1. 2. 3. Mainland et al., 2014
- 15. 15 Transduction in the cilia of olfactory receptor neurons http://sites.sinauer.com/neuroscience5e/animations15.01.html
- 16. 16 Cilia organize channels, receptors and signalling machinery cilium dendrite to cell body odorantsreceptorion channel + depolarization spreads throughout dendrite + + + + + + + + + + +
- 17. 17 Cilia are microtubule-based organelles dendrite to cell body basal body (microtubules) axoneme (microtubules) cilium
- 18. 18 dendrite to cell body cilium The transition zone regulates what enters and leaves the cilium transition zone
- 19. 19 Molecular motors transport proteins along the cilium dendrite to cell body cilium kinesin dynein
- 20. 20 Name the numbered components 4 3 1 7 65 2
- 21. 21 What function do these components serve? 1. transition zone 2. kinesin 3. cilium
- 22. 22 Cilia have a broad biomedical relevance
- 23. Hua Jin central nervous system Rosenbaum & Witman, 2002 epithelial cells from kidney collecting tubule Alamy sperm Science Photo Library respiratory epithelium olfactory receptor neurons brain Motile cilia Primary sensory cilia Alamy sperm Science Photo Library respiratory epithelium Alamy sperm Science Photo Library respiratory epithelium Motile cilia Alamy sperm Science Photo Library respiratory epithelium 23
- 24. Cilia disorders affect most systems in the body blindness deafness chronic respiratory infection situs inversus heart disease infertility obesity cognitive dysfunction polydactyly kidney disease 24
- 25. 25 How do we study sensory systems?
- 26. Zeynep F. Altun www.wormatlas.org André Karwath/Wikimedia Commons oregonstate.edu/terra/2013/07/from-zebrafish-to-you/ http://www.healthyhomescoalition.org/mice-and-rats 26
- 27. 1) Known and reproducible neural anatomy 2) Short-lifespan 3) Freeze at -80 C 4) Small, sequenced genome 5) Easy to manipulate genetics and make mutants 6) Transparent (ease of imaging) 7) Inexpensive to work with wormatlas.org Caenorhabditis elegans 27
- 28. 28 C. elegans 60 ciliated sensory neurons sense chemical, thermal and mechanical stimuli head tail sensory neuron cell bodies sensory neuron cell bodies Michel Leroux & Tiffany Timbers axoneme axoneme basal body basal body
- 29. General approach to study the mechanism of sensation in C. elegans 1. Screen for abnormal sensory neuron development and function in mutants 2. Determine cellular and sub-cellular localization to infer function 3. Assess specific ciliated sensory neuron defects using synaptic and cilia markers in mutants 29
- 30. 30 What genes are important for sensation?
- 31. 31 Kwangjin Park & Tiffany Timbers Socket cell Cuticle Sheath cell Cilium Dendrite WT cilia mutantDiI DiI head tail Assay sensory neuron development and function in mutants: Dye-filling ciliated sensory neurons
- 32. 32 20x b wild-type efective mphid ciliated neurons hasmid ciliated neurons 480 deep-sequenced C. elegans strains from the multi-mutation Million Mutation Project (MMP) collection mixed-stage culture each strain tested separately (in duplicate) x 480 staining with fluorescent diI microscopy analysis: score amphids and phasmids separately for dye-filling plot results mutant C. elegans soak in a lipophilic dye examine under a microscope Timbers et al., under revision at Genome Research, 2015 tail neurons wild-type mutant Dye-filling procedure Assay sensory neuron development and function in mutants: Dye-filling head neurons wild-type mutant
- 33. 33 Timbers et al., under revision at Genome Research, 2015 0.00 0.25 0.50 0.75 1.00 0.00 0.25 0.50 0.75 1.00 Proportion of amphid defects Proportionofphasmiddefects c VC20615 VC20628 score amphids and phasmids separately for dye-filling plot results amphid and phasmid dye-fill defect amphid only dye-fill defect phasmid only dye-fill defect wild-type dye-filling wild-type head and tail neurons fail to fill with dye head neurons fail to fill with dye tail neurons fail to fill with dye Proportion of tail neuron defects Proportionofheadneurondefects Assay sensory neuron development and function in mutants: Dye-filling bgnt-1
- 34. C. elegans bgnt-1 is homologous to Mammalian B3gnt1 • hydrocephalus • Dandy-Walker malformation • seizures • encephalocele • retinal dysplasia • severe hypotonia (“floppy”) • increased creatine kinase (CK) levels • micropenis • multicystic kidneys • Mutations in human B3gnt1 lead to Walker Warburg syndrome, a disorder affecting the muscle, brain and eyes. • Walker Warburg syndrome symptoms in patients with B3gnt1 mutations: 34 Cilia disorder-related symptoms
- 35. C. elegans detect CO2 via ciliated BAG sensory neurons Assay sensory neuron development and function in mutants: CO2 avoidance wormatlas.org 35
- 36. C. elegans avoid CO2 36 Hallem et al., 2008
- 37. The Multi-worm Tracker Timbers et al., in preparation for PLoS Genetics, 2015 CO2 stimulus delivery image extraction post-experiment analysis 37
- 38. Timbers et al., in preparation for PLoS Genetics, 2015 Assay sensory neuron development and function in mutants: CO2 avoidance 38
- 39. Timbers et al., in preparation for PLoS Genetics, 2015 CO2 Assay sensory neuron development and function in mutants: CO2 avoidance 39
- 40. Hypothesis: gcy-9 and bbs-8 are required for detecting CO2 Timbers et al., in preparation for PLoS Genetics, 2015 CO2 40
- 41. 41 What role do these genes play in sensation?
- 42. 42 Fluorescent proteins and in vivo imaging can infer function cilia dendrite cell body axon synapses C. elegans ciliated sensory neuron GFPprotein of interest
- 43. 43 Protein likely has functions in transduction cilia dendrite cell body axon synapses C. elegans ciliated sensory neuron GFPprotein of interest
- 44. 44 Protein likely functions in synaptic transmission cilia dendrite cell body axon synapses C. elegans ciliated sensory neuron GFPprotein of interest
- 45. 45 head cilia BBS-7 BBS-7 localizes to cilia Mohan et al., 2013 motors cilia axoneme basal body
- 46. This protein localizes to cilia and synaptic endings of sensory neurons Chunmei Li cilia synapses CEP neurons cell bodies GFP-tagged protein 46
- 47. 47 What role does the protein play in the cilia and/or synapse?
- 48. 48 DAF-25::GFP is cilia localized Jensen et al., 2013
- 49. 49 Olfactory transduction in C. elegans Guanylate cyclase wild-type basal body Guanylate cyclase daf-25 mutant Dynein motor protein Jensen et al., 2013 Cilia basal body wormbook.org G-protein GFP
- 50. What C. elegans can tell us about sensation • What molecules participate in this process (e.g. dye-filling assay, sensory behaviour assays) • How these molecules contribute to sensation via their expression patterns (e.g. cilia versus synapse) • 30-40% genes in C. elegans have homologues (related genes) in humans, therefore many genes identified as important for sensation in C. elegans likely play similar roles in humans. 50
- 51. 51 Summary: How do animals sense the environment
- 52. projection to brain olfactory receptor neuron cilia olfactory bulb inhaled air 2007 Wolfers Kluwer Health | Lippincott Williams & Wilkins Olfactory neurons sense the odourants via sensory transduction in the cilia. This is propagated via action potentials and synaptic release to higher centres in the brain. 52
- 53. Cilia contributes to sensation by organizing molecules necessary for signal transduction in close approximation. 53 dendrite cilium kinesin dynein
- 54. Cilia disorders affect many systems in the body patients. This is due to almost every cell in our bodies having cilia to sense their environment. 54 blindness deafness chronic respiratory infection situs inversus heart disease infertility obesity cognitive dysfunction polydactyly kidney disease
- 55. C. elegans is a fantastic experimental model to study how animals sense the environment. 55 Slavica Berber Niels Ringstad/MITNiharb
Editor's Notes
- Zeynep F. Altun www.wormatlas.org
- The genetics screens utilize the free-living soil dwelling nematode, Caenorhabditis elegans, or more affectionately, C. elegans. List advantages. Mention that one advantage of performing a genetic screen for cilia-related phenotypes in C. elegans is that cilia are not required for organism reproduction and viability.
- maybe replace with a single bar graph…