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

2

http://smallbusinessbonfire.com/do-your-services-pass-the-sniff-test

http://wabikes.org/2010/11/15/stop-signs-the-kudzu-of-american-bike-paths/3

https://s-media-cache-ak0.pinimg.com/736x/90/13/4c/ 90134cdcb39ab99d7485a34f199f615c.jpg

4

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

6http://www.wikicell.org/eightSystemImage/sensorySystem/Sensory%20System.jpg

touch temperature pain

Human Sensory Systems

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

Reminder: Action Potential Generation

extracellular

intracellular

Na+

Ca2+

Na+

Na+

Na+

Ca2+Ca2+Ca2+

Na+

Na+

Ca2+

Na+

Resting state

8

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

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

projection to brain

olfactory receptor neuron

cilia

olfactory bulb

inhaled air

Olfactory Receptor Neurons

2007 Wolfers Kluwer Health | Lippincott Williams & Wilkins

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

Modality - cells have specialized receptors to sense external stimuli

Cell Physiology Source Book 4th Edition, Figure 36.1

14

represent odor intensity, and which represent other infor-mation, such as odor quality?

We consider several models of odor intensity coding atthis level. Are they compatible with physiological data? Dothey predict stable perception of odor quality over a rangeof concentrations?

Although the neural code in the olfactory bulb mustrepresent both odor concentration and identity it is crucialfor the brain to disambiguate the two kinds of information.For olfactory navigation tasks, stimulus concentrationvaries with distance from a target odor source; animals

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 aregenerally thought to retain their quality over a range ofconcentrations, concentration changes greater than twoorders of magnitude may yield changes in odor qualityfor some odorants [3,31] but not others [32].

Spike rate codingGiven that odorant concentration is correlated with spikerates of OSN inputs to glomeruli, we may ask if this rate

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

cAMPCa2+

Cl–

R

OH

Odorant

Transduc!oncurrent

R*

Transduc!oncurrent

Spike firing

Firin

g ra

teTr

ansd

uc!o

ncu

rren

tAc

!vat

ed re

cept

or(R

*)

Log [odorant]

Log [odorant]

[Odorant]

(A) (B)

(C)

(D)

Low

High

[Odorant]

βγ

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 ofolfactory 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 IIIadenylyl cyclase (AC3). The cAMP opens cyclic nucleotide-gated channels that conduct calcium ions into the cilia and, in turn, open a channel (ANO2) mediating adepolarizing 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 concentrationof 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 stronglycooperative 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

446

represent odor intensity, and which represent other infor-mation, such as odor quality?

We consider several models of odor intensity coding atthis level. Are they compatible with physiological data? Dothey predict stable perception of odor quality over a rangeof concentrations?

Although the neural code in the olfactory bulb mustrepresent both odor concentration and identity it is crucialfor the brain to disambiguate the two kinds of information.For olfactory navigation tasks, stimulus concentrationvaries with distance from a target odor source; animals

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 aregenerally thought to retain their quality over a range ofconcentrations, concentration changes greater than twoorders of magnitude may yield changes in odor qualityfor some odorants [3,31] but not others [32].

Spike rate codingGiven that odorant concentration is correlated with spikerates of OSN inputs to glomeruli, we may ask if this rate

GolfαGolfαAC3

GDPGTP

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

cAMPCa2+

Cl–

R

OH

Odorant

Transduc!oncurrent

R*

Transduc!oncurrent

Spike firing

Firing rate

Transduc!on

current

Ac!vated receptor

(R*)

Log [odorant]

Log [odorant]

[Odorant]

(A) (B)

(C)

(D)

Low

High

[Odorant]

βγ

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 ofolfactory 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 IIIadenylyl cyclase (AC3). The cAMP opens cyclic nucleotide-gated channels that conduct calcium ions into the cilia and, in turn, open a channel (ANO2) mediating adepolarizing 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 concentrationof 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 stronglycooperative 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.

ReviewTrends in Neurosciences August 2014, Vol. 37, No. 8

446

represent odor intensity, and which represent other infor-mation, such as odor quality?

We consider several models of odor intensity coding atthis level. Are they compatible with physiological data? Dothey predict stable perception of odor quality over a rangeof concentrations?

Although the neural code in the olfactory bulb mustrepresent both odor concentration and identity it is crucialfor the brain to disambiguate the two kinds of information.For olfactory navigation tasks, stimulus concentrationvaries with distance from a target odor source; animals

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 aregenerally thought to retain their quality over a range ofconcentrations, concentration changes greater than twoorders of magnitude may yield changes in odor qualityfor some odorants [3,31] but not others [32].

Spike rate codingGiven that odorant concentration is correlated with spikerates of OSN inputs to glomeruli, we may ask if this rate

GolfαGolfαAC3

GDPGTP

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

cAMPCa2+

Cl–

R

OH

Odorant

Transduc!oncurrent

R*

Transduc!oncurrent

Spike firing

Firing rate

Transduc!on

current

Ac!vated receptor

(R*)

Log [odorant]

Log [odorant]

[Odorant]

(A) (B)

(C)

(D)

Low

High

[Odorant]

βγ

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 ofolfactory 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 IIIadenylyl cyclase (AC3). The cAMP opens cyclic nucleotide-gated channels that conduct calcium ions into the cilia and, in turn, open a channel (ANO2) mediating adepolarizing 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 concentrationof 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 stronglycooperative 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.

ReviewTrends in Neurosciences August 2014, Vol. 37, No. 8

446

transductioncurrent

represent odor intensity, and which represent other infor-mation, such as odor quality?

We consider several models of odor intensity coding atthis level. Are they compatible with physiological data? Dothey predict stable perception of odor quality over a rangeof concentrations?

Although the neural code in the olfactory bulb mustrepresent both odor concentration and identity it is crucialfor the brain to disambiguate the two kinds of information.For olfactory navigation tasks, stimulus concentrationvaries with distance from a target odor source; animals

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 aregenerally thought to retain their quality over a range ofconcentrations, concentration changes greater than twoorders of magnitude may yield changes in odor qualityfor some odorants [3,31] but not others [32].

Spike rate codingGiven that odorant concentration is correlated with spikerates of OSN inputs to glomeruli, we may ask if this rate

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

cAMPCa2+

Cl–

R

OH

Odorant

Transduc!oncurrent

R*

Transduc!oncurrent

Spike firing

Firing rate

Transduc!on

current

Ac!vated receptor

(R*)

Log [odorant]

Log [odorant]

[Odorant]

(A) (B)

(C)

(D)

Low

High

[Odorant]

βγ

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 ofolfactory 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 IIIadenylyl cyclase (AC3). The cAMP opens cyclic nucleotide-gated channels that conduct calcium ions into the cilia and, in turn, open a channel (ANO2) mediating adepolarizing 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 concentrationof 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 stronglycooperative 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

446

synaptic transmission

axon hillock

cellbody

dend

rite

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 atthis level. Are they compatible with physiological data? Dothey predict stable perception of odor quality over a rangeof concentrations?

Although the neural code in the olfactory bulb mustrepresent both odor concentration and identity it is crucialfor the brain to disambiguate the two kinds of information.For olfactory navigation tasks, stimulus concentrationvaries with distance from a target odor source; animals

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 aregenerally thought to retain their quality over a range ofconcentrations, concentration changes greater than twoorders of magnitude may yield changes in odor qualityfor some odorants [3,31] but not others [32].

Spike rate codingGiven that odorant concentration is correlated with spikerates of OSN inputs to glomeruli, we may ask if this rate

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

cAMPCa2+

Cl–

R

OH

Odorant

Transduc!oncurrent

R*

Transduc!oncurrent

Spike firing

Firin

g ra

teTr

ansd

uc!o

ncu

rren

tAc

!vat

ed re

cept

or(R

*)

Log [odorant]

Log [odorant]

[Odorant]

(A) (B)

(C)

(D)

Low

High

[Odorant]

βγ

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 ofolfactory 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 IIIadenylyl cyclase (AC3). The cAMP opens cyclic nucleotide-gated channels that conduct calcium ions into the cilia and, in turn, open a channel (ANO2) mediating adepolarizing 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 concentrationof 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 stronglycooperative 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

446

represent odor intensity, and which represent other infor-mation, such as odor quality?

We consider several models of odor intensity coding atthis level. Are they compatible with physiological data? Dothey predict stable perception of odor quality over a rangeof concentrations?

Although the neural code in the olfactory bulb mustrepresent both odor concentration and identity it is crucialfor the brain to disambiguate the two kinds of information.For olfactory navigation tasks, stimulus concentrationvaries with distance from a target odor source; animals

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 aregenerally thought to retain their quality over a range ofconcentrations, concentration changes greater than twoorders of magnitude may yield changes in odor qualityfor some odorants [3,31] but not others [32].

Spike rate codingGiven that odorant concentration is correlated with spikerates of OSN inputs to glomeruli, we may ask if this rate

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

cAMPCa2+

Cl–

R

OH

Odorant

Transduc!oncurrent

R*

Transduc!oncurrent

Spike firing

Firin

g ra

teTr

ansd

uc!o

ncu

rren

tAc

!vat

ed re

cept

or(R

*)

Log [odorant]

Log [odorant]

[Odorant]

(A) (B)

(C)

(D)

Low

High

[Odorant]

βγ

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 ofolfactory 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 IIIadenylyl cyclase (AC3). The cAMP opens cyclic nucleotide-gated channels that conduct calcium ions into the cilia and, in turn, open a channel (ANO2) mediating adepolarizing 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 concentrationof 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 stronglycooperative 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

446

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

Transduction in the cilia of olfactory receptor neurons

http://sites.sinauer.com/neuroscience5e/animations15.01.html

16

Cilia organize channels, receptors and signalling machinery

ciliumdendrite

to cell body

odorantsreceptorion channel

+

depolarization spreads throughout dendrite+++ +

+

++ +

+ +

+

17

Cilia are microtubule-based organelles

dendriteto cell body

basal body(microtubules)

axoneme (microtubules)

cilium

18

dendriteto cell body

cilium

The transition zone regulates what enters and leaves the cilium

transition zone

19

Molecular motors transport proteins along the cilium

dendriteto cell body

cilium

kinesin

dynein

20

Name the numbered components

4

3

1 7

65

2

21

What function do these components serve?

1. transition zone

2. kinesin

3. cilium

22

Cilia have a broad biomedical relevance

Hua Jin

central nervous system

Rosenbaum & Witman, 2002

epithelial cells from kidney collecting tubule

Alamy

sperm

Science Photo Library

respiratory epithelium

olfactory receptor neuronsbrain

Motile cilia

Primary sensory cilia

Alamy

sperm

Science Photo Library

respiratory epithelium

Alamy

sperm

Science Photo Library

respiratory epitheliumMotile cilia

Alamy

sperm

Science Photo Library

respiratory epithelium

23

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

How do we study sensory systems?

Zeynep F. Altunwww.wormatlas.org

André Karwath/Wikimedia Commons

oregonstate.edu/terra/2013/07/from-zebrafish-to-you/

http://www.healthyhomescoalition.org/mice-and-rats

26

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

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

basalbody

basalbody

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

What genes are important for sensation?

31

Kwangjin Park & Tiffany Timbers

Socket cell

Cuticle

Sheath cell

Cilium

Dendrite

WT cilia mutant DiI

DiI

head

tail

Assay sensory neuron development and function in mutants: Dye-filling

ciliated sensoryneurons

32

0.00

0.25

0.50

0.75

1.00

0.00 0.25 0.50 0.75 1.00Proportion of amphid defects

Pro

porti

on o

f pha

smid

def

ects

20x

a b

wild-type

defective

c

Timbers et al., Figure 1

VC20615

VC20628

amphid ciliated neurons

wild-typedye-filling

defectivedye-filling

wild-typedye-filling

defectivedye-filling

phasmid ciliated neurons

480 deep-sequencedC. elegans strains fromthe multi-mutationMillion Mutation Project(MMP) collection

mixed-stageculture

each strain testedseparately (in duplicate)

x 480

staining withfluorescent diI

microscopy analysis:score amphids andphasmids separatelyfor dye-filling

plot results

amphid andphasmiddye-fill defect

amphid onlydye-fill defect

phasmid onlydye-fill defect

wild-typedye-filling

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

33Timbers 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 1.00Proportion of amphid defects

Pro

porti

on o

f pha

smid

def

ects

20x

a b

wild-type

defective

c

Timbers et al., Figure 1

VC20615

VC20628

amphid ciliated neurons

wild-typedye-filling

defectivedye-filling

wild-typedye-filling

defectivedye-filling

phasmid ciliated neurons

480 deep-sequencedC. elegans strains fromthe multi-mutationMillion Mutation Project(MMP) collection

mixed-stageculture

each strain testedseparately (in duplicate)

x 480

staining withfluorescent diI

microscopy analysis:score amphids andphasmids separatelyfor dye-filling

plot results

amphid andphasmiddye-fill defect

amphid onlydye-fill defect

phasmid onlydye-fill defect

wild-typedye-fillingwild-type

head and tail neurons fail to fill with dye

head neurons fail to fill with dyetail neurons fail to fill with dye

Proportion of tail neuron defects

Prop

ortio

n of

hea

d ne

uron

def

ects

Assay sensory neuron development and function in mutants: Dye-filling

bgnt-1

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:

34Cilia disorder-related symptoms

C. elegans detect CO2 via ciliated BAG sensory neurons

Assay sensory neuron development and function in mutants: CO2 avoidance

wormatlas.org35

C. elegans avoid CO2

36

Hallem et al., 2008

The Multi-worm Tracker

Timbers et al., in preparation for PLoS Genetics, 2015

CO2 stimulus delivery

image extraction

post-experimentanalysis

37

Timbers et al., in preparation for PLoS Genetics, 2015

Assay sensory neuron development and function in mutants: CO2 avoidance

38

Timbers et al., in preparation for PLoS Genetics, 2015

CO2

Assay sensory neuron development and function in mutants: CO2 avoidance

39

Hypothesis: gcy-9 and bbs-8 are required for detecting CO2

Timbers et al., in preparation for PLoS Genetics, 2015

CO2

40

41

What role do these genes play in sensation?

42

Fluorescent proteins and in vivo imaging can infer function

ciliadendrite

cell body

axonsynapses

C. elegans ciliated sensory neuron

GFPprotein of interest

43

Protein likely has functions in transduction

ciliadendrite

cell body

axonsynapses

C. elegans ciliated sensory neuron

GFPprotein of interest

44

Protein likely functions in synaptic transmission

ciliadendrite

cell body

axonsynapses

C. elegans ciliated sensory neuron

GFPprotein of interest

45

head cilia

BBS-7

BBS-7 localizes to cilia

Mohan et al., 2013

motors

cilia axoneme

basalbody

This protein localizes to cilia and synaptic endings of sensory neurons

Chunmei Li

cilia synapses

CEP neurons

cell bodiesGFP-tagged protein

46

47

What role does the protein play in the cilia and/or synapse?

48

DAF-25::GFP is cilia localized

Jensen et al., 2013

49

Olfactory transduction in C. elegans

Guanylate cyclasewild-type

basal body

Guanylate cyclasedaf-25 mutant

Dynein motor protein

Jensen et al., 2013

Ciliabasal body

wormbook.org

G-protein

GFP

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

Summary:

How do animals sense the environment

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

Cilia contributes to sensation by organizing molecules necessary for signal transduction in close approximation.

53dendrite

to cell body

cilium

kinesin

dynein

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

C. elegans is a fantastic experimental model to study how animals sense the environment.

55

Slavica Berber

Niels Ringstad/MITNiharb