Nervous and Sensory Systems!. Justin Rice bioTAjustin@yahoo.com Office Hours: 2-3, Thursdays,...

Nervous and Sensory Systems!

Justin RicebioTAjustin@yahoo.comOffice Hours: 2-3, Thursdays, Socrates Center

Recitations: Tuesdays 9:10-10:00 N C114, 7:00-7:50 W 116

VocabPineal gland pinea=pine conePons pons=bridgeLingual gyrus lingua=tongueHippocampus sea horseAmygdala almondGeniculate genu =knee e.g. genuflectionFusiform spindle shapedPulvinar pillowPyriform pear shapedVermis worm e.g. vermiform appendixIpsi same (e.g. ipsilateral cortex)Contra opposite, against (e.g. contralateral)

Reading list…Oliver Sacks…

-”Man who mistook his wife for a hat”-”The island of the colorblind”-”Musicophilia”

Eric Kandel-”In Search of Memory”

Division

Division

Sympathetic vs Parasympathetic Division

Sensory information enters brain via ‘’reticular formation’’

Info gets processed in different parts of your brain

Gustatory (Insula)

Smell (olfactory)

Can Mess with them using TMS (trans-cranial-magnetic-stimulation)

Motor and somatosensory cortex

Olfactory cortex (bulb)

Olfactory cortex (bulb)

Visual Cortex

Insula (gustatory cortex – a mysterious place)-also closely linked to addiction

Some MRIs

Some MRIs

Some MRIs

We’re focusing right

here

Taste

Each cell has different mechanism

Each cell has different

mechanism

Note: IP3=inositol triphosphate is another second messenger

Glutamate

Note: ~40 different bitter receptors in humans

Question 107

Certain medications selectively block certain ion channels. Which ion channel blocker would you expect to interfere with your sense of sweet taste?

a) Dihydropyridine – a voltage gated calcium channel blocker used to lower blood pressure

b) Delta-conotoxin – a poison from the cone snail that inhibits deactivation of voltage gated sodium channels

c) Pandinotoxin – a poison from the emperor scorpion, which inhibits the opening of voltage gated potassium channels

d) None of the abovee) All of the above

Question 107

Certain medications selectively block certain ion channels. Which ion channel blocker would you expect to interfere with your sense of sweet taste?

a) Dihydropyridine – a voltage gated calcium channel blocker used to lower blood pressure

b) Delta-conotoxin – a poison from the cone snail that inhibits deactivation of voltage gated sodium channels

c) Pandinotoxin – a poison from the emperor scorpion, which inhibits the opening of voltage gated potassium channels

d) None of the abovee) All of the above

Miracle Berries contain ‘’miraculin’’

-Strongly Binds to sweet receptor binding site at neutral pH-but only activates receptor at low pH

Question 108

What effect will miracle berries have on your taste of different foods?

a) Bitter foods will taste sweetb) Sweet foods will taste sourc) Sour foods will taste sweetd) Sweet foods will taste bittere) None of the above

Question 108

What effect will miracle berries have on your taste of different foods?

a) Bitter foods will taste sweetb) Sweet foods will taste sourc) Sour foods will taste sweetd) Sweet foods will taste bittere) None of the above

-Strongly Binds to sweet receptor binding site at neutral pH-but only activates receptor at low pH

Bitter tastes (~550 known)

cyanidestrychnine

Sweet tastes

Saccharin

steviol

Smell

-~900 receptors in humans-lots of gene duplication events

-Many odors activate multiple receptors-can smell gazillions of stuff

(refer to Dani’s lecture for details)

Smell

-~900 receptors in humans-lots of gene duplication events

-Many odors activate multiple receptors-can smell gazillions of stuff

(refer to Dani’s lecture for details)

Very weird

Smell

-Brain eating amoeba travels through cribriform plate!-first symptoms – altered sense of smell…

Stretch receptors in muscles (propioception)

Oligod

Mechanoreception-lots of different neurons, a few different receptor hypotheses:

Thermosensation

Speaker and Microphone

Solenoid – changing currentÞ changing magnetic field Þ magnet movesÞ Diaphragm movesÞ Air moves

Speaker and Microphone

Solenoid – changing currentÞ changing magnetic field Þ magnet movesÞ Diaphragm movesÞ Air moves

Speaker and Microphone

Solenoid – changing currentÞ changing magnetic field Þ magnet movesÞ Diaphragm movesÞ Air moves

Solenoid – Air moves =>Diaphragm movesÞ Magnet movesÞ Magnetic field changesÞ Current is induced

Hearing

Hearing

Hearing

Stapes pushes against perilymph-transmitting the sound waves

Hearing

Hearing

What about the frequency?

Basilar membrane gets wider towards the center – more floppy (lower resonance frequency)

Implicit Fourier decomposition

Amplification of soft sounds

Outer hair cells inner hair cells

(also contain a special motor protein, “prestin”, which can make them wiggle, amplifying the sound) => otoacoustic emissions

Question 109 Pesticide tributyltin has a very long half-life, and has been used for decades as a pesticide on ocean ship-bottoms, to avoid barnacle and algae growth. Recent studies have shown that tributyltin interferes with prestin function. One might expect this to cause:

a) Global warmingb) High affinity between dogs and tennis ballsc) partial-deafness in marine mammalsd) Corruption in congresse) None of the above

Cochlear implants

Gravity, movement sensation

Don’t forget plants!

Gravity, movement sensation

Don’t forget plants!

In the sacule(verticle)

In the utricle(horizontal)

Rotational Acceleration…

Question 110Sometimes, due to excessive shaking or head trama, otoliths can be rattled out of the utricle or saccule and into the semi-circular canals. What symptom would you imagine this would cause?

a) The ability to hear gravityb) Sensation of falling when you turn your headc) Sensation of spinning when you stand upd) Sensation of falling when you hear a noisee) None of the above

Question 110Sometimes, due to excessive shaking or head trama, otoliths can be rattled out of the utricle or saccule and into the semi-circular canals. What symptom would you imagine this would cause?

a) The ability to hear gravityb) Sensation of falling when you turn your headc) Sensation of spinning when you stand upd) Sensation of falling when you hear a noisee) None of the above

Question 110Sometimes, due to excessive shaking or head trama, otoliths can be rattled out of the utricle or saccule and into the semi-circular canals. What symptom would you imagine this would cause?

a) The ability to hear gravityb) Sensation of falling when you turn your headc) Sensation of spinning when you stand upd) Sensation of falling when you hear a noisee) None of the above

(Benign paroxysmal positional vertigo) - ~1 million doctor visits/year

Question 110Sometimes, due to excessive shaking or head trama, otoliths can be rattled out of the utricle or saccule and into the semi-circular canals. What symptom would you imagine this would cause?

a) The ability to hear gravityb) Sensation of falling when you turn your headc) Sensation of spinning when you stand upd) Sensation of falling when you hear a noisee) None of the above

(Benign paroxysmal positional vertigo) - ~1 million doctor visits/year

Vision

Vision

Cones and Rods, bipolar and ganglion cells

Vision

Vision

fovea

Macula=spot

Optic nerve

Retinal artery

Vision

Very different appearance

Rods are very sensitive-black and white vision

Cones come in red, blue, and green flavors, and sense color

Both Release GLUTAMATE when depolarized

Rods

Vision Both have membrane stacks

Vision Light causes cis-trans isomerizationRhodopsin changes shape

Rods: Black and White (really, purple) Vision

What does phosphodiesterase do?

Cyclic GMP GMP

It cleaves a phospho-diester bond

Question 111Lets say you were staring out the window during the day, when all of a sudden a phosphodiesterase inhibitor was introduced to the rod cells in your eyes?

a) The membrane voltage will go up, and the rods will release more glutamate

b) The membrane voltage will go down, and the rods will release less glutamate

c) The membrane voltage will go down, and the rods will release less acetylcholine

d) The membrane voltage will go up, and the rods will release more acetylcholine

e) None of the above

Question 111Lets say you were staring out the window during the day, when all of a sudden a phosphodiesterase inhibitor was introduced to the rod cells in your eyes?

a) The membrane voltage will go up, and the rods will release more glutamate

b) The membrane voltage will go down, and the rods will release less glutamate

c) The membrane voltage will go down, and the rods will release less acetylcholine

d) The membrane voltage will go up, and the rods will release more acetylcholine

e) None of the above

PDE causes cGMP->GMP-> sodium channels close

-> membrane voltage becomes more negative-> less glutamate is released.

PDE inhibitor - > opposite series of events -> more glutamate is released

Question 111Lets say you were staring out the window during the day, when all of a sudden a phosphodiesterase inhibitor was introduced to the rod cells in your eyes?

a) The membrane voltage will go up, and the rods will release more glutamate

b) The membrane voltage will go down, and the rods will release less glutamate

c) The membrane voltage will go down, and the rods will release less acetylcholine

d) The membrane voltage will go up, and the rods will release more acetylcholine

e) None of the above

Color VisionDifferent cones express different “iodopsins”

Same mechanism as rhodopsin, but differ by a few amino acids to change absorption peaks

Coordination in retina

In darkness, rods and cones (at ~-40mV) are constantly releasing glutamate

-with light, Na+ channels close, cells hyperpolarize, and glutamate stops. -in response, some bipolar cells depolarize, while others hyperpolarize

Question 112Given their two opposite responses to glutamate, we might guess that bipolar cells…

a) Each have both glutamate-binding sodium channels and glutamate binding chlorine channels

b) Come in two types, one with glutamate-gated sodium channels, and one with acetylcholine-gated sodium channels

c) Come in two types, one with glutamate-gated sodium channels, and one with a metabotropic glutamate receptor, which causes the closing of calcium/sodium channels

d) None of the abovee) All of the above

Question 112Given their two opposite responses to glutamate, we might guess that bipolar cells…

a) Each have both glutamate-binding sodium channels and glutamate binding chlorine channels

b) Come in two types, one with glutamate-gated sodium channels, and one with acetylcholine-gated sodium channels

c) Come in two types, one with glutamate-gated sodium channels, and one with a metabotropic glutamate receptor, which causes the closing of calcium/sodium channels

d) None of the abovee) All of the above

Question 112Given their two opposite responses to glutamate, we might guess that bipolar cells…

a) Each have both glutamate-binding sodium channels and glutamate binding chlorine channels

b) Come in two types, one with glutamate-gated sodium channels, and one with acetylcholine-gated sodium channels

c) Come in two types, one with glutamate-gated sodium channels, and one with a metabotropic glutamate receptor, which causes the closing of calcium/sodium channels

d) None of the abovee) All of the above

OFF vs ON bipolar cells

Question 113The phosphodiesterase in rod and cone cells is PDE6. Sildafenil (Viagra) is a well known PDE5 inhibitor, but it has also been shown to partially inhibitor PDE6. A common side effect of Viagra is cyanopsia (blue vision), indicating that sildenafil somehow works differently on some cone cells than others. Given what you know from class, pick the most likely cause:

a) Sildenafil is a better inhibitor of PDE6 in S than it is in M and L cone cells

b) Sildenafil is a better inhibitor of PDE6 in L than it is in S and M cone cells

c) Sildenafil is a worse inhibitor of PDE6 in L than it is in S and M cone cells

d) Sildenafil is a worse inhibitor of PDE6 in S than it is in M and L cone cells

Question 113The phosphodiesterase in rod and cone cells is PDE6. Sildafenil (Viagra) is a well known PDE5 inhibitor, but it has also been shown to partially inhibitor PDE6. A common side effect of Viagra is cyanopsia (blue vision), indicating that sildenafil somehow works differently on some cone cells than others. Given what you know from class, pick the most likely cause:

a) Sildenafil is a better inhibitor of PDE6 in S than it is in M and L cone cells

b) Sildenafil is a better inhibitor of PDE6 in L than it is in S and M cone cells

c) Sildenafil is a worse inhibitor of PDE6 in L than it is in S and M cone cells

d) Sildenafil is a worse inhibitor of PDE6 in S than it is in M and L cone cells

Question 113The phosphodiesterase in rod and cone cells is PDE6. Sildafenil (Viagra) is a well known PDE5 inhibitor, but it has also been shown to partially inhibitor PDE6. A common side effect of Viagra is cyanopsia (blue vision), indicating that sildenafil somehow works differently on some cone cells than others. Given what you know from class, pick the most likely cause:

a) Sildenafil is a better inhibitor of PDE6 in S than it is in M and L cone cells

b) Sildenafil is a better inhibitor of PDE6 in L than it is in S and M cone cells

c) Sildenafil is a worse inhibitor of PDE6 in L than it is in S and M cone cells

d) Sildenafil is a worse inhibitor of PDE6 in S than it is in M and L cone cells

normally phosphodiesterase deactivates cGMP-GMP->closes Na+ channels ->hyperpolarizes cone cells ->stops glutamate from going to Bipolar cells

->causes sensation of “seeing something”

Question 113The phosphodiesterase in rod and cone cells is PDE6. Sildafenil (Viagra) is a well known PDE5 inhibitor, but it has also been shown to partially inhibitor PDE6. A common side effect of Viagra is cyanopsia (blue vision), indicating that sildenafil somehow works differently on some cone cells than others. Given what you know from class, pick the most likely cause:

a) Sildenafil is a better inhibitor of PDE6 in S than it is in M and L cone cells

b) Sildenafil is a better inhibitor of PDE6 in L than it is in S and M cone cells

c) Sildenafil is a worse inhibitor of PDE6 in L than it is in S and M cone cells

d) Sildenafil is a worse inhibitor of PDE6 in S than it is in M and L cone cells

normally phosphodiesterase deactivates cGMP-GMP->closes Na+ channels ->hyperpolarizes cone cells ->stops glutamate from going to Bipolar cells

->causes sensation of “seeing something”Inhibiting PDE6 in an S cell causes you to not see blue

-> must work better in M and L cells

Question 113The phosphodiesterase in rod and cone cells is PDE6. Sildafenil (Viagra) is a well known PDE5 inhibitor, but it has also been shown to partially inhibitor PDE6. A common side effect of Viagra is cyanopsia (blue vision), indicating that sildenafil somehow works differently on some cone cells than others. Given what you know from class, pick the most likely cause:

a) Sildenafil is a better inhibitor of PDE6 in S than it is in M and L cone cells

b) Sildenafil is a better inhibitor of PDE6 in L than it is in S and M cone cells

c) Sildenafil is a worse inhibitor of PDE6 in L than it is in S and M cone cells

d) Sildenafil is a worse inhibitor of PDE6 in S than it is in M and L cone cells

Question 114Blood is supplied to the rods, cones, bipolar cells, and ganglion via the retinal artery, which branches out into little arterioles, shown on the right. High intraocular pressure can collapse these arterioles, leading to the slow hypoxic death of ganglion cells (this is called ‘’glaucoma’’)This process begins farthest from the optic nerve, and slowly progresses inward. What would you expect to be symptoms of glaucoma?

a) Progressive loss of color vision around the focal pointb) Progressive loss of peripheral vision (both color and black/white)c) Progressive loss of color peripheral visiond) Progressive loss of black and white vision around the focal pointe) Progressive loss of all vision at the focal point

Question 114Blood is supplied to the rods, cones, bipolar cells, and ganglion via the retinal artery, which branches out into little arterioles, shown on the right. High intraocular pressure can collapse these arterioles, leading to the slow hypoxic death of ganglion cells (this is called ‘’glaucoma’’)This process begins farthest from the optic nerve, and slowly progresses inward. What would you expect to be symptoms of glaucoma?

a) Progressive loss of color vision around the focal pointb) Progressive loss of peripheral vision (both color and black/white)c) Progressive loss of color peripheral visiond) Progressive loss of black and white vision around the focal pointe) Progressive loss of all vision at the focal point

Question:

Question:

Various colorblindnesses

Question 115The gene for S-cone opsin (blue) is on chromosome 7, while the genes for L-cone (red) and M-cone (green) opsin are on the X chromosome. Colorblindness caused by problems with opsin is a recessive trait.Let’s say a man who can’t see green has children with a woman with normal vision. Their first is a son, who can’t see red. What’s the likelyhood that their second son can see red?

a) 0%b) 25%c) 50%d) 75%e) 100%

Question 115The gene for S-cone opsin (blue) is on chromosome 7, while the genes for L-cone (red) and M-cone (green) opsin are on the X chromosome. Colorblindness caused by problems with opsin is a recessive trait.Let’s say a man who can’t see green has children with a woman with normal vision. Their first is a son, who can’t see red. What’s the likelyhood that their second son can see red?

a) 0%b) 25%c) 50%d) 75%e) 100%

Dad: XR YMom: XR XRXR XRY

Xr XrXR XrY

What if we had more iodopsins?

Birds have 4(can see in UV)“tetra-chromats”

What if we had more iodopsins?

Birds have 4(can see in UV)“tetra-chromats”

So do some women! (red and green opsin genes are on X chromosome) – can be mosaic for different iodopsins

What if we had more iodopsins?

Birds have 4(can see in UV)“tetra-chromats”

Mantis-shrimp have 20!

So do some women! (red and green opsin genes are on X chromosome) – can be mosaic for different iodopsins

Melanopsin! (just for fun)

Found in ‘’intrinsically photosensitive retinal ganglion cells” (ipRGCs)

Absorb blue/violet light, ~460nm

Modulate circadian rhythmand pupil dilation reflex

Cis retinal is “dichroic”

Cis retinal is “dichroic”

Cis retinal is “dichroic”

Squid and octopus can see polarization of light

Squid and octopus can see polarization of light

Squid and octopus can see polarization of light

Squid and octopus can see polarization of light

Channel Rhodopsinfound in algae

How about fluorescent sensing?Fuse two genes – Green Fluorescent protein and Calmodulin

-Genetically engineer to be expressed in some neurons, but not others

-when calcium is present, it binds to calmodulin, which changes shape, thus changing the shape of the GFP, thus changing the color of GFP

-can visualize synaptic activity

Sea turtles can sense electromagnetic fields

No one really understands how – best guess is that they use light to homolytically break a bond (probably in a cryptochrome) to form a radical pair-which then does some weird quantum mechanical thing

Sea turtles can sense electromagnetic fields

No one really understands how – best guess is that they use light to homolytically break a bond (probably in a cryptochrome) to form a radical pair-which then does some weird quantum mechanical thing

Explain this!