Nervous and Sensory Systems!

Justin Rice bioTAjustin@yahoo Justin Rice bioTAjustin@yahoo.com Office Hours: 2-3, Thursdays, Socrates Center Recitations: Tuesdays 9:10-10:00 N C114, 7:00-7:50 W 116

Vocab Pineal gland pinea=pine cone Pons pons=bridge Lingual gyrus lingua=tongue Hippocampus sea horse Amygdala almond Geniculate genu =knee e.g. genuflection Fusiform spindle shaped Pulvinar pillow Pyriform pear shaped Vermis worm e.g. vermiform appendix Ipsi 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 Glutamate Note: IP3=inositol triphosphate is another second messenger 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? Dihydropyridine – a voltage gated calcium channel blocker used to lower blood pressure Delta-conotoxin – a poison from the cone snail that inhibits deactivation of voltage gated sodium channels Pandinotoxin – a poison from the emperor scorpion, which inhibits the opening of voltage gated potassium channels None of the above 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? Dihydropyridine – a voltage gated calcium channel blocker used to lower blood pressure Delta-conotoxin – a poison from the cone snail that inhibits deactivation of voltage gated sodium channels Pandinotoxin – a poison from the emperor scorpion, which inhibits the opening of voltage gated potassium channels None of the above 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? Bitter foods will taste sweet Sweet foods will taste sour Sour foods will taste sweet Sweet foods will taste bitter None of the above

Question 108 What effect will miracle berries have on your taste of different foods? Bitter foods will taste sweet Sweet foods will taste sour Sour foods will taste sweet Sweet foods will taste bitter 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) strychnine cyanide

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 Very weird -~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 -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 current changing magnetic field magnet moves Diaphragm moves Air moves

Speaker and Microphone Solenoid – changing current changing magnetic field magnet moves Diaphragm moves Air moves

Speaker and Microphone Solenoid – changing current changing magnetic field magnet moves Diaphragm moves Air moves Solenoid – Air moves =>Diaphragm moves Magnet moves Magnetic field changes 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: Global warming High affinity between dogs and tennis balls partial-deafness in marine mammals Corruption in congress None of the above

Cochlear implants

Gravity, movement sensation Don’t forget plants!

Gravity, movement sensation Don’t forget plants! In the utricle (horizontal) In the sacule (verticle)

Rotational Acceleration…

Question 110 Sometimes, 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? The ability to hear gravity Sensation of falling when you turn your head Sensation of spinning when you stand up Sensation of falling when you hear a noise None of the above

Question 110 Sometimes, 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? The ability to hear gravity Sensation of falling when you turn your head Sensation of spinning when you stand up Sensation of falling when you hear a noise None of the above

Question 110 Sometimes, 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? The ability to hear gravity Sensation of falling when you turn your head Sensation of spinning when you stand up Sensation of falling when you hear a noise None of the above (Benign paroxysmal positional vertigo) - ~1 million doctor visits/year

Question 110 Sometimes, 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? The ability to hear gravity Sensation of falling when you turn your head Sensation of spinning when you stand up Sensation of falling when you hear a noise None of the above (Benign paroxysmal positional vertigo) - ~1 million doctor visits/year

Vision

Vision Cones and Rods, bipolar and ganglion cells

Vision

Vision Optic nerve Retinal artery fovea Macula=spot

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 isomerization Rhodopsin changes shape

Rods: Black and White (really, purple) Vision

What does phosphodiesterase do? Cyclic GMP GMP It cleaves a phospho-diester bond

Question 111 Lets 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? The membrane voltage will go up, and the rods will release more glutamate The membrane voltage will go down, and the rods will release less glutamate The membrane voltage will go down, and the rods will release less acetylcholine The membrane voltage will go up, and the rods will release more acetylcholine None of the above

Question 111 Lets 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? The membrane voltage will go up, and the rods will release more glutamate The membrane voltage will go down, and the rods will release less glutamate The membrane voltage will go down, and the rods will release less acetylcholine The membrane voltage will go up, and the rods will release more acetylcholine 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 111 Lets 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? The membrane voltage will go up, and the rods will release more glutamate The membrane voltage will go down, and the rods will release less glutamate The membrane voltage will go down, and the rods will release less acetylcholine The membrane voltage will go up, and the rods will release more acetylcholine None of the above

Color Vision Different 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 112 Given their two opposite responses to glutamate, we might guess that bipolar cells… Each have both glutamate-binding sodium channels and glutamate binding chlorine channels Come in two types, one with glutamate-gated sodium channels, and one with acetylcholine-gated sodium channels 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 None of the above All of the above

Question 112 Given their two opposite responses to glutamate, we might guess that bipolar cells… Each have both glutamate-binding sodium channels and glutamate binding chlorine channels Come in two types, one with glutamate-gated sodium channels, and one with acetylcholine-gated sodium channels 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 None of the above All of the above

Question 112 Given their two opposite responses to glutamate, we might guess that bipolar cells… Each have both glutamate-binding sodium channels and glutamate binding chlorine channels Come in two types, one with glutamate-gated sodium channels, and one with acetylcholine-gated sodium channels 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 None of the above All of the above

OFF vs ON bipolar cells

Question 113 The 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: Sildenafil is a better inhibitor of PDE6 in S than it is in M and L cone cells Sildenafil is a better inhibitor of PDE6 in L than it is in S and M cone cells Sildenafil is a worse inhibitor of PDE6 in L than it is in S and M cone cells Sildenafil is a worse inhibitor of PDE6 in S than it is in M and L cone cells

Question 113 The 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: Sildenafil is a better inhibitor of PDE6 in S than it is in M and L cone cells Sildenafil is a better inhibitor of PDE6 in L than it is in S and M cone cells Sildenafil is a worse inhibitor of PDE6 in L than it is in S and M cone cells Sildenafil is a worse inhibitor of PDE6 in S than it is in M and L cone cells

Question 113 The 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: Sildenafil is a better inhibitor of PDE6 in S than it is in M and L cone cells Sildenafil is a better inhibitor of PDE6 in L than it is in S and M cone cells Sildenafil is a worse inhibitor of PDE6 in L than it is in S and M cone cells 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 113 The 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: Sildenafil is a better inhibitor of PDE6 in S than it is in M and L cone cells Sildenafil is a better inhibitor of PDE6 in L than it is in S and M cone cells Sildenafil is a worse inhibitor of PDE6 in L than it is in S and M cone cells 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 113 The 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: Sildenafil is a better inhibitor of PDE6 in S than it is in M and L cone cells Sildenafil is a better inhibitor of PDE6 in L than it is in S and M cone cells Sildenafil is a worse inhibitor of PDE6 in L than it is in S and M cone cells Sildenafil is a worse inhibitor of PDE6 in S than it is in M and L cone cells

Question 114 Blood 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? Progressive loss of color vision around the focal point Progressive loss of peripheral vision (both color and black/white) Progressive loss of color peripheral vision Progressive loss of black and white vision around the focal point Progressive loss of all vision at the focal point

Question 114 Blood 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? Progressive loss of color vision around the focal point Progressive loss of peripheral vision (both color and black/white) Progressive loss of color peripheral vision Progressive loss of black and white vision around the focal point Progressive loss of all vision at the focal point

Question:

Question:

Various colorblindnesses

Question 115 The 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? 0% 25% 50% 75% 100%

Question 115 The 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? 0% 25% 50% 75% 100% Dad: XR Y Mom: 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” So do some women! (red and green opsin genes are on X chromosome) – can be mosaic for different iodopsins Mantis-shrimp have 20!

Melanopsin! (just for fun) Found in ‘’intrinsically photosensitive retinal ganglion cells” (ipRGCs) Absorb blue/violet light, ~460nm Modulate circadian rhythm and 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 Rhodopsin found 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!