Quiz 3 - Neural Circuits Flashcards by sophie courville

In what ways is the eye similar as a camera? (Which structures correspond to what?)

Inversion of image by the lens
Focus = contraction of lens by ciliary muscle
Film = photo-receptors in retina
Aperture/diaphragm = iris
USB port = optic nerve

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What corresponds to the pixels of a camera in the eye?

Photoreceptors :
Cones = day light and color vision
Rods = star light vision (more present in outter sheet of the retina)

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What is the resolution of photoreceptors?

100 mega-pixels

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What is the sensor of the eye and its parts?

Rhodopsin = Opsin + Retinal
Opsin = transducer (7 trans-membrane protein, G-protein coupled receptor)
Retinal = the sensor (11-cis at rest, all-trans when striked by a photon, Opsins ligand)

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What is the structure of a Rod?

The photon enters by the synaptic terminaln (outside terminal)
Inner segment (with the sooma, mitochondrias, etc.)
Outer segment (Discs containing Rh + transduction machinery)
*Photons must pass through entirety of retina before reaching discs

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What is the structure/ the components of a disc?

They all share the same cytoplasm (same rod cell)
Each have their own lumen and their own plasma membrane
At surface, Rhodopsin
+ other proteins involved in transduction cascade

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What is Retinal composed of?

Retinal = Vitamin A

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Does Rhodopsin have equal sensitivity to all the photomagnetic spectrum?

No, highest absorption = green-yellowish
lowest absorption = red
Blue = 0.5

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What is the Quantum Efficiency?

The fraction of absorbed photons that cause thodopsin to activate (isomerize retinal)
For rhodopsin = 2/3 (very sensitive photo pigments)
Photographic film = 1/10

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What are the different sources of loss of photons when entering the eye?

2.5% reflected at cornea
9% scattered in anterior compartment
Some photons pass right through the retina without being absorbed in any discs

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Why does the eye saccades?

Stimulate different photoreceptors every 0.1s bc photoreceptors are bleached by light so use new ones until they regenerate (stabilizes our view)

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Explain the 5 steps of the transduction cascade.

Photon is absorbed → Rhodpsin activates (11-cis to all-trans)
Rhodopsin binds to G protein transducer
Binding causes exchange of GDP → GTP
GTP-bound transducin’s alpha subunit freed → goes on to bind cG phosphodiesterase (PDE)
Turned on cG phosphodiesterase (PDE) chews up cGMP → GMP
Concentration of cGMP required to bind ion channels goes down so channels close
Photoreceptor is hyperpolarized (K+ still goes out, but Na+/Ca+ can’t come in)

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How long does Rhodopsin stay activated when it changes conformation?

100 ms
So shutter time of our camera is 100ms

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How does the relative amount of disc proteins influence transduction?

100% Rhodospins
12.5% tranducins G-proteins
2% phosphodiesterases

So transducin and PDE are always saturated even when small amount of Rh are activated

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How many cGMPs are hydrolysed for every Rhodopsin activated (1 photon absorbed)?

1 Rh* = 700 G proteins/transducins alpha = 1400 cGMP hydrolysed

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What is the equation to calculate % CG channels open depending on #CH hydrolysed?

% CG channels open = [1 - CG hydrolysed/1x10^5]^3

To find the amount that were closed due to photon, do 1-% CG channels open (to find current induced)

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What direction is the photocurrent?

Outward (K+ goes out) → Hyperpolarizes the cell

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How does increasing light intensity influence the photocurrent?

Increase in photocurrent with increasing of light, but saturates when all cG gated channels are closed

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What does the IV curve of cGMP channels look like?
Why is it important?

Flat until approx 0mV, increases exponentially
As cell depolarizes, pores get plugged so the curve is flat → the current is only proportional to the number of photons striking
photoreceptor, independent of Vm (< -20 mV)

*mixed channel to reverses around 0

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What is the single CG channel current?

3fA or 3x10^-15A

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How many cG channels is there in a Rod?

1.14x10^4

Can rods see single photon response?

Yes, little depolarisation with 1 single photon

How many contacts do Rods make with Bipolar cells?

Each Bipolar Cell contacts with ~ 10 Rods

How to BC contact with photoreceptors

Synaptic vesicles attach to the synaptic ribbon (in the photoreceptor) and released into the synaptic cleft
When the photoreceptor hyperpolarizes, stops releasing glutamate

How do OFF BC function?

Its ionotropic Kainate receptors receive glutamate from the photoreceptors (ribbon) in the dark → allows channels to stay open → inward going current (depolarizing current) When light strikes, the stop receiving glutamate → Kainate channels close → hyper polarization bc outward current takes over "Copy Photoreceptors" **Positive current = outwards = hyperpolarizing

How do ON BC function?

Glutamate released from photoreceptor ribbon binds to metabotropic receptor (MGLUR6) → activates G-protein → closes non-selective cation channel TRPM1 → no inward current When light strikes → No glutamate → No inhibition of TRPM1 → opening of cation channels → inward current → depolarization "Inverts photoreceptors"

Why does OFF BC have a baseline current and not ON BC?

In the dark, Ribbon synapse has a resting rate of release OFF: In the dark, the cell is depolarized by glutamate binding from photoreceptors → inward current ON: 0 current in the dark bc TRPM1 are inhibited so no current

How do inputs combine each other in Bipolar cells?

Excitatory and inhibitory *potentials* sum linearly

What is the equation for current in a receptive field?

I(x) = Ipeak * e^(-(x)^2/2(R/4)^2)

Do ganglion cells respond better to well-aimed small spots or to diffuse light?

well-aimed small spots in the excitatory regions

How are Ganglion cells organized ?

In a Moosaic fashion with amacrine cells overlapping ON are on 1 layer and OFF are on another layer

Describe the receptive field of a RGC

Photoreceptor current = center Suround = amacrine cells

What is the Outer plexiform layer and the Inner plexiform layer?

Outer plexiform layer = where photoreceptors bind to BC Inner plexiform layer = where BC bind to RGC and amacrine cells *Axons of RGC join in the optic nerve

What are starburst amacrine cells?

*Has distinct dendritic morphology Can get input from wide area to detect motion Synapses onto direction selective RGCs

What do amacrine cells release?

release GABA when excited

What is Channel Rhodopsin and Normal Rhodopsin?

- Discovered in blue-green algae that could sense light - 7-Transmembrane protein (instead of being G-protein, they're ion channel) - Binds all-trans retinal → 13-cis when activated → open pore - light sensitive ion channel → spiking in response to light

What is the Quantum efficiency of Channel Rhodopsin?

Q.E = 0.5 *Also has wavelength preferences

How can pore be mutated for different uses?

Can be mutated to let different ions pass (identify bc have different E rev)

Where do the ON-RGC and OFF-RGC synapse with the PR and amacrine cells?

In the Inner Plexiform Layer ON-RGC synapse in the inner IPL OFF-RGC synapse in the outer IPL

What are the 4 main directions of the direction selective RGC?

For mvt: - Toward the ears (~10˚) - Above the head (~110˚) - Towards the nose (~190-200˚) - Towards belly (~270˚) *Not all exactly at this angle but sum up to this prefered direction

What is the shape of Starburst amacrine cell? How is its inhibition described?

nearly perfect circle-like dendritic arbor Gives assymetric inhibition to Direction Selective RGC Release of acetylcholine from Starburst cell is not symmetric everywhere

Without starburst amacrine cells, can we still have direction selectivity from RGCs?

No, destroying starbursts detroys direction selectivity

How can we find the magnitude of the response? *normalized*

(x̄, ȳ) = (sum(x)/sum (|x|), sum(y)/sum(|y|)) response = sqrt(x̄^2 + ȳ^2) θ = tan-1(ȳ/x̄)

Explain how an OFF directive RGC would differ from an ON directive BC

Surround is ON and center is OFF so the prefered direction would be the one that hits the starburst amacrine cells first

What is the Quantum Efficiency of Channel Rhodopsin?

0.5 *Also has wavelength preference

How can we know a channel is a mixed cation channel?

Its I-V curve reverses around 0

What is E rev of a Cl channel?

-80 mV (reversal point on I-V)

What is important to consider when we are expressing Channel Rhodopsin in a cell?

resting Rin changes because we are adding channels 1/Rin new = 1/Rin + 1/R of channel Rhodopsin = 1/Rin + G (single channel)*number channels added

What is the conductance of a single channel Rhodopsin?

G = 100 fS

How can we calculate the Steady-State depolarization following the addition of ChR to a membrane?

1. Calculate new resistance 2. Depending on I-V curve of ChR, find current of the channel at resting Vm 3. V = IR gives you change in Vm 4. Consider if hyper- or depolarizing

Related to Channel Rhodopsin, what do we need to do if we are given a calculated whole-cell photocurrent and Vm with the I-V curve of the ChR?

Calculate I = G*(Vm - Rev) - I being the current induced by the change in membrane resistance du to the addition of ChR - G being the total conductance of added channels = single channel conductance*#channels

When we talk about whole-cell current, what do we talk about?

It is current induced by a change in cell properties (ex: Rin)