Neurophysiology Lecture 2

Question 1

Sensory Receptors

1. What are they?
2. What are Neurotransmitter Receptors?
3. The conversion process is called what?

Answer 1

1. Specialized neurons that convert physical stimuli into electrical signals which other neurons can receive and process.
2. Proteins on the neurons (similar names, different things)
3. Transduction

Question 2

Rods and Cones

1. Similar processes are involved in rods and cones. Process is called what?
   a. Rods contain what?
   b. Cones contain RETINAL linked to what?
2. What region has REFRACTIVE PROPERTIES?
   a. RI?
   b. Funnels Light into what?
   c. Produces what?

Answer 2

1. Phototransduction
   a. Rhodopsin (retinal linked to an opsin: OPN2)
   b. other Opsins (OPN1-LW, OPN1-MW, OPN1-SW)
2. Ellipsoid Region
   a. High
   b. the Outer Segment
   c. Directional Sensitivity (Styles-Crawford EFFECT)

Question 3

Characteristics of Phototransduction

1. Light energy is converted to what?
2. A response to light requires only what?
   a. Min a Rod needs to be stimulated?
   b. Visual sensation can be produced by what?
3. How fast is the response?
   a. Potential change can occur in as little as what?
4. The Process has what kind of range?

Answer 3

1. to a Change in Electrical Potential
2. only a Small number of photons
   a. a SINGLE PHOTON
   b. by 90 photons arriving at the eye
3. RAPID
   a. as 20ms for a bright light.
4. LARGE DYNAMIC RANGE (about 10 orders of magnitude)

Question 4

Photopigments

1. They’re a combination of 2 things?
   a. Type of Opsin determines what?
   b. In rods, the photopigment is called what?
2. When 11 cis-retinal absorbs a photon, what happens?
3. What does this conversion do?

Answer 4

1. 11 cis-retinal with an OPSIN Protein
   a. wavelength sensitivity
   b. Rhodopsin
2. Converts to All Trans-Retinal (Lower Energy State)
3. changes the structure of Retinal and, thereby, the Rhodopsin Molecule

Question 5

1. What creates cGMP?
2. What converts it to GMP?
3. What converts that to GPD?
4. What happens last?

Answer 5

1. GTP gets converted to Guanylate Cyclase
2. Phosphodiesterase (PDE)
3. Nucleoside Monophosphate Kinase
4. CAC converts GPD to GTP, and cycle starts all over again.

Question 6

Cyclic Nucleotide-Gated Channels

1. What are they made of?
   a. How many domains are transmembrane?
   b. what does the other do?
2. When is the Spatial relationship b/w peptides is changed?
3. What allows the Channel to Close?

Answer 6

1. Tetramer of 4 Peptides, Each with 7 domains.
   a. 6 of the domains, and they cyclize to form a pore.
   b. the 7th (P) is the SELECTIVITY FILTER: Controls what can pass through the pore
2. by binding of the Cyclic Nucleotide, causing the channel to open
3. Removal of the Cyclic nucleotides allows the channel to close.

Question 7

At Rest

1. Dark Current: Define
   a. What enters the cell, and thru what?
   b. What maintains Na+ and Ca2+ gradients?

Answer 7

1. Cell is depolarized, and Neurotransmitter is being released
   a. Na+ and Ca2+ enter the cell thru CNG (Cyclic nucleotide-gated) ion channels kept open by cGMP, LEADING to Depolarization
   b. the Na+, Ca2+/K+ pump

Question 8

From Photon to Potential Change

1. When 11 Cis-Retinal Absorbs a photon, what happens?
   a. What do these then Interact with?
2. Alpha subunit here does what?
3. what else happens?

Answer 8

1. Converts to All TRANS-Retinal
   a. All the Trans-Retinal-containing Rhodopsin interacts with “TRANSDUCIN” (Consists of ALPHA, BETA, and GAMMA Subunits)
2. of Transducin, Exchanges its GDP for a GTP and dissociates from Beta and Gamma Subunits
3. a. Dissociated Alpha subunit activates Phosphodiesterase, causing the breakdown of cGMP
   b. cGMP-Gated channels close and the cell Hyperpolarizes
   c. Neurotransmitter Release Stops

Question 9

Inactivation of Phototransduction

1. What gets inactivated?
   a. What reduces the Activity of Rhodopsin?
   b. What further reduces its activity?
2. PDE is INACTIVATED
   a. How?

Answer 9

1. “All-Trans” Rhodopsin
   a. thru Phosphorylation by Rhodopsin Kinase
   b. Binding of Arrestin
2. a. RGS (regulator of G Protein Signaling) protein Complexes activate Transducin’s GTPase function Cleaving the Bound GTP to GDP thereby Inactivating the PDE

Question 10

Calcium Feedback

1. What decreases the Intracellular Calcium concentration?
   a. What continues to pump Calcium out?
   b. Why doesn’t Calcium enter?
2. Decreased Intracellular Calcium Levels Favor and oppose what?
   a. Reduced PDE Function: Mediated by what?

b. Increased Production of cGMP: Mediated by what?
c. Increase Sensitivity of CNG channels to cGMP: Mediated by what?

Answer 10

1. Closing of CNG Ion Gated channels.
   a. Na+, Ca2+/K+ exchanger continues to pump calcium out.
   b. No calcium enters because the Channel is Closed
2. Favor Inactivation and Oppose Re-activation
   a. Recoverin, unbinds from Rhodopsin Kinase, Activating the Kinase
   b. Mediated by Guanylate Cyclase Activating Protein (GCAP) (40ms)
   c. Mediated by Calmodulin

Question 11

Regeneration of Retinal

1. All-trans retinal is hydrolyzed from the Opsin protein as what?
   a. This gets Isomerized to what?
2. Some All-Trans Retinoic Acid is used as what?

Answer 11

1. All-Trans RETINOL
   a. to 11-cis RETINAL in the RPE (involves RPE 65 enzyme) and returned to the photoreceptor for re-use
2. as a Transcriptional Signal (there’s a constant need to also produce New Retinal)

Question 12

Renewal of Outer Segments

1. Rod’s shed Exhausted discs from where?
   a. New discs are added on from where?
2. Cones shed what?
3. Shedding has what kind of cycle?
4. Shed materials are phagocytosed by what?

Answer 12

1. From their Distal ENDS
   a. At the INNER SEGMENT JUNCTION
2. the distal parts of their plasma membranes together with Exhausted Phototransduction Elements
3. Diurnal Cycle
   a. Rod outer Segment shed at ONSET of LIGHT
   b. Cone Outer Segments shed at DUSK
4. by the RPE

Question 13

Selectivity of Cone Photopigments

1. 3 Cone photopigments
2. S
3. M
4. L

Answer 13

1. Different Opsins –> Different wavelength sensitivities
2. a. Peak absorbance at 420 nM
   b. Prefers BLUISH GREEN LIGHT
3. a. Peak at 530 nM
   b. Prefers Yellowish Green Light
4. a. Peak at 565 nM
   b. Prefers Yellow Light

Question 14

Principle of Univariance

1. a Photopigment can absorb photons of light with what?
   a. However, Peak absorbance will occur where?
2. Each Photon absorbed produces what?
3. Once a photon is absorbed, what’s lost?

Answer 14

1. with many different wavelengths
   a. at a single wavelength
2. the same effect on the photopigment (univariance)
3. information about its Wavelength

Question 15

Detecting Color

1. What’s needed to discriminate Wavelengths?
   a. How many needed to distinguish ALL Visible Wavelengths?
2. Ex: Yellow stimulates 2 things?
   a. Distinguishable from what?
3. Note: A combination of Green and Red Light would produce what?

Answer 15

1. At LEAST 2 different types of photopigments (2 different cones)
   a. 3 are needed
2. M and L Photopigments EQUALLY
   a. Distinguishable from GREEN, which STIMULATES M MORE. Distinguishable from Red, which stimulates L more
3. would produce the the same relative stimulation as Yellow.
   * Would not be distinguishable from YELLOW. BASIS for METAMERS

Question 16

Bezold-Brucke Effect

1. The perceived Hue of LIGHT changes as what changes?
   a. Below 503nm?
   b. Above 503 nm?
2. No change occurs at what?
   a. These are the peak sensitivities for what?
3. At other wavelengths, how many Cones are involved in Color Discrimination?
   a. Increasing Light intensity will have a greater effect on what?

b. If the S Cone is MORE sensitive to Increasing intensity than the M cone, then light detected by both Cones will appear more what?

Answer 16

1. as its INTENSITY Changes
   a. hues appear more blue as their intensity increases
   b. hues appear more yellow as their intensity increases
2. at Invariant Wavelengths
   a. for EACH type of Cone
3. 2 or more cones
   a. on One cone than on the other.
   b. Will appear More Blue when the Intensity is Increased

Question 17

Photopic vs. Scotopic Sensitivities

1. Scotopic: define
   a. Involves what?
   b. Acuity?
   c. Color perception?
2. Photopic: Define
   a. Involves what?
   b. Acuity?
   c. Color perception?

Answer 17

1. Vision at Low Levels of illumination
   a. Involves the RODS
   b. REDUCED
   c. NONE
2. Vision at Moderate to High Light Levels
   a. Rods and Cones
   b. High
   c. Color Vision

Question 18

Photochromatic Interval and Purkinje Shift

1. Photochromatic Interval: Define
   a. Large interval at what?
   b. Zero interval at what?
2. Purkinje Shift: Define
   a. When viewing green and Yellow lights of equal intensity, green light would appear how?

Answer 18

1. Difference in Sensitivity b/w Scotopic and Photopic vision at a Given wavelength
   a. 450 nm
   b. 650 nm
2. Relative increase in BRIGHTNESS of Longer wavelengths as lighting conditions change from Scotopic (peak sensitivity 507nm) to Photopic (Peak sensitivity 555 nM)
   a. Brighter under Scotopic Conditions, and the Yellow under Photopic Conditions

Question 19

Light Adaptation

1. Dynamic Range of illumination Intensity Covers what?
   a. Dimmest?
   b. Brightest?
2. Adaptation does what 2 things?
3. Light adaptation takes what?
4. Several Process contribute to adaptation? (5)

Answer 19

1. More than 10 orders of Magnitude
   a. 4 for rods
   b. 7 for cones
2. Reduces Photoreceptor’s Sensitivity to Light and Speeds Recovery
3. Takes Time
4. a. Calcium-dependent mechanisms
   b. Elevated PDE Activity
   c. Movement of Proteins out of Outer Segment
   d. Pigment Bleaching (Rods Only)
   e. Response Compression

Question 20

Response Compression

1. Occurs during what?
2. Sensitivity to additional illumination is DECREASED for what reason?
3. Never exceeds a factor of what?

Answer 20

1. Steady illumination
2. since part of the response capacity is already being used
3. of 2 cones

Question 21

Calcium-Dependent Mechanisms

1. Caused by what?
2. Probably affects the duration of what?
   a. Reduces duration of activity of what, and INCreases duration of activity of what?

b. May also increase the affinity of what?
3. Similar to effects to what?

Answer 21

1. Steady-State decrease in Calcium Concentration
2. of Phototransduction (from start to termination) rather than the gain
   a. of Activators; Inactivators
   b. of the CNG channels for cGMP
3. to transient decrease in Calcium during Inactivation of Phototransduction

Question 22

Elevated PDE Activity

1. What happens to PDE activity?
2. What happens to cGMP Turnover?
3. Depolarization Induced change in PDE activity becomes what?
4. Response is what 2 things?
5. Depends on Calcium?
6. How powerful is it for Adaptation?

Answer 22

1. Steady-State Increase
2. INCREASES rate of cGMP turnover
3. a small blip on a large signal
4. is FASTER and SMALLER
5. Calcium Independent
6. Most Powerful mechanism for adaptation

Question 23

Movement of Proteins

1. Occurs in what?
2. Transducin redistributes from where?
3. Reduces gain at what?

Answer 23

1. in Bright Illumination that’s Prolonged
2. from Outer Segment to the Inner Segment
3. at First Amplification Step in Phototransduction: Activation of Transducin by stimulated Rhodopsin

Question 24

Dark Adaptation

1. Curve Shows Threshold Sensitivity to what?
2. Curve is what?
   a. What adapts more rapidly?
   b. What adapts to LOWER THRESHOLDS?
3. Sensitivity increases by what?

Answer 24

1. to Light after Various Periods of Darkness
2. Biphasic at Wavelengths that Stimulates Rods and Cones
   a. Cones
   b. Rods
3. by about 10 orders of magnitude

Question 25

Mechanisms of Dark Adaptation

1. Regeneration of Photopigment
   a. This would produce only about what?
2. Dark adaptation is what to light adaptation?
   a. Response what?
   b. Calcium-Dependent mechanisms:
   c. PDE Activity?
   d. Movement of proteins into what?

Answer 25

1. a. Only about a 2x increase in sensitivity, not the 10 orders of magnitude change seen.
2. it’s the REVERSE of Light Adaptation, so some of the same processes may be involved, in reverse
   a. Response EXPANSION
   b. To increased intracellular calcium
   c. REDUCED
   d. into Outer Segment

Question 26

Disorders of Dark Adaptation

1. What diseases?
2. AMD: usually occurs before what?
3. Retinitis Pigmentosa

Answer 26

1. Retinal Degenerative Diseases
2. Usually occurs before VA Loss (age-related macular degeneration)
3. a. Deficit in early phase of rod adaptation
   b. Can be seen in patients and carriers

Question 27

Disorders of Phototransduction

1. Vitamin A deficiency
   a. Needed for production of what?
   b. Produces what 2 things?
   c. Caused by what 3 things?
   d. Also by a deficiency in what?
   e. Genetic disease?
2. Congenital Achromotopsia (ACHM)
   a. Inability to see what?
   b. Mutations that cause loss of function of what?
3. Lever’s Congenital Amaurosis and Certain Types of Retinitis Pigmentosa
   a. Vision loss?
   b. Mutations?
   c. Successfully treated with what?

Answer 27

1. a. of Retinal
   b. Night blindness and Severe Vision Loss
   c. Malnutrition or Malabsorption, or Alcoholism
   d. Zn deficiency (Zn is needed to metabolize Vit A)
   e. Hereditary Abetalipoproteinemia (malabsorption of Vit A, and other vitamins)
2. a. to see colors
   b. of CNG channels or transducin in cones
3. a. Profound vision loss
   b. in RPE 65: Can’t convert all-trans retinol back to 11-cis
   c. with RPE 65 AAV gene therapy