Visual System 2: Phototransduction

Question 1

About how many rods and cones are in each eye?

Answer 1

• about 100 million rods (for vision in very dim light)
• about 5 million cones (for day-time vision)

Question 2

Describe saturation and how they differ in rods and cones.

Answer 2

• Rods saturate:
• Saturation means that as amount of light that reaches the retina is increased the rods response increases but when very moderate light levels are reached the rod reaches its maximum response
• Saturation level is quite low and at normal room light levels the rods are saturated
• Cones DO NOT saturate
• This means that most of the time your vision is based on 5% of your photoreceptors–your cones

Question 3

photoreceptors __________ in response to light

Answer 3

hyperpolarize

Question 4

Rods & Rod System (scotopic):

Answer 4

• more sensitive (amplification)
• slow (integration time: 100msec)
• saturate at high light intensity
• poor spatial resolution
• more pigment

Question 5

Cones & Cone System (photopic):

Answer 5

• less sensitive
• fast (integration time: 25 msec)
• do not saturate
• high spatial resolution
• less pigment

Question 6

Photopigments:

Answer 6

• absorption spectra:
  
  1. rods absorb most strongly in the blue-green
  2. three types of cones

Question 7

Principle of Univariance:

Answer 7

• Photoreceptors cannot register the wavelength of the photons they catch
  
  • i.e., “the output depends on quantum catch, but not upon what quanta are caught”

Question 8

Excitatory cascade:

Answer 8

• G-protein coupled receptors
• Major difference: activated by light instead of a chemical ligand

Cascade:

1. Absorption of light activates the photopigment molecule.
2. The active photopigment molecule stimulates a G-protein (called transducin) Amplification ≅ 700 within first 100 ms
3. The activated G-protein activates cGMP phosphodiesterase
4. The phosphodiesterase catalyzes the break down of cGMP. Total amplification = 1400; i.e. at peak activation a single Rh* has indirectly caused the breakdown of about 1400 cGMP molecules.
5. cGMP maintains the cGMP gated channels in an open configuration–therefore the decrease in cGMP causes the causes the channels to close.
6. Resulting fall of Na⁺ levels cause the cell to hyperpolarize. The decrease of Ca²⁺ depresses PDE activity and enhances guanylate cyclase (GC) activity, actions that counter the effects of light and increase cGMP levels in the OS

Question 9

List the diseases that affect rods:

Answer 9

1. retinitis pigmentosa
   
   • rhodopsin**, PDE, GMP gated ion channel, arrestin
2. congenital stationary night blindness (CSNB)
   
   • rhodopsin, transducin, PDE, rhodopsin kinase

Question 10

List the diseases that affect cones:

Answer 10

1. cone, cone-rod & macular degeneration
   
   • GCAP1 (guanylate cyclase activating protein), guanylate cyclase, ABCR
2. rod monochromacy
   
   • GMP gated ion channel, cone transducin
3. red/green color vision defects & blue-cone monochromacy

Question 11

**CONCEPT 1: **concept of a receptive field

Answer 11

• Every neuron that is higher order than the photoreceptors has a receptive field that is really the “field” of photoreceptors that provide input to that neuron
• By definition: receptive field of a neuron in the visual system is the retinal area (of photoreceptors) that when stimulated influences the activity of that neuron

Question 12

CONCEPT 2: All photoreceptors act in the same way in response to light

Answer 12

• HYPERPOLARIZATION
  
  • As they hyperpolarize they release less neurotransmitter.
• Thus, the action of light on photoreceptors is to turn them OFF!!!
• Consider photoreceptors to be “OFF” cells.
  
  • If it were possible to produce an extremely tiny spot of light that illuminated a single cone, that light would turn the cone off

Question 13

• Photoreceptors _____________ in a graded fashion and they _____________ in a graded fashion.
• Photoreceptors do not produce __________. The more _________ they are, the more __________ they release.
• The more __________ they are the less __________ they release.

Answer 13

• hyperpolarize and depolarize; release transmitter
• action potentials; depolarized; neurotransmitter
• hyperpolarized; neurotransmitter

Question 14

Light that is CENTERED on the photoreceptor turns it ________.

Answer 14

OFF

• Call them “OFF-CENTERED” cells

Question 15

When a cone is depolarized it releases the typically excitatory neurotransmitter _________.

Answer 15

glutamate

Question 16

**CONCEPT 3: Activity of a single cone gives rise to **two “parallel pathways”

Answer 16

• ON CENTER
• OFF-CENTER (ionotropic receptors)

Question 17

Bipolar cells: ON-CENTER

Answer 17

• Light in the CENTER of these cells receptive fields turns them ON – metabotropic:

1. “SIGN REVERSING” synapse with cones: The OFF-CENTER character of the cone output is REVERSED in SIGN to ON-CENTER.
   
   • When light goes ON in the center, it turns the cone off, releasing inhibition, turning the ON-CENTER bipolar ON
2. Invaginating contacts on to cones
3. Contacts act like classical inhibitory synapses
   
   • i. e., presynaptic neurotransmitter release by the photoreceptors tends to hyperpolarize the postsynaptic on-center bipolar cells
4. Action of light on CENTRAL photoreceptors in the receptive field of these cells is to depolarize them
   
   • Glutamate, released by photoreceptors has hyperpolarizing effect on these on-center bipolars, this is the opposite of glutamate’s usual excitatory action

Question 18

Bipolar cells: OFF-CENTER (ionotropic receptors)

Answer 18

1. flat (also called basal) contacts on to cones
2. contacts are classical excitatory synapses (These are SIGN CONSERVING synapses)
3. action of light on the central photoreceptors of the OFF-CENTER bipolar cells receptive field is to hyperpolarize the off-center bipolar cells

Question 19

What is the reason for two parallel channels for the cone system when the rod system had only one?

Answer 19

• This organization allows one channel to provide information to the ganglion cell concerning brighter than background stimuli (the ON-center channel)
• The other, darker than background stimuli (the OFF-center channel)

Question 20

Cells that bipolar cells talk to:

Answer 20

1. amacrine cells
2. ganglion cells

Question 21

amacrine cells:

Answer 21

• provide lateral connections
• many produce transient depolarizing responses

Question 22

Ganglion cells:

Answer 22

• produce action potentials
• physiological types:
• ON CENTER and OFF CENTER types
  
  • Each can have either sustained or transient responses.
  • Melanopsin ganglion cells – photosensitive!! (Newly discovered about 8 yrs ago)
• anatomical types:
  
  1. Parasol ganglion cells
  2. Midget ganglion cells

Question 23

Parasol ganglion cells:

Answer 23

• exhibit M cell behavior (about 10%)
• large cells with large receptive fields have more transient responses
• project to M (magnocellular layers of LGN)

Question 24

Midget ganglion cells:

Answer 24

• exhibit P Cell behavior (about 90%)
• smaller cells with small receptive fields have more sustained responses
• project to P (parvocellular layers of LGN)

Question 25

Why do we care about this “new” photoreceptor **(melanopsin ganglion cells)**?

Answer 25

* **Mutations** in melanopsin have been **linked to seasonal affective disorder**. * **Manipulating** the pathway (with light/drugs) can **accelerate adjustment to time zone travel**. * Introducing **melanopsin into non-photoreceptive ganglion cells renders them photosensitive**.

Question 26

**CONCEPT 4: photoreceptors are completely synaptically interconnected by inhibitory interneurons called HORIZONTAL CELLS**

Answer 26

* Laterally interconnect the **cones with other cones** and the **rods with other rods** * Thus, every cone has a **reciprocal synaptic relationship** with all of its neighboring cones.

Question 27

Describe the **inhibitory relationship of horizontal cells:**

Answer 27

**_Inhibitory relationship:_** * _When a cone is excited_ (that is **depolarized**) it **excites horizontal cells** that it synapses with * Inhibitory horizontal cells, in turn, **synapse onto neighboring cones** * _When the horizontal cells are excited_ (that is **depolarized**) they **inhibit the neighboring cones** * The action of the depolarized horizontal cells is to **hyperpolarize the cones they synapse with** * **Activity of each cone inhibits its neighbor cones** and vice versa, **each cone is inhibited by the activity of its neighbors** * **Mutual inhibition** is carried out by the horizontal cells

Question 28

1. When a **horizontal cell is depolarized** it releases \_\_\_\_\_\_\_\_\_\_. 2. The action of ______ released from horizontal cells onto photoreceptors is to __________ the photoreceptor. 3. The horizontal cells **do not produce** \_\_\_\_\_\_\_\_\_. 4. Like the photoreceptors, they ___________ in a **graded fashion** and they release their ______________ in a **graded fashion**

Answer 28

1. GABA 2. GABA; hyperpolarize 3. action potentials 4. hyperpolarize and depolarize; inhibitory transmitter

Question 29

If we could produce a tiny ring of light that was dark in the center, so that our **cone was in the dark but the cones immediately SURROUNDING it were illuminated**, what would happen and why?

Answer 29

**Light surrounding** the cone would turn it **ON:** 1. Cones depolarize in the dark, thus, darkness turns photoreceptors ON 2. Light falling on the surrounding cones turns them OFF * releases the inhibitory action that the surrounding cones have on the central cone that is in the dark * **"ON-SURROUND"**

Question 30

What does **"ON-SURROUND"** mean?

Answer 30

* **Light falling** in the region **SURROUNDING** the photoreceptor, but **not directly on it**, turns the photoreceptor **ON**

Question 31

**Rod Monochromacy:**

Answer 31

* **Rare hereditary** condition that is due to the **absence of cone-based vision** in the eye * Rod monochromats **experience photophobia: ** * **Glare in bright conditions that is so blinding they seek to avoid it** * Since rods are responsible for seeing in low illuminations * Might be like **emerging from a darkened theater into bright sunlight** * The absence of cones also means that: * **acuity is very poor** - at its best, approximately **20/200** * poor fixation * nystagmus * visual field defects (namely a **central scotoma** due to impaired cone function) * serious refractive errors (especially **myopia**).

Question 32

What is a potential cause of rod monochromacy?

Answer 32

* Caused by mutations in CNG channel subunits or GNAT2 (**cone transducin**) * Cones are **unable to hyperpolarize in response to light**

Question 33

Red-Green Dichromacy:

Answer 33

* Individuals are able to match all colors using only **two primaries** rather than the normal three * Dichromats are **missing the function of one of the three cone types** * The **three types of dichromacy:** named according the cone photopigment that is missing 1. **protanopia** 2. **deuteranopia** 3. **tritanopia **

Question 34

How is red-green dichromacy inherited?

Answer 34

* **Protanopia and deuteranopia are sex-linked** * Inherited **recessively through the L/M gene array** located on the X chromosome * **Males** (XY): * **Will manifest** the deficiency because they have **only one X chromosome** * **Females** (XX): * Will be **color deficient only if the deficiency is carried on both X chromosomes** * Can pass the condition onto their male offspring without being color deficient themselves

Question 35

Congenital color vision defects:

Answer 35

* Present **at** **birth** * Type and severity is the **same throughout life** * Type can be **classified precisely** * **Both eyes equally affected** * **Visual acuity is unaffected** * Predominantly **protan or deutan** * **Higher incidence in males**

Question 36

Acquired color vision defects:

Answer 36

* Onset **after birth** * Type and severity can **fluctuate** * Type not easily classified – **combined defects** * **Monocular differences** often occur * **Visual acuity is often reduced** * Predominantly **tritan** * **Equal incidence in males/females**