Neurobiology of vision

Question 1

What is the embryological origin of the retina?

Answer 1

The prosencephalon (primary brain vescile) develops into secondary brain vesicles the telencephalon and the diencephalon.
From the diencephalon the optic vesicles develop these eventually develop into the retina.

Question 2

What is the embryological origin of the lens of the eye?

Answer 2

Develops from the lens placode - an ectodermal thickening

Question 3

How does the embryological development of the lens and the retina overlap?

Answer 3

The optic vesicles develop into the optic cup.
The communicates via reciprocal FGF signalling with the lens (developing from the otic placode)
Thise results in a coordinated signal to growth, divide and morphologenesis to form the mature eye.

Question 4

What is the important homeobox transcription factor in the eye?

Answer 4

Pax6

Question 5

What is the importance of Pax6 in the embryological development of the eye?

Answer 5

Is a homeobox transcription factor
Regulates genes involved in the embryological development of the eye.
If mutated - no eye development
If expressed in abnormal regions - eye develops in unusual anatomical region.

Question 6

How is Pax6 role in the embryological development of the eye important clinically?

Answer 6

Homozygous mutation is not compatible with life
Heterozygous mutation is compatible with life but leads to congenital aniridia. This can be variable iris hypoplasia such as complete aniridia with subscapular anterior cataracts or iris pseudocoloboma,

Question 7

What are the five principle neuronal cell types found in the neural retina?

Answer 7

The photoreceptors (rods and cones)
Bipolar cells
Horizontal cells
Amacrine cells
Retinal ganglion cells

Question 8

What is the function of photoreceptors in the retina?

Answer 8

Convert light into electrical information (not action potentials).

Question 9

What is the role of horizontal and amacrine cells in the retina?
(simple overview)

Answer 9

Provide lateral inhibition to photoreceptors and bipolar cells respectively via central surround functional organisation pathways.

Question 10

When can the term action potential be used when taking about retinal circuits?

Answer 10

Only retinal ganglion cells can generate action potentials
The rest of the circuitry generates information in the form of subtle changes in hyperpolarisation and depolarisation of the membrane potential.

Question 11

How do retinal ganglion cells communicate to the brain?

Answer 11

Project axons across the internal surface of the retina and send signals down the optic nerve to the brain.

Question 12

How does the presence of light generate an electrical change in photoreceptors?

Answer 12

Rods = rhodospin = opsin and chromophore
Cones = photopsin = opsin and chromophore

Photon of light causes isomerisation of 11-cis-retinal (the chromophore) to all-trans-retinal.
This results in a conformational change of the pigment causing activation of transducin (aGPCR)

The alpha subunit causes activation of phosphodiesterase, which catalyses the breakdown of cGMP to GMP.

This results in the closure of cGMP-gated Na+/Ca2+ channels (influx) in the outer segment of the photoreceptor.
Outflux K+ channels remain open in the inner segment all the time.

PR becomes hyperpolarised.

Question 13

Where is rhodopsin located in the rod cells?

Answer 13

In the outer segment disks (folding of the membrane)

Question 14

How is the absence of light (darkness) affect the photoreceptors in the retina?

Answer 14

No isomerisation from 11-cis-retinal to all-trans retinal.
No conformational change so no activation of transducin, no activation of phosphodiesterase
Levels of cGMP remain sufficient to keep Na+/Ca2+ channels open in the outer photoreceptor segment
K+ ioin channels in the inner segment are also open for reflux but has a lesser effect than Na+ influx

Photoreceptor becomes depolarised.

Question 15

How are photoreceptors arranged on the retina?

Answer 15

Cones are most concentrated at the fovea, decrease rapidly in concentration as go outwards
Rods concentration increases steadily from the peripheral to the centre, but then decreases rapidly so as not to be present in the fovea.

Question 16

How does the ratio of rods/cones to bipolar cells effect their function?

Answer 16

Rods - <30:1 ratio meaning provide a single point of convergence on bipolar cells - able to activate in low light intensity, however have a lower visual acuity.

Cones - 1:1 ratio, maximising resolution, but are less sensitive to light, require a high light intensity

Question 17

How does evolutionary medicine/genetics link to colour blind?

Answer 17

Photoreceptor pigements in cones can be short, medium or long wavelength to detect blue, green or red wavelength of visible light.
Trichormatic vision evolved from a duplication of the ancestroal M/L opsin gene on the X chromosome.
A mutation on the x-chromosome may knock out the M L or both opsin genes.
Predispose males to colour blind.

S opsin gene is found on chromosome 7.

Question 18

What is meant by on off circuits in the retina?

Answer 18

Photoreceptor have action on both an on circuit bipolar cell and an off circuit bipolar cell.
The combined balance of changes in activity of these circuits alters the perception of light intensity.

Question 19

If glutamater is the neurotransmitter acting on both the on and off pathway bipolar cell why does it inhibit the on pathway and activate the off pathway?

Answer 19

Glutamate
Act on mGluR6 receptor - inhibitory effect - found on on circuitry bipolar cell
Act on AMPA receptors - activator effect - found on off circuitry bipolar cell.

Question 20

How does a high light intensity affect the on and off circuits in the retina?

Answer 20

Light - hyperpolarised PR - dec glutamate release
1. dec glucose at mGlur6 receptors = less inhibition of on bipolar cell = more glutamate release by bipolar cell = more activation of on-centre ganglion cell
2. dec glucose at AMPA receptors = less activation of off bipolar cell = less glutamate release from bipolar cell = less activation of off centre ganglion cell

Overall - more signals from on and less signals from off - interpret as inc light intensity.
Note RGC - pattern of action potential firing that generates the information

Question 21

How does a low light intensity affect the on and off circuitry of the retina?

Answer 21

Low light - photoreceptors are depolarised (d for dark) - more glutamate release.
1. more glutamate at mGlu6 receptors = more inhibition of on bipolar cell = less glutamate release by bipolar cell = less action potential generation in on retinal ganglion cell
2. more glutamate at AMPA receptors = more activation of off bipolar cell = more glutamate release by bipolar cell = more action potential generation on the off retinal ganglion cell

Overall inc off signal and decreased on signals - creates a dark signal.
Note RGC - pattern of action potential firing that carries information

Question 22

What is the function of the centre-surround functional organisation in the retina?

Answer 22

Horizontal cells and amacrine cells allow communication between neighbouring photoreceptors.
Cause circuits to inhibit ear other.
Increase contrast in light perception between neighbouring photoreceptors
This amplifies the differences in the visual scenes.
Results in a better than reality system.

Question 23

Describe the circuitry of the centre-surround functional organisation in the retina when central PR exposed to light. ?

Answer 23

The central PR targeted by inc light - hyperpolarised - less glutamate production.
Less activation of horizontal cell
Horixontal cell projects to neighbouring PR, less inhibition of neighbouring receptor = activation of neighbour PR.
Depolarised neighbour PR = dark visual information

In dark opposite it true, Both scenarios increase contrast between neighbouring PR.

Question 24

What is the relationship between horizontal cells and photoreceptors?

Answer 24

Horizontal cell is activated by an active PR
Horizontal cell inhibits PR.

Question 25

What is important about the organisation of topographic map on the visual cortex?

Answer 25

The visual fields (not the retina) is mapped on the visual cortex
It is mapped upside down
The left hand side of the brain contains right side of the world and vice versa.

World = 1 2 3 4 5 6 7 8
Visual cortex = upside down 5 6 7 8 1 2 3 4

Question 26

What is the pattern of retinal axon projects in the optic chiasm?
Part of primary visual circuitry.

Answer 26

Nasal axons desiccate at the chiasm
Temporal axons continue ipsilaterally.

Question 27

What is the basic function of the secondary visual cortices?

Answer 27

Interpretation of information represented on primary visual cortex.
Projections go from V1 to the secondary areas and also between secondary areas.

Question 28

What is another term for the primary visual cortex?

Answer 28

The striate cortex - as striped appearance due to large bond of myelinated axons projecting from the LGN.
or BA17.

Question 29

What are the major projection sites from the RGC?

Answer 29

The hypothalamus
The Pretecum
The superior colliculus
The striate cortex/primary visual cortex
The lateral geniculate nucleus

Question 30

What is the function of retinal ganglion cells projecting the the suprachiasmatic nucleus?
Where is this located?

Answer 30

The suprachiasmatic nucleus is a bilateral structure in the hypothalamus
Regulates arousal responsible for circadian rhythm, - sense amount of light not necessarily what light shows.

Question 31

What is the purpose of retinal ganglion cells projecting to the pretectal nucleus?
When is this located?

Answer 31

Reflex control of pupils and the lens.
Pretectal nucleus is located near the sup/inf colliculi at the junction between the midbraina nd forebrain.

Question 32

What is the neural circuitry in reflexive pupillary constriction?

Answer 32

Photoreceptors hyperpolarised in the presence of inc light intensity - results in a pattern of action potentials being generated in the on retinal ganglion cells.
This pattern of information is projected along the optic nerve and optic tract to the pretectal nucleus in the midbrain where a synapse occurs.
Projections go bilaterally to both the Edinger Westphal Nucleus responsible for the PANS function of the oculomotor nerve.
Projections to the ciliary ganglion, where synapse occurs, then to the sphincter pupillary muscle cause contraction - leading to miosis.

Question 33

What is the function of the RGCs projecting to the superior colliculus?
Where is this located?

Answer 33

Superior colliculus is responsible for co-ordinating saccadic eye movements.
Moving focus of gaze to look at a new object e.g brightly coloured or loud
Is reflexive
The superior colliculus is located in the midbrain.

Question 34

What are the different connections in the neural circuitry responsible for reflexive saccadic eye movements?

Answer 34

RGC /optic nerve
To the superior colliculus (synapse)
Projects to the horizontal gaze control centre and the vertical gaze centre to control nearby located CN3,4,6 motor nuclei.

Question 35

What is the purpose of RGCs projecting to the lateran geniculate nucleus?
Where is this nucleus located?

Answer 35

Nucleus is located in the thalamus
Is responsible for transferring visual information to the primary visual cortex for conscious proprioception.

Question 36

What are the anatomical features of the organisation of lateral geniculate nucleus?

Answer 36

Arranged in 6 layers
The nasal retina project to layers 1,4 and 6
The temporal retina project to layers 2,3 and 5.
This keeps information from different eyes separate.

Question 37

What are the different cell types found in the lateral geniculate nucleus?
What are they responsible for?

Answer 37

The P ganglion cell - conveys info regarding colour and fine spatial detail, layers 3-6
The M ganglion cell - conveys info regarding movement detection, high temporal resolution, larger recepetive field. , layers 1 and 2
The K ganglion cell - project as small intermediates between LGN layers.

Question 38

What is important about the anatomy of the thalamocortical fibres in the primary visual neural circuitry?

Answer 38

Superior retina fibres - through the parietal lobe (info on inferior visual field)
Inferior retinal fibres - through the temporal lobe (info on superior visual field)
The inferior visual field is called Meyers loop - is important to avoid in temporal lobe epilepsy surgery.

Question 39

What is the organisation of the primary visual cortex?

Answer 39

Like all cortex = split into 6 layers
All 6 layers have slightly different projection patterns in terms of output and input.

Question 40

Where do signals from the left and right eye first meet during neural circuitry from retina to the V1?

Answer 40

V1 - primary visual cortex

Question 41

Where are the different regions of the brain that the primary visual cortex can have outputs projecting to?

Answer 41

Some to other cortical areas on same side of brain
Other cortical areas on opposite hemisphere
Subcortical structures e.g striatum, superior colliculus
Thalamus

Question 42

What are the different inputs to the primary visual cortex?
What layers are they inputs going to?

Answer 42

Thalamocortical neurons project into layer 4

Brainstem modulatory systems project into all 6 layers
Other cortical areas tends to project into layer 1,2,4 and 5.

Question 43

What are the two patterns of information travel by which secondary and association visual area interpret the information from V1?

Answer 43

The dorsal stream
The ventral stream.

Question 44

What is the role of the dorsal stream in visual interpretation?

Answer 44

V1 neurons project to V2
V1 and V2 can project to the middle temporal (sometimes called V5).
Middle temporal (area of extrastriate visual cortex) projects to the parietal association cortex
Associated with movement and positional information.

Question 45

What is the role of the ventral stream in visual interpretation?

Answer 45

V1 projects to V2, to V3 to V4.
To the inferior temporal cortex.
This pathway is associated with recognition, especially of complex aspects of a visual scene.