Non-Visual Pathway - Visual Neurophysiology and Perception Spring 2026

No -- VAs only assess a small portion of vision near the central VF

Is vision just VAs?

Yes -- this is evident by the anatomical projections of the RGCs to different areas of the brain

Does the optic nerve do MORE than just relay visual signals?

-involved in visual attention, hand reaching tasks?

-filters out distracting stimuli to focus on stimulation of interest

What is the function of the pulvinar?

saccade generation; coordinates head, neck and eye movements to help direct them to the visual stimuli

What is the function of the superior colliculus?

-emotion, pain processing, learning (affected in depression)

-thought to play a role in mediating reflex avoidance to a threat captured in vision

What is the lateral habenula?

The Streams (Pic)

The Streams (Pic)

sleep regulation

Non-LGN Targets of RGC Axons

What is the function of the ventrolateral pre-optic nucleus?

synchronizing the circadian rhythm

Non-LGN Targets of RGC Axons

What is the function of the suprachiasmatic nucleus?

pupillary light reflex

Non-LGN Targets of RGC Axons

What is the function of the pretectum (olivary pretectal nucleus)?

bilaterally

Neurons from the pretectum project _______

the E-W nucleus

Where do the neurons from the pretectum project to?

they synapse in the ciliary ganglion (parasympathetic center)

Where do the neurons from the E-W nucleus go?

on the iris constrictor muscle of each eye

Neurons from the ciliary ganglion will synapse where?

true

True or False:

Light shone in one eye will stimulate pupil constriction in both eyes

pattern vision

the human visual system's capability to detect and interpret shapes, lines, and orientations, primarily processing relative light intensities and colors rather than absolute intensity

info regarding environmental brightness -- "irradiance detection"

In addition to the role in vision, the eye provides the brain with what?

the pupil size and our body's circadian rhythm

Irradiance information is used to regulate what?

patterns of physiology and behavior that have a period of roughly one day

What is a circadian rhythm?

patterns of physiology and behavior that have a period of LESS THAN ONE DAY

Ultraradian cycle

patterns of physiology and behavior that have a period of MORE THAN 1 DAY

Infraradian cycle

-Triglycerol

-Subjective alertness

-Melatonin level

-Core body temp

What are the examples given of major circadian rhythms driven by the internal clock of the body?

-fatigue during the day

-inability to fall asleep

-increased irritability and HAs

-digestive issues

-decreased ability to concentrate

What are the symptoms of "jet lag" and crossing time zones w/ disrupted circadian rhythms?

you are suddenly expected to be awake when you are usually still asleep creating a disconnect between the external time and the body's internal time

What is the issue with jet lag?

Yes -- ~1 day per time zone crossed

Will both the external time and body's internal time resynchronize after some time?

true

True or False:

If daily rhythms of behavior and physiology are controlled by an internal clock, the rhythms should persist under constant environmental conditions (constant darkness, stable temp)

looking at activity/rest cycle in mice under constant conditions

What was the 1st evidence for a internal clock in mammals?

locomotor

In the lab ______ activity is commonly used to monitor circadian behavior in rodents

free-running

Under constant conditions, a ~24hr _______ rhythm persists under constant conditions

Gradually (~1h earlier per day) will start running probably d/t internal clock

When lights are turned on 6 HOURS EARLIER, what do the mice do?

24h rotation of the planet is a constant for all life, so an advantage to anticipate night/day onset

What is the reason for circadian rhythm?

Yes -- we live in a world with artificial timing cues & are often shielded from the "Day Outside"

Are our internal clocks often masked and ignored?

caves/bunkers

Research on human volunteers in ____ have confirmed that humans have rhythms driven by an internal pacemaker

hypothalamus in the brain -- suprachiasmatic nucleus (SCN)

Where is the internal clock?

suprachiasmatic nucleus (SCN)

Axons from the retina project to the _____ in the hypothalamus and are likely linked to the circadian rhythm

becomes arrhythmic in constant darkness -- no longer runs in a pattern throughout the day

What happens when a lesion to the suprachiasmatic nucleus (SCN) is made in a rat?

animals DO NOT entrain to the light/dark cycle (they will free run)

With bilateral enucleation, what happens to the circadian rhythm of animals?

they DO entrain to the day/night light cycles

With complete rod/cone loss by knocking out cGMP, what happens to the circadian rhythm in mice?

No

Are rods/cones necessary for irradiance detection?

Yes -- they do not free run

Do some blind patients (w/ Leber's congenital amaurosis) appear to exhibit normal or near-normal circadian rhythm entrainment?

true

True or False:

A small population of RGCs are directly photosensitive

the RGCs that specifically project to the SCN (master clock for circadian rhythm)

What RGCs are directly photosensitive?

melanopsin photopigment

ipRGCs express what?

Not many -- 3000?

How many ipRGCs in the retina?

Yes -- when all the glutamate is blocked in the retina

Can light-evoked responses be recorded from cultured ipRGCs completely isolated from other retinal cell types?

~480nm

What is the peak spectral sensitivity of ipRGCs?

Threshold irradiance for melanopsin activation -- requires a brighter light to stimulate.

Which is higher?

Threshold irradiance for melanopsin activation or that for rod/cone stimulation. What does this mean?

Yes -- by encoding diphtheria toxin receptor with the melanopsin gene

Is it possible to genetically completely ablate ipRGCs in mice? How?

Normal vision for the patient but no circadian rhythm. Animal will react as if in the dark at all times.

"Circadian blind", not "visually blind"

What is the result of ablating ipRGCs in the retina?

true

True or False:

Since the discovery of ipRGCs, there has been a major paradigm shift in the understanding of retinal function

Pattern vision v irradiance detection

blue

Exposure to ____ light (430-480nm range) wakes us up in the morning by signaling the brain to suppress the sleep hormone melatonin and produce the hormone cortisol, which increases wakefulness

blue light (480nm)

ipRGCs are most sensitive to what color/wavelength of light?

true

True or False:

ipRGCs project to a number of non-SCN sites

No

Do ipRGCs project to the pre-optic nucleus?

sleep regulation

What are ipRGCs that project to the pre-optic nucleus involved in?

Yes

Do ipRGCs project to the SCN?

key role in regulating melatonin release from the pineal gland and promoting sleep

What are ipRGCs that project to the SCN involved in?

melatonin

Light suppresses _____ at night

blue

**supports the role of ipRGCs mediating effect of the circadian rhythm

In 2 blind patients, _____ light was effective at inhibiting melatonin

Melatonin Suppression by White Light in Healthy Subjects (Pic)

Melatonin Suppression by White Light in Healthy Subjects (Pic)

Melatonin Suppression by Blue Light in Blind Subject (Pic)

Melatonin Suppression by Blue Light in Blind Subject (Pic)

No -- they do filter out SOME small wavelength light but it is a relatively small %

Do blue light blocking filters, filter out blue light effectively?

-lack of properly controlled studies

-no convincing evidence that these coating improve contrast sensitivity, symptoms of eyestrain, or sleep quality

-no evidence to indicate that these lenses conserve macular health (prevent mac degen)

Conclusions on Blue Light Blocking Filters

blue

Electronic devices tend to have screens that are rich in the ___ spectrum

Yes

Is the intensity of light from the electronic device screens as important as the spectral properties

Between S cones and Rods

Where is the melanopsin curve located on a spectral sensitivity curve?

100

ipRGCs are ____x more sensitive to 480nm v 600nm light

blue

If blue and orange light are equally bright, the (blue/orange) light will evoke greater ipRGC stimulation

orange

if the orange light is 1000x as bright as the blue light, the (blue/orange) light will evoke greater ipRGC stimulation

true

True or False:

Relatively bright lights are needed to stimulate melanopsin

If the phone is held 10cm from eye and the room was dark and phone is at max brightness

When do smartphones suppress melanopsin at night?

pupillary light reflex

ipRGCs project to the OPN pretectum and contribute to the _____ in vivo

Yes

Can either rods/cones or ipRGCs mediate pupil reflexes?

Pupil Function in Normal Mice & Mice with Rod/Cone Function Knocked Out (Pic)

Pupil Function in Normal Mice & Mice with Rod/Cone Function Knocked Out (Pic)

Pupil Function in Mice with Melanopsin Knocked Out & Rod/Cone Function Unaltered (Pic)

Pupil Function in Mice with Melanopsin Knocked Out & Rod/Cone Function Unaltered (Pic)

Pupil Function in Mice with Melanopsin and Rod/Cone Function Knocked Out (Pic)

Pupil Function in Mice with Melanopsin and Rod/Cone Function Knocked Out (Pic)

Prolonged light responses that persist post-light offset. The spiking gradually will slow until stopping

ipRGCs exhibit what for prolonged periods of time?

worse

ipRGCs have (better/worse) temporal resolution than rods/cones

blue; red

**This is consistent with contribution from slugglish ipRGCs to blue light response

In humans, the pupil-redilation is longer with ____ light stimulation than ____ light stimulation

melanopsin

By blocking rod/cone signaling pharmacologically, post-illumination pupil response in primates is ____ related

Pupil Responses to Red Light & Blue Light (Pic)

internally

SUMMARY: Although we seem to live in a 24h society, our behaviors and physiology, like all animals, exhibits daily rhythms that are generated (externally/internally)

in the SCN in the hypothalamus

SUMMARY: Where is the central clock that regulated daily rhythms located?

blue

SUMMARY: ipRGCs are most sensitive to ____ light

signal information about ambient light levels to the SCN and play a major role in synchronizing circadian and sleep/wake rhythms

SUMMARY: What is the function of ipRGCs?

Yes

SUMMARY: Can understanding biological clocks and associated rhythms have medical implications in regards to human health and the treatment of certain diseases?

Yes

SUMMARY: Can eye diseases disrupt both pattern vision and irradiance detection in some patients?