I.

II.
III.

General principles of sensory physiology

The somatosensory System
Chemical Senses

IV.Vision
V.

Hearing and Equilibrium

Lect. univ. dr. Loredana - Cristina MEREU

Laboratory of Biophysics & Med. Physics, Faculty of Physics,
'Alexandru Ioan Cuza' University of Iasi

VISION
Studying vision provides the opportunity to explore
the brain at many different levels, from the physical and
biochemical mechanisms of phototransduction to the
boundary between psychology and physiology.
In many animals, primates in particular, more of
the brain is devoted to vision than to any other sensory
function.
This is perhaps because
of the extreme complexity of
the task required of vision: to
classify and to interpret the
wide range of visual stimuli in
the physical world.

Vision

Human visible light lies only

within the range ~380-750 nm;
The light is detected as photons* by
the retinal cells - rods & cones.

Vision

At the highest levels of processing, the cerebral

cortex extracts from the world the diverse qualities
experienced as visual perception: from motion, color,
texture, and depth to the grouping of objects, defined by
the combination of simple features.
The first steps in the process of seeing involve:
transmission and refraction of light by the optics of
the eye
the transduction of light energy into electrical
signals by photoreceptors
the refinement of these signals by synaptic
interactions within the neural circuits of the retina.

THE EYE AND THE RETINA

The Optics of the Eye Project an Inverted Visual Image on the Retina

The study of vision begins with the eye, whose

refractive properties are determined by the curvature of
the cornea and the lens behind it. These optical
elements act to focus an inverted image on the retina,
where the first stages of neural visual processing
take place.

The Eye and the retina

The curvature of the cornea is fixed, but the

curvature of the lens is adjusted by smooth muscles that
flatten the lens when they relax, thus bringing more
distant objects into focus.
The amount of light
that reaches the retina is
controlled by the iris, whose
aperture is the pupil.
The iris, which is
situated between the cornea
and the lens in the anterior
chamber
of
the
eye,
contracts at high light levels
and expands in the dark.

The Eye and the retina

DIOPTER = a unit of
measurement
of
the
refractive power of lenses
equal to the reciprocal of
the
focal
length
measured in meters.

The Eye and the retina

Dynamic changes in the refractive power of the

lens are referred to as accommodation.
When
viewing
distant objects, the lens
is made relatively thin
and flat and has the
least refractive power.
For near vision,
the lens becomes thicker
and rounder and has the
most refractive power.
These changes result from the activity of the ciliary
muscle that surrounds the lens. The lens is held in place
by radially arranged connective tissue bands (called
zonule fibers) that are attached to the ciliary muscle.

The Eye and the retina

The shape of the lens is thus determined by two

opposing forces:
the elasticity of the lens, which tends to keep it
rounded up (removed from the eye, the lens
becomes spheroidal)
the tension exerted by the zonule fibers, which
tends to flatten it.

The Eye and the retina

When viewing distant objects, the force from the

zonule fibers is greater than the elasticity of the lens,
and the lens assumes the flatter shape appropriate for
distance viewing.
Focusing on closer objects requires relaxing the
tension in the zonule fibers, allowing the inherent
elasticity of the lens to increase its curvature. This
relaxation is accomplished by the sphincter-like
contraction of the ciliary muscle.

The Eye and the retina

Because the ciliary muscle forms a ring around

the lens, when the muscle contracts, the attachment
points of the zonule fibers move toward the central axis
of the eye, thus reducing the tension on the lens.

The Eye and the retina

Unfortunately,
changes
in
the
shape of the lens
are not always able
to
produce
a
focused image on
the retina, in which
case a sharp image
can be focused only
with the help of
additional corrective
lenses
(see annex 1!).

The Eye and the retina

One of the many consequences of aging is that

the lens loses its elasticity; as a result, the maximum
curvature the lens can achieve when the ciliary muscle
contracts is gradually reduced.
Accommodation,
which is an optical
measurement
of
the refractive power
of the lens, is given
in diopters.

(D) Changes in the ability of the lens to round up (accommodate)

with age. The graph also shows how the near point (the closest
point to the eye that can be brought into focus) changes.

Spatial Orientation and the Visual Field

The visual field is that area in space perceived
when the eyes are in a fixed, static position looking
straight ahead. The monocular visual field - is that
area of space visible to one eye and is subdivided into
two halves, the hemifields:
1. A horizontal line drawn from 0 to 180 through center
of the field defines the superior & inferior hemifields.
2. A vertical line drawn
from 90 to 270 through
center point defines the
left & right hemifields,
which are often termed
the nasal and temporal
hemifields.

Spatial Orientation and the Visual Field

The monocular visual field may be further subdivided

into quadrants:
the superior and inferior nasal quadrants
the superior and inferior temporal quadrants
Contains a blind
spot - a small area
in which objects
cannot be viewed,
which is located
within the temporal
hemifield.

Spatial Orientation and the Visual Field

The monocular visual field is determined with

one eye covered.

Spatial Orientation and the Visual Field

The area of overlap of the visual field of one eye

with that of the opposite eye is called the binocular
field. All areas of the binocular visual field are seen by
both eyes.
As our eyes are angled
slightly toward the nose, the
monocular visual fields of the
left and right eyes overlap to
form the binocular visual
field (colored red).

Spatial Orientation and the Visual Field

Objects within the binocular visual field are visible

to each eye, albeit from different angles.

RETINA - a Three-layered Structure with Five Types of Neurons

The retina is composed of five principal layers:
three layers of cell bodies separated by two layers of
neural processes, dendrites and axons.

The vertebrate retina is oriented within the eye so

that light must travel through the entire thickness of the
neuropil to reach the photoreceptors.

RETINA -The Retina Is a Three-layered Structure with Five Types of Neurons

Of the three cell layers, the first is farthest from the

center of the eye and thus is called the outer nuclear
layer. It contains the cell bodies of the photoreceptors,
the rods and cones.
The next cell layer is the
inner nuclear layer, which
contains the cell bodies of the
interneurons of the retina,
both excitatory and inhibitory.
These include:
horizontal cells,
bipolar cells,
and
amacrine cells.

RETINA -The Retina Is a Three-layered Structure with Five Types of Neurons

Finally, the ganglion cell layer is home to the

retinal neurons whose axons form the optic nerve, the
sole pathway from the retina to the rest of the CNS
Interposed between the
cell body layers are two layers
of cell processes:
inner plexiform layer
and
outer plexiform layer
, which are the sites of all
interactions
between
the
neurons of the retina.

RETINA -The Retina Is a Three-layered Structure with Five Types of Neurons

Summary diagram of the cell types and connections

in the primate retina.
R, rod;
C, cone;
H, horizontal cell;
FMB, flat midget bipolar;
IMB, invaginating midget
bipolar;
IDB, invaginating diffuse
bipolar;
RB, rod bipolar;
A, amacrine cell;
P, parasol cell;
MG, midget ganglion cell.

RETINA

There are five types of

neurons in the retina:
photoreceptors
bipolar cells
ganglion cells
horizontal cells
amacrine cells
A direct three-neuron chain - photoreceptor cell
to bipolar cell to ganglion cell - is the major route of
information flow from photoreceptors to the optic nerve.

RETINA visual receptive field

As defined by H. K. Hartline in 1938, a visual receptive

field is the region of the retina which must be
illuminated in order to obtain a response in any given
fiber. In this case, fiber refers to the axon of a retinal
neuron, but any visual neuron, from a photoreceptor to
a visual cortical neuron, has a receptive field.
The definition was later extended to include not only
the region of the retina that excited a neuron, but also
the specific properties of the stimulus that evoked the
strongest response.
Visual neurons can respond preferentially to the turning
on or turning off of a light stimulus - termed on and off responses - or to more complex features, such as
color or the direction of motion. Any of these
preferences can be expressed as attributes of the
receptive field.

RETINA -Photoreceptors

The two major types of photoreceptors in the

vertebrate eye are the rods and cones. Both types of
photoreceptor have an outer segment that contains the
molecular machinery for phototransduction, an inner
segment that contains densely packed mitochondria, a
cell body that contains the nucleus and other important
organelles,
and
a
terminal
process
that
releases
neurotransm
itter.

RETINA -Photoreceptors

RETINA Photoreceptors- Functional Specialization of the Rod and Cone Systems

The two types of photoreceptors, rods and cones,

are distinguished by:
shape (from which they derive their names),
the type of photopigment they contain,
distribution across the retina,
and pattern of synaptic connections.
These properties reflect
the fact that the rod and cone
systems (the receptors and
their connections within the
retina) are specialized for
different aspects of vision.

RETINA -Photoreceptors

Rods and cones work

together to allow the visual
system to operate over a wide
range
of
luminance
conditions.

RETINA -Photoreceptors

Under scotopic conditions

when luminance levels are very low
(e.g., starlight), only the rods are
active.
As luminance levels increase
to mesopic conditions (e.g.,
moonlight), both the rods and cones
contribute to vision.
As luminance levels increase
further yet, to photopic condition
(e.g., sunlight), rod responses
saturate and only the cones
contribute to vision.

RETINA Photoreceptors- Functional Specialization of the Rod and Cone Systems

The rod system has very low spatial resolution

but is extremely sensitive to light; it is therefore
specialized for sensitivity at the expense of resolution.
Conversely, the cone system has very high
spatial resolution but is relatively insensitive to light; it is
therefore specialized for acuity at the expense of
sensitivity. The properties of the cone system also allow
humans and many other animals to see color.

The range of luminance values over which the visual system operates.

RETINA Photoreceptors- Functional Specialization of the Rod and Cone Systems

At the lowest levels of light, only the rods are

activated. Such rod-mediated perception is called
scotopic vision. Although cones begin to contribute to
visual perception at about the level of starlight, spatial
discrimination at this light level is still very poor. As
illumination increases, cones become more and more
dominant in determining what is seen, and they are the
major determinant of perception under relatively bright
conditions such as normal indoor lighting or sunlight.

RETINA Photoreceptors- Functional Specialization of the Rod and Cone Systems

The contributions of rods to vision drops out nearly

entirely in so called photopic vision because their
response to light saturatesthat is, the membrane
potential of individual rods no longer varies as a function
of illumination because all of the membrane channels
are closed.
Mesopic vision occurs in levels of light at which
both rods and cones contribute at twilight, for
example.

RETINA Photoreceptors- Functional Specialization of the Rod and Cone Systems

From these considerations

it should be clear that most of
what we think of as normal
seeing is mediated by the
cone system, and that loss of
cone function is devastating, as
occurs in elderly individuals
suffering
from
macular
degeneration.
People who have lost cone
function
are
legally
blind,
whereas those who have lost rod
function only experience difficulty
seeing
at
low
levels
of
illumination (night blindness).

RETINA Photoreceptors- Functional Specialization of the Rod and Cone Systems

Differences in the transduction mechanisms

utilized by the two receptor types is a major factor in the
ability of rods and cones to respond to different
ranges of light intensity.
For example, rods produce a reliable response to
a single photon of light, whereas more than 100 photons
are required to produce a comparable response in a
cone.
It is not, however, that cones fail to effectively
capture photons. Rather, the change in current
produced by single photon capture in cones is
comparatively small and difficult to distinguish from
noise.

RETINA Photoreceptors- Functional Specialization of the Rod and Cone Systems

Another difference is that the response of an

individual cone does not saturate at high levels of
steady illumination, as does the rod response.
Although both rods and cones adapt to operate
over a range of luminance values, the adaptation
mechanisms of the cones are more effective.
This difference in adaptation is apparent in the
time course of the response of rods and cones to light
flashes.
The response of a cone, even to a bright light flash
that produces the maximum change in photoreceptor
current, recovers in about 200 milliseconds, more than
four times faster than rod recovery.

RETINA Photoreceptors- anatomical distribution of the Rod and Cone Systems

The distribution of rods and cones across the

surface of the retina also has important consequences
for vision. Despite the fact that perception in typical
daytime light levels is dominated by cone-mediated
vision, the total number of rods in the human retina,
(about 90 million) far
exceeds the number of
cones
(roughly
4.5
million).
As a result, the
density of rods is much
greater
than
cones
throughout most of the
retina.

RETINA Photoreceptors- anatomical distribution of the Rod and Cone Systems

In the fovea, cone density increases almost 200fold, reaching, at its center, the highest receptor packing
density anywhere in the retina.
This high density is achieved by decreasing the
diameter of the cone outer segments such that foveal
cones resemble rods in their appearance. The
increased density of cones in the fovea is accompanied
by a sharp decline in the density of rods. In fact, the
central 300 m of the fovea, called the foveola,is totally
rod-free.

RETINA Photoreceptors- anatomical distribution of the Rod and Cone Systems

Because the center of our retina (the fovea)

contains very few, if any rods, we have a foveal blind
spot under very dim conditions.

Color Vision

Perceiving color allows humans (and many other

animals) to discriminate objects on the basis of the
distribution of the wavelengths of light that they reflect to
the eye.
Color vision is the ability to detect differences in
the wavelengths of light.
The human has a
trichromatic visual system,
whereby visible colors can be
created by a mixture of red,
green and blue lights.

Color Vision

Unlike rods, which contain a single photopigment,

there are three types of cones that differ in the
photopigment they contain. Each of these
photopigments has a different sensitivity to light of
different wavelengths, and for this reason are referred to
as:
blue,
green,
red
or, more appropriately:
short (S),
medium (M),
long (L)
,wavelength cones - terms
that more or less describe their spectral sensitivities.

Color Vision

Individual cones provide color information for the

wavelength of light that excites them best. In fact,
individual cones, like rods, are entirely color blind in that
their response is simply a reflection of the number of
photons they capture, regardless of the wavelength of
the photon (or, more properly, its vibrational energy).
The light absorption spectra of
the four photopigments in the
normal human retina. The
solid curves indicate the three
kinds of cone opsins; the
dashed curve shows rod
rhodopsin for comparison.
Absorbance is defined as the log value
of the intensity of incident light divided
by intensity of transmitted light.

Color Vision

The most common form of color blindness

results in a confusion of red and green shades (i.e., redgreen color blindness).
Most cases of color blindness result from an
absent or defective gene responsible for producing the
red or green photopigment:
protanopia - the lack of red
and
deuteranopia - the lack of green.

Color Vision

As these genes are located on the X chromosome,

color blindness is more common in males than in
females.

Color Blindness: John Daltons Experiment from the Grave

The chemist John Dalton was color-blind. He thought it probable
that the vitreous humor of his eyes (the fluid that fills the eyeball behind
the lens) was tinted blue, unlike the colorless fluid of normal eyes. He
proposed that after his death, his eyes should be dissected and the
color of the vitreous humor determined. His wish was honored.
The day after Daltons death in July 1844, Joseph Ransome
dissected his eyes and found the vitreous humor to be perfectly
colorless. Ransome, like many scientists, was reluctant to throw
samples away. He placed Daltons eyes in a jar of preservative, where
they stayed for a century and a half.
Then, in the mid-1990s, molecular biologists in England took
small samples of Daltons retinas and extracted DNA. Using the known
gene sequences for the opsins of the red and green photopigments,
they amplified the relevant sequences and determined that Dalton had
the opsin gene for the red photopigment but lacked the opsin gene for
the green photopigment. Dalton was a green dichromat.
So, 150 years after his death, the experiment
Dalton startedby hypothesizing about the cause
of his color blindnesswas finally finished.

Daltons eyes.

RETINA Bipolar and horizontal cells

Within the outer plexiform layer of the retina,

approximately 125 million photoreceptor cells synapse
with approximately 10 million bipolar cells. A smaller
number of horizontal cells also synapse with the
photoreceptor cells within the outer plexiform layer of the
retina.
The bipolar and
horizontal
cells
respond
to
the
glutamate released
by
the
photoreceptor cells.

RETINA Bipolar cells

Bipolar cells do not

generate action potentials and respond to
the
release
of
glutamate
from
photoreceptors with graded potentials
(i.e., by hyperpolarizing or depolarizing).
There are at least two types of bipolar cells based
on their responses to glutamate and with different
functional properties:
The off bipolar cells are depolarized by glutamate
and function to detect dark objects in a lighter
background
The on bipolar cells are hyperpolarized by
glutamate and function to detect light objects in a
darker background.
The functional importance of the on and the off
pathways can best be understood in terms of contrast.

RETINA Bipolar cells

The stimulus condition that produces a

depolarizing response from a bipolar cell is used to
name the bipolar cell type.
An off bipolar cell depolarizes when the
photoreceptors that synapse with it are in the dark.
An on bipolar cell depolarizes when the
photoreceptors that synapse with it are in the light.

RETINA Bipolar cells

Bipolar cells have concentric receptive fields.

Light directed on the photoreceptor(s) that synapse
with a bipolar cell produces a response from the
bipolar cell called the center response.
In contrast, light
directed
on
immediately
surrounding
receptors produce
the
opposite
response.

RETINA Bipolar cells

When both the center and surrounding receptor

cells are illuminated with light, the on bipolar cell
response to stimulation of the center receptors is
reduced by stimulation of the surround receptors.
Consequently, the
strongest on bipolar cell
response is produced
when the stimulus is a
light spot encircled by a
dark ring.
For the off bipolar
cell,
a
dark
spot
encircled by a light ring
produces
maximal
depolarization.

RETINA Horizontal cells

Within the outer plexiform layer,

photoreceptor cells make both presynaptic
postsynaptic contact with horizontal cells.

the
and

RETINA Horizontal cells

The horizontal cells

have large receptive fields
involving
presynaptic
(axonal) contact with a small
group of photoreceptors and
postsynaptic
(dendritic)
contact with a larger group of
surrounding photoreceptor
cells.

RETINA Horizontal cells

By controlling the responses of their center

photoreceptors (based on the responses of the
surrounding photoreceptors), the horizontal cells
indirectly produce the bipolar cell receptive field
surround effect.
The surround effect produced by the horizontal cell
is weaker than the center effect. The surround effect,
produced by the horizontal cells, enhances brightness
contrasts to produce sharper images, to make an
object appear brighter or darker depending on the
background and to maintain these contrasts under
different illumination levels.

RETINA Ganglion cells

Within the inner plexiform layer, the axon terminals

of bipolar cells (the 2 visual afferents) synapse on the
dendritic processes of amacrine cells and ganglion cells.
Most bipolar cells release glutamate, which is excitatory
to most ganglion cells (i.e., depolarizes ganglion cells).
It is the axons of the retinal
ganglion cells (the 3 visual
afferents) that exit the eye to form
the optic nerve and deliver visual
information
to
the
lateral
geniculate nucleus of the thalamus
and to other diencephalic and
midbrain structures.

RETINA Ganglion cells

The retinal ganglion

cells are the final retinal
elements in the direct
pathway from the eye to the
brain.
Because they must carry visual information some
distance from the eye, they posses voltage-gated
sodium channels in their axonal membranes and
generate action potentials when they are depolarized by
the glutamate released by the bipolar cells.
Ganglion cells also have either on or off
responses in the center of their receptive fi elds,
according to which class of bipolar cells provide their
input.

RETINA Ganglion cells

The off bipolar cell will depolarize when it is dark

on its center cones and will therefore release glutamate
when it is dark on the center of its receptive field.
This
will
result
in
the
depolarization of the retinal
ganglion cells with which the off
bipolar synapses and in the
production of action potentials
(i.e., discharges) by these
ganglion cells. Consequently,
the retinal ganglion cells that
synapse with off bipolar cells
will have off-center/on-surround
receptive fields and are called
off ganglion cells.

RETINA Ganglion cells

The on bipolar cell will depolarize when there is light on

its center cones and will therefore release glutamate
when it is light on the center of its receptive field.
This will result in the
depolarization of the retinal
ganglion cells with which the
on bipolar synapses and in
the production of action
potentials(discharges)by these
ganglion cells. Consequently,
the retinal ganglion cells that
synapse with on bipolar cells
will
have
on-center/off
surround receptive fields and
are called on ganglion cells.

RETINA Ganglion cells

The selective response of on- and off- center bipolar cells to light
increments and decrements is explained by the fact that they express
different types of glutamate receptors.
Off-center bipolar cells
have ionotropic receptors (AMPA
and kainate) that cause the cells
to depolarize in response to
glutamate
released
from
photoreceptor terminals.
In contrast, on-center
bipolar cells express a Gprotein-coupled
metabotropic
glutamate receptor (mGluR6).

Glutamate receptors. Once released from the presynaptic

terminal, glutamate diffuses across the cleft and binds onto
receptors located on the dendrites of the postsynaptic cell(s).
Two classes
of glutamate
receptors
have
been
identified:

(1) ionotropic glutamate receptors (AMPA and kainate), which

directly gate ion channels.
(2) metabotropic glutamate receptors (G-protein-coupled
metabotropic glutamate Receptor - mGluR6), which may be
coupled to an ion channel or other cellular functions via an
intracellular second messenger cascade.

RETINA Ganglion cells

The responses of on-center and off-center retinal ganglion cells

to stimulation of different regions of their receptive fields.

RETINA Ganglion cells

The receptive field properties cause ganglion cells

to fire differently depending on whether the surround of
the equiluminant target is dark or light.
Two photometrically identical
(equiluminant) gray squares
appear differently bright as a
function of the background in
which they are presented.

In short, the receptive

fields of the bipolar cells with
which the retinal ganglion
cell synapses determine the
receptive field configuration
of a retinal ganglion cell.

RETINA Ganglion cells

The retinal ganglion cells provide information

important for detecting the shape and movement of
objects. In the primate eye, there are two major types of
retinal ganglion cells that process information about
different stimulus properties:
Type M cells - the slowly adapting response of the Type P
retinal ganglion cell is best suited for signaling the
presence, color and duration of a visual stimulus and is
poor for signaling stimulus movement.
Type P cells - the rapidly adapting responses of Type M
ganglion cells are best suited for signaling temporal
variations in, and the movement of, a stimulus.
The axons of the M and P retinal ganglion cells travel
in the retina optic nerve fiber layer to the optic disc where
they exit the eye. Most of the axons travel to and terminate
in the lateral geniculate nucleus of the thalamus.

RETINA Amacrine cells

Amacrine cells synapse with bipolar cells and

ganglion cells and are similar to horizontal cells in
providing lateral connections between similar types of
neurons (e.g., they may connect bipolar cells to other
bipolar cells or may synapse with other amacrine cells.

RETINA Amacrine cells

They differ from horizontal cells, however, in also

providing vertical links between bipolar and
ganglion cells.

There are 20 or more types of amacrine cells

based on their morphology and neurochemistry.

Phototransduction - Sensory Transduction in Photoreceptors

Phototransduction occurs when photons of light
are absorbed by photopigments located in the outer
segments of photoreceptors.

Phototransduction

The photopigment contains an organic, lightabsorbing chromophore (11- cis retinal, an aldehyde of
vitamin A) coupled to one of several possible proteins
called opsins that tune the molecules absorption of
light to a particular region of the spectrum.

Phototransduction

The opsin determines the

wavelength
specificity
of
the
photopigment and has the ability to
interact with G proteins.

Rods
contain
a
single
photopigment, rhodopsin whereas
cones contain one of three cone
opsins.

Phototransduction

When the retinal moiety in the rhodopsin molecule

absorbs a photon, its configuration changes from the 11cis isomer to all-trans retinal.
This
change
then
triggers
a
series
of
alterations in the protein
component of the molecule.
The changes lead, in
turn, to the activation of an
intracellular
messenger
called transducin, which
activates
a
phosphodiesterase
that
hydrolyzes cGMP.

Phototransduction

Likely structure of rhodopsin complexed with the

G protein transducin. Rhodopsin (red) has seven
transmembrane helices embedded in the disk
membranes of rod outer segments and is oriented with
its carboxyl terminus on the cytosolic side and its amino
terminus inside the disk.
The chromophore 11-cis retinal (blue),
attached to Lys256 of the seventh helix,
lies near the center of the bilayer.
Cytosolic loops that interact with the G
protein transducin are shown in orange.
The three subunits of transducin
(green) are shown in their likely
arrangement.

Phototransduction

Likely structure of rhodopsin complexed with the

G protein transducin.

Phototransduction

Once a photon is absorbed by the photopigment in

the receptor disks, a cascade of events (see annex 2!)
occurs that ultimately affects the membrane potential of
the photoreceptor.
Rhodopsin = retinal (~vit. A)
+ scotopsin (a transmembrane protein)

Phototransduction

This cascade of events begins with the activation

of the G protein (transducin) that then activates a
phosphodiesterase that hydrolyzes cGMP (cyclic
guanosine monophosphate)
and reduces the
intracellular concentration of cGMP.
Because the outer
membrane
of
a
photoreceptor
contains
many
cGMP-gated
cation
channels,
a
decrease
in
the
intracellular concentration
of cGMP will cause the
photoreceptor
to
hyperpolarize.

Phototransduction

http://pubs.rsc.org/en/content/articlehtml/2010/pp/b9pp00134d

Phototransduction

Importantly,
photoreceptors do
not produce action
potentials,
but
rather have graded
potentials that are
modulated around a
mean level.

Phototransduction

Phototransduction

An intracellular recording from a single cone

stimulated with different amounts of light (the cone has
been taken from the turtle retina, which accounts for the
relatively long time course of the response). Each trace
represents the response to a brief flash that was varied
in intensity.
At the highest
light
levels,
the
response
amplitude
saturates (at about
65 mV).
The hyperpolarizing response is characteristic of
vertebrate
photoreceptors;
some
invertebrate
photoreceptors depolarize in response to light.

Phototransduction

Absorption of light by the photopigment in the

outer segment of the photoreceptors initiates a cascade
of events (see annex 2!) that changes the membrane
potential of the receptor, and therefore the amount of
neurotransmitter released by the photoreceptor
synapses onto the cells they contact.

Phototransduction

The
synapses
between
photoreceptor
terminals and bipolar cells (and horizontal cells) occur
in the outer plexiform layer; more specifically, the cell
bodies of photoreceptors make up the outer nuclear
layer, whereas the cell bodies of bipolar cells lie in the
inner nuclear layer.
The short axonal processes of
bipolar cells make synaptic
contacts in turn on the dendritic
processes of ganglion cells in the
inner plexiform layer.
The much larger axons of the
ganglion cells form the optic nerve
and carry information about retinal
stimulation to the rest of the CNS.

Phototransduction

In most sensory systems, activation of a receptor

by the appropriate stimulus causes the cell membrane to
depolarize, ultimately stimulating an action potential and
transmitter release onto the neurons it contacts.
In the retina, however, photoreceptors do not
exhibit action potentials; rather, light activation causes
a graded change in membrane potential and a
corresponding change in the rate of transmitter release
onto postsynaptic neurons.
Perhaps even more surprising is that shining light
on a photoreceptor, either a rod or a cone, leads to
membrane
hyperpolarization
rather
than
depolarization.

Phototransduction

In the dark, the receptor is in a depolarized state,

with a membrane potential of roughly 40 mV (including
those portions of the cell that release transmitters).
Progressive increases in the intensity of
illumination cause the potential across the receptor
membrane to become more negative, a response that
saturates when the membrane potential reaches about
65 mV.
Although the sign of the potential change may
seem odd, the only logical requirement for subsequent
visual processing is a consistent relationship between
luminance changes and the rate of transmitter
release from the photoreceptor terminals.

Phototransduction

Light increments lead to hyperpolarization and

a reduction in neurotransmitter release, whereas
light decrements lead to depolarization and an
increase in transmitter release.
As in other nerve
cells,
transmitter
release
from
the
synaptic terminals of
the photoreceptor is
dependent on voltagesensitive
Ca2+
channels
in
the
terminal membrane.

Phototransduction

Thus, in the dark, when photoreceptors are

relatively depolarized, the number of open Ca2+
channels in the synaptic terminal is high, and the rate
of transmitter release is correspondingly great;

In the light, when

receptors
are
hyperpolarized, the number
of open Ca2+ channels is
reduced, and the rate of
transmitter release is also
reduced.

Phototransduction

The relatively depolarized state of photoreceptors

in the dark depends on the presence of ion channels
in the outer segment membrane that permit Na+ and
Ca2+ ions to flow into the cell, thus reducing the degree
of inside negativity.
The probability of these channels in the outer
segment being open or closed is regulated in turn by the
levels of the nucleotide
cyclic
guanosine
monophosphate (cGMP) - as in many other second
messenger systems.

Phototransduction

Light-induced hyperpolarization of rod cells.

The membrane potential is reduced by the flow of Na+
and Ca2+ into the cell through cGMP gated cation
channels in the plasma membrane of the outer segment.
When rhodopsin absorbs light, it triggers degradation of
cGMP (green dots) in the outer segment, causing
closure of the cation channel.
Without
cation
influx through this
channel, the cell
becomes
hyperpolarized.

Phototransduction

Cyclic GMP- gated channels in the outer

segment membrane are responsible for the light-induced
changes in the electrical activity of photoreceptors.
I.n darkness, high levels
of cGMP in the outer segment
keep the channels open.
In the light, however,
cGMP levels drop and some of
the channels close, leading to
hyperpolarization of the outer
segment
membrane,
and
ultimately the reduction of
transmitter release at the
photoreceptor synapse.

Phototransduction

In the dark, cGMP levels in the outer segment are high;

this molecule binds to the Na+ - permeable channels in the
membrane, keeping them open and allowing sodium (and
other cations) to enter, thus depolarizing the cell.
Exposure to light
leads to a decrease
in cGMP levels, a
closing
of
the
channels,
and
receptor
hyperpolarization.

the same scheme applies to cones

Phototransduction

The hydrolysis by phosphodiesterase at the

disk membrane lowers the concentration of cGMP
throughout the outer segment, and thus reduces the
number of cGMP molecules that are available for
binding to the channels in the surface of the outer
segment membrane, leading to channel closure.

Phototransduction

Transduction of stimulus energy into neural activity

by photoreceptors requires intracellular second
messengers.

1.The outer segment of both photoreceptors contains the photopigment rhodopsin,

which changes configuration when it absorbs light. 2. Stimulation of the chromophore by
light reduces the concentration of cGMP in the cytoplasm. This hyperpolarizes the
photoreceptor by closing cation channels, decreasing the transmitter released by the
photoreceptor terminals in the inner segment. 3. Receptor currents evoked by light
flashes.

 Circuitry
responsible
for
generating
receptive
field center
responses
of retinal
ganglion
cells.

Photoreceptor synapses with off-center bipolar cells are called sign-conserving (+), since the
sign of the change in membrane potential of the bipolar cell (depolarization or hyperpolarization)
is the same as that in the photoreceptor.
Photoreceptor synapses with on center bipolar cells are called sign-inverting (-) because the
change in the membrane potential of the bipolar cell is the opposite of that in the photoreceptor.

Phototransduction

One of the important features of this complex

biochemical cascade initiated by photon capture is that
it provides enormous signal amplification.
It has been estimated that a single lightactivated rhodopsin molecule can activate 800
transducin molecules, roughly eight percent of the
transducin molecules on the disk surface.
Although each transducin molecule activates
only one phosphodiesterase molecule, each of these
is in turn capable of catalyzing the breakdown of as
many as six cGMP molecules.

Phototransduction

As a result, the absorption of a single photon by a

rhodopsin molecule results in the closure of
approximately 200 ion channels, or about 2% of the
number of channels in each rod that are open in the
dark. This number of channel closures causes a net
change in the membrane potential of about 1 mV.
Equally important is the fact that the magnitude of
this amplification varies with the prevailing levels of
illumination, a phenomenon known as light adaptation.
At low levels of illumination, photoreceptors are
the most sensitive to light. As levels of illumination
increase, sensitivity decreases, preventing the receptors
from saturating and thereby greatly extending the range
of light intensities over which they operate.

Phototransduction

Despite
its
peripheral location, the
retina or neural portion
of the eye, is actually part
of the central nervous
system.
Consistent with its status as a full-fledged part of
the CNS, the retina comprises complex neural circuitry
that converts the graded electrical activity of
photoreceptors into action potentials that travel to
the brain via axons in the optic nerve.

Central Visual Pathways

Information supplied by the retina initiates
interactions between multiple subdivisions of the brain
that eventually lead to conscious perception of the visual
scene, at the same time stimulating more conventional
reflexes such as:
adjusting the size of the pupil,
directing the eyes to targets of interest,
and
regulating homeostatic behaviors that are tied to
the day/night cycle.

Central Visual Pathways

The parallel processing of different categories of

visual information continues in cortical pathways that
extend beyond primary visual cortex, supplying a variety
of visual areas in the occipital, parietal, and temporal
lobes.
Visual areas in the temporal lobe are primarily
involved in object recognition, whereas those in the
parietal lobe are concerned with motion.
Normal
vision
depends
on
the
integration of information
in all these cortical areas

Central Visual Pathways

Ganglion cell axons exit the retina through a

circular region in its nasal part called the optic disk (or
optic papilla), where they bundle together to form the
optic nerve.
This region of the
retina
contains
no
photoreceptors
and,
because it is insensitive
to light, produces the
perceptual
phenomenon known as
the blind spot.

Central Visual Pathways

Axons in the optic nerve run a straight course to

the optic chiasm at the base of the diencephalon. In
humans, about 60% of these fibers cross in the chiasm,
while the other 40% continue toward the thalamus and
midbrain targets on the same side. Once past the
chiasm, the ganglion cell axons on each side form the
optic tract.
Central projections
of retinal ganglion
cells. For clarity, only
the crossing axons
of the right eye are
shown

Central Visual Pathways

Distinct populations of retinal ganglion cells send

their axons to a number of central visual structures that
serve different functions.
The most important projections are:
to the pretectum for mediating the pupillary light
reflex,
to the hypothalamus for the regulation of circadian
rhythms,
to the superior colliculus for the regulation of eye
and head movements,
to the lateral geniculate nucleus for mediating
vision and visual perception (most important of all).

Central Visual Pathways

The circuitry responsible for the pupillary light reflex.

This pathway includes bilateral projections from

the retina to the pretectum and projections from the
pretectum to the Edinger-Westphal nucleus. Neurons in
the Edinger-Westphal nucleus terminate in the ciliary
ganglion, and neurons in the ciliary ganglion innervate
the pupillary constrictor muscles.

Central Visual Pathways

Visuotopic organization of the striate cortex in the right

occipital lobe, as seen in mid-sagittal view. (A) The primary
visual cortex occupies a large part of the occipital lobe. The area
of central vision (the fovea) is represented over a
disproportionately large part of the caudal portion of the lobe,
whereas peripheral vision is represented more anteriorly. (B)
Photomicrograph of a coronal section of the human striate cortex.

Visual Cortical Areas

The primary visual cortical receiving area is in the

occipital lobe. Nearly the entire caudal half of the
cerebral cortex is dedicated to processing visual
information.

(A) A lateral view of the left cerebral hemisphere. (B) A view of the medial
surface of the right hemisphere.
The primary motor cortex (i.e., the precentral gyrus), and the primary
somatosensory receiving area (i.e., the postcentral gyrus) are represented in
red and blue, respectively.

Visual Cortical Areas

The flow of visual information from the primary

visual cortex to other cortical areas depends on the type
of information being processed.
Information used to locate objects and detect their
motion is sent to more superior cortex (a.k.a. the dorsal
stream). Information necessary to detect, identify and
use color and shape information is sent to inferior
cortical areas (a.k.a., the ventral stream).

Visual Association Cortex.

Visual Cortical Areas

The responses of a "shapeform" type primary visual cortex

neuron is recorded while a light bar
is flashed on and off the screen.
For each of the frames, the
light bar has a different orientation.
The neuron displays a
preference (i.e., produces a
maximal response) for a light bar
centered and parallel to the long
axis of the receptive field.

Visual Cortical Areas

The responses of a "motion sensitive" primary

visual cortex neuron recorded in response to movement
of a light bar across the neuron's receptive field.
The neuron responds vigorously to movement in
one direction (i.e., from left to right) and poorly to
movement in the opposite direction (i.e., from right to
left). Consequently, this neuron exhibits directional
sensitivity.

Visual Cortical Areas

Stereoscopy depends on matching information

seen by the two eyes without any prior recognition of
what object(s) such matching might generate.
Looking at a plane more distant than the plane of
the surface causes divergence; looking at a plane in
front of the picture causes the eyes to converge).
An autostereogram.
The hidden figure
(three
geometrical
forms) emerges by
diverging the eyes in
this case

References:
NEUROSCIENCE: Third Edition, Dale Purves et al., 2004 Sinauer
Associates, Inc.
Fundamental neuroscience /by Larry Squire et al.3rd ed. 2008,
Elsevier Inc.
Lehninger_Biochemistry_4e_2005_Acrobat_60
EBooks - Chemistry - Biochemistry Garrett And Grisham 2Nd Ed
Coding of Sensory Information, Esther P. Gardner John H. Martin;
http://homepage.psy.utexas.edu/homepage/class/psy394U/hayhoe/Intr
oSensoryMotorSystems/week3/Kandel%20Ch%2021,%2022,%2023.pdf
http://cnx.org/content/m46577/latest/?collection=col11496/latest
http://neuroscience.uth.tmc.edu/s2/chapter09.html
http://downloadpdfz.com/ppt/what-is-adaptation-of-sensory-receptors
http://classes.midlandstech.edu/carterp/Courses/bio110/chap09/chap0
9.htm
http://webvision.med.utah.edu/book/part-v-phototransduction-in-rodsand-cones/glutamate-and-glutamate-receptors-in-the-vertebrate-retina/
http://highered.mheducation.com/sites/dl/free/0072437316/120060/rave
nanimation.html

Annex 1 - Vision Problems

a.
If the eyeball is too long the flat lens focuses distant objects in front of
the retina. Since light rays reflected from closer objects diverge more, and the
focal distance is longer, the focal point moves back to the retina without the lens
having to accommodate, and near vision is OK, but distant vision is blurred.
You cant flatten the lens any flatter than it already is, so youre stuck. This is
known as myopia, or nearsightedness. It can be corrected by placing a
concave lens in front of the eye, which diverges the light rays a bit before they
enter the eye. This increases the focal length and allows the relaxed lens to
focus precisely on the retina.
b.
If the eyeball is too short, the focal point from distant objects is behind
the retina, but the lens can round up to move the focal point forward, like
accommodating for near vision, and distant objects appear to be in focus. The
problem comes when objects close to the eye cause the focal length to be
longer, and the lens, which is already rounded up, cant round up any more.
This causes close objects to be blurred and is known as hyperopia, or
farsightedness. Hyperopia can be corrected by placing a convex lens in front of
the eye, which converges the light rays a bit before they enter the eye. This
decreases the focal distance so the lens can focus distant objects without
rounding up and can round up enough to focus near objects.

Annex 1 - Vision Problems

c.
A normal part of the aging process is loss of elasticity by the lens,
which inhibits its ability to round up and focus on close objects. This agerelated farsightedness in an eye with a perfectly good shape is called
presbyopia (old vision) and usually begins to be noticed around 40 years of
age. Presbyopia can also be treated with convex lenses, but since the focal
length is normal this correction will cause distant vision to be blurred, so people
commonly wear half glasses in order to be able to look over them at distant
objects and peer down through them at close objects. This makes negotiating
stairs a challenge, especially if someone was myopic to begin with and must
then wear bifocals (Think about it).
d.Astigmatism results from the surface of the lens or cornea being uneven,
which causes light to be focused on the retina in lines rather than as a single
point.
e.Cataracts are clouding of the lens due to damage from things like ultraviolet
rays, cigarette smoke, and other toxic things. The lens eventually becomes
so clouded that a person with cataracts is functionally blind even though the
photoreceptors are fine. To correct cataracts the lens can be removed and
replaced with an artificial lens.
Obviously the artificial lens cant
accommodate for close vision so it has to be preset for one or the other and
supplemented with contacts or glasses.

Annex 2
Rhodopsin is a G-Protein coupled receptor
light

Rhodopsin
about 109 rhodopsin
molecules and about
108 G-protein molecules
per rod outer segment (ROS)

photoactivated rhodopsin
(Rh*) forms in about 1 ms
and serially activates 100 to
1000 Transducin molecules
per second

Rh*

Transducin is a
heterotrimeric
G protein
specific to vision

T + T

GDP

GTP

Annex 2

light

Rhodopsin

Rh*

T-GDP

T-GTP + T

Effector
PDE

PDE*

cGMP
CNG Channels:

OPEN

GMP
CLOSED

Shut-off

Annex 2

Next question:
How are the activated
intermediates shut off?

light

Rhodopsin
Rh*

T-GDP

PDE

T-GTP + T

PDE*

cGMP
CNG Channels:

Transducin is inactivated
by the intrinsic GTPase
activity which
hydrolyzes GTP to GDP

OPEN

GMP
CLOSED

The intrinsic
GTPase activity of
the subunit
is regulated by a
GAP (GTPase
accelerating protein)
RGS-9

Annex 2

Signaling
cascade
Converts a microscopic stimulus
activation of a single molecule
-into a macroscopic response

Alberts et al, Mol Bio of the Cell

Annex 2

Phototransduction Cascade
as an enzymatic amplifier

light

Rhodopsin

Rh*

G - GDP

1st Stage of amplification:

200 - 1000 G* per Rh*

G*- GTP + G

Phosphodiesterase (PDE)

PDE*

2nd Stage amplification:

each PDE* hydrolyzes
~ 100 cGMP molecules.

GC*
GTP

cGMP

CNG Channels: OPEN

GMP

CLOSED

Total gain:
2 x 105 106
cGMP / Rh*

channel closure
generates
electrical signal