Vision ECE6397, Lecture 1

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Title
ECE 6304 Visual System Physiology,
Computation, and Methods
Prof. Valery Kalatsky Dept. of Electrical
Computer Engineering University of Houston
Lectures 9 - Supplement ON and OFF center
pathways and center surround organization of the
retina
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Glutamate receptor
Glutamate is the most prominent neurotransmitter
in the body present in over 50 of nervous
tissue
Types
Ionotropic ligand-gated ion channels These
are responsible for action potential initiation
but not propagation Activation opens a channel
that allows ions such as Na, K, or Cl- to flow.
Metabotropic do not form an ion channel
pore Indirectly linked with ion-channels through
signal transduction mechanisms. Activation leads
to a series of intracellular events that also
results in ion channel opening but must involve a
range of second messenger chemicals.
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Ionotropic vs Metabotropic
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NMDA receptor
There are many specific subtypes of glutamate
receptors, and it is customary to refer to
primary subtypes by a chemical which binds to it
more selectively than glutamate.
The primary glutamate receptor is specifically
sensitive to N-Methyl-D-Aspartate (NMDA), which
causes direct action of the central pore of the
receptor and depolarizes the neuron.
Depolarization will trigger the firing therefore
NMDA is excitatory. Activation of NMDA receptors
results in the opening of an ion channel that is
nonselective to cations. This allows flow of Na
and small amounts of Ca2 ions into the cell and
K out of the cell
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Ionotropic Glu receptors
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Metabotropic glutamate receptors mGluRs
The metabotropic glutamate receptors, or mGluRs,
are a type of glutamate receptor which are
active through an indirect metabotropic process.
They are members of the group C family of
G-protein-coupled receptors, or GPCRs. Like
all glutamate receptors, mGluRs bind to
glutamate, an amino acid that functions as an
excitatory neurotransmitter.
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mGluRs
With the exception of the mGluR6 isoform,
group-II and group-III receptors are widely
distributed in the CNS. The mGluR6 isoform is
unique to the visual system, where it is
precisely targeted to the dendritic tips of
On-bipolar cells in the retina (Nomura et al.,
1994 Vardi et al., 2000).
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So which mGluR?
So, which is the receptor located on ON-bipolar
cell dendrites? MGluR4, 7, and 8 expression has
been observed in both the inner nuclear layer
and the ganglion cell layer (Duvoisin et al.,
1995, Hartveit et al., 1995) suggesting these
mGluRs are associated with more than one cell
type. In contrast, mGluR6 expression has been
localized to the INL (Nakajima et al., 1993,
Hartveit et al., 1995) and the OPL (Nomura et
al., 1994) where bipolar cell somata and
dendrites are located. Furthermore, ON-responses
are abolished in mice lacking mGluR6 expression
(Masu et al., 1995). These mutants also display
abnormal ERG b-waves, suggesting an inhibition
of the ON-retinal pathway at the level of bipolar
cells (Masu et al., 1995). Taken together, these
findings suggest the APB receptor on ON-bipolar
cells is mGluR6.
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Parallel processing
The photoreceptors in the retina produce a point
by point representation of the visual field. At
each point, changes in the light intensity are
encoded as graded polarizations in the membrane
potential, with increases in light intensity
hyperpolarizing photoreceptors and suppressing
glutamate release. The second order neurons,
bipolar cells, receive the photoreceptor signals
through glutamate receptors in their dendrites.
There are 10 (11?) distinct morphological and
functional classes of bipolar cells representing
10 parallel neural images of the visual field.
These can be divided into two broad groups
according to the sign of their responses.
Off-bipolar cells produce excitatory signals
when the local light intensity is lower than the
mean or background intensity. On-bipolar cells
produce excitatory signals when the local light
intensity is higher than background. This
functional difference arises by virtue of the
glutamate receptors expressed within the
dendrites of the On- and Off-bipolar cells, and
the integrity of these pathways is maintained
throughout the visual system.
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Bipolar cells
Off-bipolar cells express ionotropic glutamate
receptors (iGluR). The iGluRs in Off-bipolar
cells are excitatory non-selective cation
channels. On-bipolar cells express metabotropic
receptors (mGluR). mGluR6 receptor, which is
coupled to an excitatory cation channel, in
contrast to iGluRs, closes the channel.
mGluR6 receptors mediate an inhibitory response
to glutamate, which provides the synaptic
sign-inversion required to change the
light-evoked hyperpolarization of photoreceptors
into an excitatory, depolarising response in
On-bipolar cells. All On-bipolar cells express
the same mGluR6 receptor. The biochemical
cascade that links mGluR6 receptor activation to
channel gating is poorly understood, and the
molecular identity of the cation channel is
unknown.
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More about bipolar cells
The bipolar cells then transmit the signals from
the photoreceptors or the horizontal cells, and
pass it on to the ganglion cells through
localized graded potentials. They can synapse
with either rods or cones (but not both), and
they also accept synapses from horizontal cells.
There are 10 distinct forms of cone bipolar
cells and only one rod bipolar cell Cone bipolar
cells can be categorized into two different
groups, ON and OFF Rod bipolar cells are neither
ON or OFF, but through the AII amacrine cell can
selectively excite cone ON bipolar cells (via
gap junctions) and inhibit cone OFF bipolar
cells (via Gly inhibitory synapses.) OFF bipolar
cells synapse in the outer layer of the IPL of
the retina, and ON bipolar cells terminate in
the inner layer of the IPL.
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Even more about bipolar cells
Diffuse bipolar cells (DB1DB6) contact,
non-selectively, between 5 and 10 L- and M-cone
pedicles. Some DB cells also contact S-cone
pedicles. Flat midget bipolar (FMB) cells
contact a single L- or M-cone and carry a
chromatic OFF signal. (FMB cell connected to
S-cone pedicles has been described).
Invaginating midget bipolar (IMB) cells contact
a single L- or M-cone and carry a chromatic ON
signal. Blue cone bipolar (BB) cells
selectively contact 15 S-cone pedicles and carry
an S-cone ON signal. Rod bipolar (RB) cells
contact between 6 rod spherules (at the fovea)
and 40 (in the periphery) and carry a scotopic
ON signal.
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Horizontal cells
Horizontal cells are the laterally
interconnecting neurons in the OPL of the
retina. They help integrate and regulate the
input from multiple photoreceptor cells. Among
their functions, horizontal cells are responsible
for allowing eyes to adjust to see well under
both bright and dim light conditions.
There are three basic types of horizontal cells,
designated HI, HII and HIII. HCs are thought to
be inhibitory interneurons releasing GABA.
Their arrangement together with the on-center
and off-center bipolar cells that receive input
from the photoreceptors constitutes a form of
lateral inhibition, increasing spatial resolution
at the expense of some information on absolute
intensity. The eye is thus more sensitive to
contrast and differences in intensity.
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Amacrine cells
Amacrine cells (AC) are interneurons in the
retina. Amacrine cells are responsible for 70
of input to retinal ganglion cells (RGC). BCs
(responsible for the other 30 of input to RGCs)
are regulated by ACs.
There are about 40 different types of amacrine
cells, most lacking axons. Like horizontal
cells, amacrine cells work laterally affecting
the output from bipolar cells, however, their
tasks are often more specialized. Each type of
amacrine cell connects with a particular type of
bipolar cell, and generally has a particular type
of neurotransmitter. One such population, AII,
'piggybacks' rod bipolar cells onto the cone
bipolar circuitry. It connects rod bipolar cell
output with cone bipolar cell input, and from
there the signal can travel to the respective
ganglion cells. Most are inhibitory using either
GABA or glycine as neurotransmitters.
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Inner Plexiform Layer
b) A cone pedicle, the synaptic terminal of
cones. Four presynaptic ribbons are apposed to
the invaginating dendrites of horizontal cells
(yellow) and ON cone bipolar cells (blue). This
synaptic arrangement is called a 'triad'. OFF
cone bipolar cell dendrites form contacts at the
cone pedicle base (purple).
c) A rod spherule, the synaptic terminal of rods.
The presynaptic ribbon is apposed to the
invaginating axons of horizontal cells and the
dendrites of rod bipolar cells. OFF cone bipolar
cell dendrites form contacts at the base.
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Outer Plexiform Layer
d) The axon terminal of a cone bipolar cell
(blue) contains up to 50 presynaptic ribbons,
and connects to postsynaptic amacrine cell
processes (orange) and RGC dendrites (purple).
e) A magnified view of a bipolar cell ribbon
synapse (blue) with an amacrine cell process
(orange) and an RGC dendrite (purple). The
amacrine cell provides a feedback synapse onto
the bipolar cell. This synaptic arrangement is
called a 'dyad'. Amacrine cells also form
numerous conventional synapses throughout the IPL
with RGCs and other amacrine cells (not shown).
Some amacrine cell processes reach out to the
OPL and there they provide synaptic contacts
(interplexiform processes).
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Parallel Pathways
The 'classical' pathways ON1 and OFF1.
In the ON1 pathway, rods are hyperpolarized by
light and transfer their signals onto the
invaginating dendrites of rod bipolar (RB) cells.
RB cells express the glutamate receptor mGluR6,
causing a sign inversion at the synapse (red
arrow). RB cells are therefore depolarized by
light. They transfer their signal through a
glutamatergic (AMPA) synapse (green arrow) onto
AII amacrine cells. AII amacrine cells make gap
junctions (electrical synapses expressing
connexin-36) with the axons of ON cone bipolar
cells, which in turn synapse (green arrow) with
ON ganglion cells. In the OFF1 pathway, the
pathway from rods to AII cells is identical to
ON1, but the output of AII cells differs. They
make inverting, glycinergic synapses (red arrow)
with the axons of OFF cone bipolar cells, which
in turn synapse (green arrow) with OFF ganglion
cells.
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Parallel Pathways
In the ON2 pathway, the rod signal is transmitted
to the cone pedicle through gap junctions
(expressing connexin-36) and then follows the
cone pathway to the ON ganglion cells. The
OFF2 pathway is comparable with that of ON2 to
the OFF ganglion cells. In the OFF3 pathway, OFF
cone bipolar cells make direct synaptic contacts
with the base of rod spherules and transfer this
signal directly onto OFF ganglion cells. These
pathways can be pharmacologically dissected and
the recent availability of a connexin-36-knockout
mouse has shown that different pathways operate
under different lighting conditions
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Center surround receptive filds
Light ?Cone Glu ?
Light ? Cone ? On-bipolar ? Light ? Cone ?
Horizontal ? Horizontal ? On-bipolar
? Cumulative On-bipolar ??0
Light ? Cone ? On-bipolar ? Dark ? Cone ?
Horizontal ? Horizontal ? On-bipolar
? Cumulative On-bipolar ? ?
Dark ? Cone ? On-bipolar ? Light ? Cone ?
Horizontal ? Horizontal ? On-bipolar
? Cumulative On-bipolar ? ?
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