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Retina: Anatomy and modeling

         Hassan Nasser
     Neuromathcomp - INRIA
Context
• Presentation of two articles:
  – T. Gollisch, M. Meister: Eye Smarter than Scientists
    Believed: Neural Computations in Circuits of the
    Retina (2009).
  – Helga Kolb: How the Retina Works (2003).
• Discussion in the scope of my PhD: How to
  reproduce the retinal responses.
Visual pathways (2 min)   Eye (2 min)                Retina (5 min)




        Discussion




         3 min                Model (3 min)   Interaction between cells (7 min)
What is a Visual pathway?
- It’s a set of cells bodies and
nerves conducting impulses from
the eye to the cerebral cortex



- Reception of external images
and    transport   of    visual
information




                 Retina              Optic nerve      Visual Cortex
                                                        V1, V2…
                                   (ganglion cells)
    light
Eye

      Three different layers:

      1- The external layer, formed
      by the sclera, pupil and
      cornea.

      2- The intermediate layer,
      divided into two parts:
      anterior (iris, lens and ciliary
      body) and posterior (choroid).

      3- The internal layer, or the
      sensory part of the eye, the
      retina.
Retina




-The retina is approximately 0.5 mm thick and lines the back of the
eye.
- Optic nerve contains: RGC axons + Blood vessels
Retina
                             Absorption of light




                                                                   Light direction




All vertebrate retinas are composed of three layers of nerve cell bodies
and two layers of synapses. The retina is designed according to the life
style!. EX: Fish, Frog, Turtle have 5 types of cones  Colored vision.
•   Layers of nerve cells:
     –   Outer nuclear layer
         contains cell bodies of
         the rods and cones.
     –   Inner nuclear layer
         contains cell bodies of
         the bipolar, horizontal
         and amacrine cells.
     –   Ganglion cell layer
         contains cell bodies of
         ganglion cells and
         displaced amacrine cells
•   Layers of synapses:
     –   Outer plexiform layer (OPL)
         where connections between
         rod and cones
     –   Inner plexiform layer (IPL),
         and it functions as a relay
         station for the vertical-
         information-carrying nerve
         cells, the bipolar cells, to
         connect to ganglion cells.
About retinal cells
•   Photoreceptors.
•   Bipolar cells.
•   Horizontal Cells.
•   Amacrine cells.
•   Ganglion cells.
Photoreceptors
• 2-3 types of cones
  – Cones are concentrated in the fovea centralis.
  – 6-7 millions ("red" cones (64%), "green" cones (32%),
    and "blue" cones (2%))
  – Sensitive to colors.
  – Visual acuity.
• 1 types of Rods.
  – ~ 120 millions.
  – More sensitive (1000 times) than cones but not
    sensitive to the colors  Night vision.
Day   Night
Cones & Rods




When light is shone onto a
photoreceptor, the photoreceptor
hyperpolarizes and reduces the
release of glutamate.
Bipolar - Horizontal – Amacrine - Ganglion
The retina is:

-A photo transducer that transforms
photons to current?

-The retina is a processor to detect
image features (motion, contrast,
edges)?

-The retina is a sophisticated processor
that exceed the last two expectations?



Retina smarter than scientists believed!
More than 50 types of connected cells.



        FM Signal
Connections between retinal cells
• Introduction:
  – Synapse.
  – Action potential.
  – Graded action potential.
• Connection types:
  – Chemical synapses.
  – Electrical synapses.
(All-or-none principle)
                          Chemical Synapse




           -The action potential arrives in the Pre synaptic cells (Indicator: Increasing of
           calcium concentration inside)
           -Releasing of neurotransmitters from their vesicles in the synaptic cleft.
           -Fixation of neurotransmitters on the receptor of postsynaptic cleft.
           -Triggering of the action potential in the post synaptic cell.

      In the retina: Only RGC obeys to All-or-none principle. Others shows graded behavior
      (the postsynaptic potential is proportional to the presynaptic potential)
Electrical connections – Gap junctions




   -Allow direct and faster connection between two cells.
   -Resistance for current depends on several parameters (Acidity degree,
   Calcium concentration, temperature, …).
   -Simple model = Resistance. Complicated model: Current transfer
   taking into account the majority of parameters to produce biological
   plausibility.
Let’s see how retina works:


Connections roles in the information
 transport and parallel processing.
Synaptic connection




       Mouse retina
Gap junctions
Functional role of Gap Junction

                 - Gap junctions exists between cells of
                 every type in the retina.
                                        Stewart A et al. 2009
… Between Photoreceptors
• Blurring of visual signal.
• Reduction in acuity.

• Coupling between photoreceptors sums the
  correlated visual signal and attenuates the
  asynchronous noise which comes from photo-
  chemical transduction (improve the SNR by
  80%). Stewart A et al. 2009
… Between Ganglion cells
• Ganglion-Ganglion gap junctions (fast
  excitation < 2ms  narrow spiking frequency
  distribution).
• Ganglion-Amacrine gap junctions (slower
  connections … broad distribution).



• Synchronization of spike outputs.
The aim of my PhD is to improve the
existent retina model (VirtualRetina) in
      order to produce the retinal
 synchronized output. How? … In the
               discussion.
Circuit modeling of retinal function:
How to represent the retinal function
     in simple electrical circuits?

  • Light detection.
  • Differential motion.
Light detection




At the post-synaptic gate of photoreceptor, we have: Signal + noise.
The synaptic connection between the photoreceptors and the bipolar cell is
equivalent to: A temporal filter followed by a threshold operation.
The filtered signals are given to the bipolar cell each through a dendrite connection:
The potential in the bipolar cell will be the summation of all these signals.
Differential motion




- Coding: Making the difference between the periphery signal (fb) and the
center signal.
- Same signal  same motion. Different signal  differential motion.
Virtual Retina

           -Large scale simulation (> 10000
           cells).
           -Implementation of functional
           retinal events.
           -A       compromise       between
           computational cost and biological
           plausibility.
           -Spike       outputs   are    not
           synchronized.
Gollisch et al. 2009
How to implement the
           synchronization?
• Adding connection/Gap-Junctions between
  Ganglion-Ganglion cells and Ganglion-
  Amacrine cells.

• How to add these connection?  Study the
  statistics of real acquisition for vertebrate
  retinas.
Adding connection holds two
            possibilities


• Black box  Add connections at the level of
  ganglion cells without take into account the
  connection between Ganglion and Amacrine?

• Adding both GG and GA physical connections?
Black Box

              Rods-Cones
               Horizontal
               Amacrine
                 RGC




Adding connection between RGC: These
connection take (in a hidden way) the
connections between the RGC and
Amacrine.
Amacrine-RGC

             Rods-Cones
              Horizontal
              Amacrine
                RGC




Adding connection between RGC: These
connection take (in a hidden way) the
connections between the RGC and
Amacrine.
Center Surround Antagonism
                 -   +         -

                                   PR




                         B



                         RGC
http://news.softpedia.com/news/Con
   nections-Between-Retinal-Cell-
  Population-Mapped-159743.shtml
• “Nobody has ever seen the entire input-
  output transformation performed by complete
  circuits in the retina at single-cell resolution,”
  explains expert E.J. Chichilnisky, PhD.

  “We think these data will allow us to more
  deeply understand neuronal computations in
  the visual system and ultimately may help us
  construct better retinal implants,” adds the
  scientist.
Large scalespikingnetworkanalysis

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Large scalespikingnetworkanalysis

  • 1.
  • 2. Retina: Anatomy and modeling Hassan Nasser Neuromathcomp - INRIA
  • 3. Context • Presentation of two articles: – T. Gollisch, M. Meister: Eye Smarter than Scientists Believed: Neural Computations in Circuits of the Retina (2009). – Helga Kolb: How the Retina Works (2003). • Discussion in the scope of my PhD: How to reproduce the retinal responses.
  • 4. Visual pathways (2 min) Eye (2 min) Retina (5 min) Discussion 3 min Model (3 min) Interaction between cells (7 min)
  • 5. What is a Visual pathway? - It’s a set of cells bodies and nerves conducting impulses from the eye to the cerebral cortex - Reception of external images and transport of visual information Retina Optic nerve Visual Cortex V1, V2… (ganglion cells) light
  • 6. Eye Three different layers: 1- The external layer, formed by the sclera, pupil and cornea. 2- The intermediate layer, divided into two parts: anterior (iris, lens and ciliary body) and posterior (choroid). 3- The internal layer, or the sensory part of the eye, the retina.
  • 7. Retina -The retina is approximately 0.5 mm thick and lines the back of the eye. - Optic nerve contains: RGC axons + Blood vessels
  • 8. Retina Absorption of light Light direction All vertebrate retinas are composed of three layers of nerve cell bodies and two layers of synapses. The retina is designed according to the life style!. EX: Fish, Frog, Turtle have 5 types of cones  Colored vision.
  • 9. Layers of nerve cells: – Outer nuclear layer contains cell bodies of the rods and cones. – Inner nuclear layer contains cell bodies of the bipolar, horizontal and amacrine cells. – Ganglion cell layer contains cell bodies of ganglion cells and displaced amacrine cells • Layers of synapses: – Outer plexiform layer (OPL) where connections between rod and cones – Inner plexiform layer (IPL), and it functions as a relay station for the vertical- information-carrying nerve cells, the bipolar cells, to connect to ganglion cells.
  • 10. About retinal cells • Photoreceptors. • Bipolar cells. • Horizontal Cells. • Amacrine cells. • Ganglion cells.
  • 11. Photoreceptors • 2-3 types of cones – Cones are concentrated in the fovea centralis. – 6-7 millions ("red" cones (64%), "green" cones (32%), and "blue" cones (2%)) – Sensitive to colors. – Visual acuity. • 1 types of Rods. – ~ 120 millions. – More sensitive (1000 times) than cones but not sensitive to the colors  Night vision.
  • 12. Day Night
  • 13. Cones & Rods When light is shone onto a photoreceptor, the photoreceptor hyperpolarizes and reduces the release of glutamate.
  • 14. Bipolar - Horizontal – Amacrine - Ganglion
  • 15. The retina is: -A photo transducer that transforms photons to current? -The retina is a processor to detect image features (motion, contrast, edges)? -The retina is a sophisticated processor that exceed the last two expectations? Retina smarter than scientists believed! More than 50 types of connected cells. FM Signal
  • 16. Connections between retinal cells • Introduction: – Synapse. – Action potential. – Graded action potential. • Connection types: – Chemical synapses. – Electrical synapses.
  • 17. (All-or-none principle) Chemical Synapse -The action potential arrives in the Pre synaptic cells (Indicator: Increasing of calcium concentration inside) -Releasing of neurotransmitters from their vesicles in the synaptic cleft. -Fixation of neurotransmitters on the receptor of postsynaptic cleft. -Triggering of the action potential in the post synaptic cell. In the retina: Only RGC obeys to All-or-none principle. Others shows graded behavior (the postsynaptic potential is proportional to the presynaptic potential)
  • 18. Electrical connections – Gap junctions -Allow direct and faster connection between two cells. -Resistance for current depends on several parameters (Acidity degree, Calcium concentration, temperature, …). -Simple model = Resistance. Complicated model: Current transfer taking into account the majority of parameters to produce biological plausibility.
  • 19. Let’s see how retina works: Connections roles in the information transport and parallel processing.
  • 20. Synaptic connection Mouse retina
  • 22. Functional role of Gap Junction - Gap junctions exists between cells of every type in the retina. Stewart A et al. 2009
  • 23. … Between Photoreceptors • Blurring of visual signal. • Reduction in acuity. • Coupling between photoreceptors sums the correlated visual signal and attenuates the asynchronous noise which comes from photo- chemical transduction (improve the SNR by 80%). Stewart A et al. 2009
  • 24. … Between Ganglion cells • Ganglion-Ganglion gap junctions (fast excitation < 2ms  narrow spiking frequency distribution). • Ganglion-Amacrine gap junctions (slower connections … broad distribution). • Synchronization of spike outputs.
  • 25. The aim of my PhD is to improve the existent retina model (VirtualRetina) in order to produce the retinal synchronized output. How? … In the discussion.
  • 26. Circuit modeling of retinal function: How to represent the retinal function in simple electrical circuits? • Light detection. • Differential motion.
  • 27. Light detection At the post-synaptic gate of photoreceptor, we have: Signal + noise. The synaptic connection between the photoreceptors and the bipolar cell is equivalent to: A temporal filter followed by a threshold operation. The filtered signals are given to the bipolar cell each through a dendrite connection: The potential in the bipolar cell will be the summation of all these signals.
  • 28. Differential motion - Coding: Making the difference between the periphery signal (fb) and the center signal. - Same signal  same motion. Different signal  differential motion.
  • 29. Virtual Retina -Large scale simulation (> 10000 cells). -Implementation of functional retinal events. -A compromise between computational cost and biological plausibility. -Spike outputs are not synchronized.
  • 30.
  • 32. How to implement the synchronization? • Adding connection/Gap-Junctions between Ganglion-Ganglion cells and Ganglion- Amacrine cells. • How to add these connection?  Study the statistics of real acquisition for vertebrate retinas.
  • 33. Adding connection holds two possibilities • Black box  Add connections at the level of ganglion cells without take into account the connection between Ganglion and Amacrine? • Adding both GG and GA physical connections?
  • 34. Black Box Rods-Cones Horizontal Amacrine RGC Adding connection between RGC: These connection take (in a hidden way) the connections between the RGC and Amacrine.
  • 35. Amacrine-RGC Rods-Cones Horizontal Amacrine RGC Adding connection between RGC: These connection take (in a hidden way) the connections between the RGC and Amacrine.
  • 36.
  • 37.
  • 38. Center Surround Antagonism - + - PR B RGC
  • 39. http://news.softpedia.com/news/Con nections-Between-Retinal-Cell- Population-Mapped-159743.shtml • “Nobody has ever seen the entire input- output transformation performed by complete circuits in the retina at single-cell resolution,” explains expert E.J. Chichilnisky, PhD. “We think these data will allow us to more deeply understand neuronal computations in the visual system and ultimately may help us construct better retinal implants,” adds the scientist.