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Statistical connectivity provides a
sufficient foundation for specific
    functional connectivity in
 neocortical neural microcircuits
Sean L. Hill, Yun Wang, Imad Riachi, Felix Schürmann, and Henry Markram
Contents
•     Short story
•     Long story
•     Meaning
•     Meaning?
•     Conclusion




11/15/2012          Basic biology - Lê Ngọc Minh   2
Long story
1. Functional Synaptic Connectome
2. Statistical Structural Connectome
3. Statistical Structural Connectivity Predicts
   Functional Synaptic Connectivity
4. More about Statistical Structural
   Connectome



11/15/2012         Basic biology - Lê Ngọc Minh   4
1. Functional Synaptic Connectome
• Locations of putative pre- and postsynaptic
  synapses
• Distributions were measured:
      – For presynaptic neurons and postsynaptic neurons
      – In form of histograms
• Connectomes will be compared according to
  these measurements in next steps


11/15/2012             Basic biology - Lê Ngọc Minh    5
Branch order histogram




11/15/2012          Basic biology - Lê Ngọc Minh   6
Path distant histogram




11/15/2012          Basic biology - Lê Ngọc Minh   7
2. Statistical Structural Connectome
• 298 neocortical neurons (pyramidal cells and
  interneurons). The neurons were obtained from
  different experiments and animals, but they were
  always from the same species, region of the
  brain, and age range (rat, somato-sensory area
  S1, and P12 – P16)
• The final dataset included at least seven
  exemplars for each type of neuron morphology
      – [pyramidal cells (PCs), nest basket cells (NBCs), small basket cells
        (SBCs), large basket cells (LBCs), bitufted cells (BTCs), and Martinotti
        cells (MCs)]

11/15/2012                       Basic biology - Lê Ngọc Minh                      8
2. Statistical Structural Connectome
• Randomly select neurons from this pool
  position their somata in a 3D volume
  orresponding to the size of a functional
  neocortical column.
• Identity close appositions between neurons
  using a collision detection algorithm running
  on a supercomputer.
• Compute distribution measurements.

11/15/2012         Basic biology - Lê Ngọc Minh   9
3. Statistical SC Predicts Functional SC
                                                   • The accuracy of the
                                                     predicted synaptic
                                                     locations was tested
                                                     using histogram
                                                     intersection (HI)
                                                   • Significant match of
                                                     innervation patterns is
                                                     tested using the
                                                     Kolmogorov – Smirnov
Overlap according to path distance (left) and        (KS) test (α < 0.05)
overlap according to branch order (right)

11/15/2012                            Basic biology - Lê Ngọc Minh             10
3. Statistical SC Predicts Functional SC




11/15/2012       Basic biology - Lê Ngọc Minh   11
3. Statistical SC Predicts Functional SC




11/15/2012       Basic biology - Lê Ngọc Minh   12
4. More about Statistical Structural
               Connectome
• For the sake of completeness…
• The sensitivity of the structural connectome to
  the precise configuration of the model
  microcircuit (positions, rotations, densities).
• Low variance of statistical connectivity regardless
  of the number of morphology variants.
• The distribution of appositions can be computed
  from volume density representations of
  individual and average dendrites and axons rather
  than the collision detection process.
11/15/2012          Basic biology - Lê Ngọc Minh    13
Meaning
• The relative roles of statistical and
  chemospecific mechanisms in the formation
  of the connectome.
      – Exact positioning within a layer is not critical for
        achieving cell type-specific patterning of synapses.
      – The role of these molecular processes is
        nonspecific and therefore, not aimed at any
        specific pair of neurons.


11/15/2012               Basic biology - Lê Ngọc Minh      14
Meaning
• The processes of arbor alignment and synapse
  formation are separate.
• The diverse morphologies of the different
  classes of pyramidal and interneurons found
  in neocortex serve to ensure a robust and
  invariant set of distributed inputs and outputs
  between specific pre- and postsynaptic
  populations of neurons
• And an easier way to model the brain!

11/15/2012         Basic biology - Lê Ngọc Minh   15
Meaning?
• Small sample size:
      – Number of neurons: 298 << 1011 (100 billion)
      – Number of synaptic connections: 90 << 1014 (100
        trillion)
• Uncertainty: A putative synapse is not
  necessarily a functional synapse although a
  functional synapse is a putative one.
• Measurement: histogram and path distance
  tell nothing about graph topology

11/15/2012             Basic biology - Lê Ngọc Minh       16
Meaning?




             Different topologies having the same histograms

11/15/2012               Basic biology - Lê Ngọc Minh          17
Conclusion
• The idea of statistical connectivity may
  provide an important base for research in
  neuroanatomy.
• The ability of approximating cortical columns
  in computer helps move the Blue Brain Project
  a big step forward.
• However, there are still some issues and
  people should run more experiment to
  confirm its result.

11/15/2012        Basic biology - Lê Ngọc Minh   18
THANK YOU!




11/15/2012    Basic biology - Lê Ngọc Minh   19

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how neurons connect to each others?

  • 1. Statistical connectivity provides a sufficient foundation for specific functional connectivity in neocortical neural microcircuits Sean L. Hill, Yun Wang, Imad Riachi, Felix Schürmann, and Henry Markram
  • 2. Contents • Short story • Long story • Meaning • Meaning? • Conclusion 11/15/2012 Basic biology - Lê Ngọc Minh 2
  • 3.
  • 4. Long story 1. Functional Synaptic Connectome 2. Statistical Structural Connectome 3. Statistical Structural Connectivity Predicts Functional Synaptic Connectivity 4. More about Statistical Structural Connectome 11/15/2012 Basic biology - Lê Ngọc Minh 4
  • 5. 1. Functional Synaptic Connectome • Locations of putative pre- and postsynaptic synapses • Distributions were measured: – For presynaptic neurons and postsynaptic neurons – In form of histograms • Connectomes will be compared according to these measurements in next steps 11/15/2012 Basic biology - Lê Ngọc Minh 5
  • 6. Branch order histogram 11/15/2012 Basic biology - Lê Ngọc Minh 6
  • 7. Path distant histogram 11/15/2012 Basic biology - Lê Ngọc Minh 7
  • 8. 2. Statistical Structural Connectome • 298 neocortical neurons (pyramidal cells and interneurons). The neurons were obtained from different experiments and animals, but they were always from the same species, region of the brain, and age range (rat, somato-sensory area S1, and P12 – P16) • The final dataset included at least seven exemplars for each type of neuron morphology – [pyramidal cells (PCs), nest basket cells (NBCs), small basket cells (SBCs), large basket cells (LBCs), bitufted cells (BTCs), and Martinotti cells (MCs)] 11/15/2012 Basic biology - Lê Ngọc Minh 8
  • 9. 2. Statistical Structural Connectome • Randomly select neurons from this pool position their somata in a 3D volume orresponding to the size of a functional neocortical column. • Identity close appositions between neurons using a collision detection algorithm running on a supercomputer. • Compute distribution measurements. 11/15/2012 Basic biology - Lê Ngọc Minh 9
  • 10. 3. Statistical SC Predicts Functional SC • The accuracy of the predicted synaptic locations was tested using histogram intersection (HI) • Significant match of innervation patterns is tested using the Kolmogorov – Smirnov Overlap according to path distance (left) and (KS) test (α < 0.05) overlap according to branch order (right) 11/15/2012 Basic biology - Lê Ngọc Minh 10
  • 11. 3. Statistical SC Predicts Functional SC 11/15/2012 Basic biology - Lê Ngọc Minh 11
  • 12. 3. Statistical SC Predicts Functional SC 11/15/2012 Basic biology - Lê Ngọc Minh 12
  • 13. 4. More about Statistical Structural Connectome • For the sake of completeness… • The sensitivity of the structural connectome to the precise configuration of the model microcircuit (positions, rotations, densities). • Low variance of statistical connectivity regardless of the number of morphology variants. • The distribution of appositions can be computed from volume density representations of individual and average dendrites and axons rather than the collision detection process. 11/15/2012 Basic biology - Lê Ngọc Minh 13
  • 14. Meaning • The relative roles of statistical and chemospecific mechanisms in the formation of the connectome. – Exact positioning within a layer is not critical for achieving cell type-specific patterning of synapses. – The role of these molecular processes is nonspecific and therefore, not aimed at any specific pair of neurons. 11/15/2012 Basic biology - Lê Ngọc Minh 14
  • 15. Meaning • The processes of arbor alignment and synapse formation are separate. • The diverse morphologies of the different classes of pyramidal and interneurons found in neocortex serve to ensure a robust and invariant set of distributed inputs and outputs between specific pre- and postsynaptic populations of neurons • And an easier way to model the brain! 11/15/2012 Basic biology - Lê Ngọc Minh 15
  • 16. Meaning? • Small sample size: – Number of neurons: 298 << 1011 (100 billion) – Number of synaptic connections: 90 << 1014 (100 trillion) • Uncertainty: A putative synapse is not necessarily a functional synapse although a functional synapse is a putative one. • Measurement: histogram and path distance tell nothing about graph topology 11/15/2012 Basic biology - Lê Ngọc Minh 16
  • 17. Meaning? Different topologies having the same histograms 11/15/2012 Basic biology - Lê Ngọc Minh 17
  • 18. Conclusion • The idea of statistical connectivity may provide an important base for research in neuroanatomy. • The ability of approximating cortical columns in computer helps move the Blue Brain Project a big step forward. • However, there are still some issues and people should run more experiment to confirm its result. 11/15/2012 Basic biology - Lê Ngọc Minh 18
  • 19. THANK YOU! 11/15/2012 Basic biology - Lê Ngọc Minh 19