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how neurons connect to each others?


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how neurons connect to each others?

  1. 1. Statistical connectivity provides asufficient foundation for specific functional connectivity in neocortical neural microcircuitsSean L. Hill, Yun Wang, Imad Riachi, Felix Schürmann, and Henry Markram
  2. 2. Contents• Short story• Long story• Meaning• Meaning?• Conclusion11/15/2012 Basic biology - Lê Ngọc Minh 2
  3. 3. Long story1. Functional Synaptic Connectome2. Statistical Structural Connectome3. Statistical Structural Connectivity Predicts Functional Synaptic Connectivity4. More about Statistical Structural Connectome11/15/2012 Basic biology - Lê Ngọc Minh 4
  4. 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 steps11/15/2012 Basic biology - Lê Ngọc Minh 5
  5. 5. Branch order histogram11/15/2012 Basic biology - Lê Ngọc Minh 6
  6. 6. Path distant histogram11/15/2012 Basic biology - Lê Ngọc Minh 7
  7. 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
  8. 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
  9. 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 – SmirnovOverlap 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
  10. 10. 3. Statistical SC Predicts Functional SC11/15/2012 Basic biology - Lê Ngọc Minh 11
  11. 11. 3. Statistical SC Predicts Functional SC11/15/2012 Basic biology - Lê Ngọc Minh 12
  12. 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
  13. 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
  14. 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
  15. 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 topology11/15/2012 Basic biology - Lê Ngọc Minh 16
  16. 16. Meaning? Different topologies having the same histograms11/15/2012 Basic biology - Lê Ngọc Minh 17
  17. 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
  18. 18. THANK YOU!11/15/2012 Basic biology - Lê Ngọc Minh 19