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A model of pattern completion based on the CA3 recurrent synapse Jose Guzman, Michael Frotscher and Peter Jonas The neural structure for pattern completion Histologie du Systeme Nerveus de lHomme et des Vertebres, Vols. 1 & 2. A.

  1. A model of pattern completion based on the CA3 recurrent synapse Jose Guzman, Michael Frotscher and Peter Jonas

  2. The neural structure for pattern completion Histologie du Systeme Nerveus de l’Homme et des Vertebres, Vols. 1 & 2. A. Maloine. Paris. 1911. Ramón y Cajal. CA3-CA3 synapses Guzman, Frotscher and Jonas page 2 of 28

  3. Synaptic basics of pattern completion Auto-associative network An autoassociative network can perform pattern completion when it associates the input to the principal cells with their own output (Marr, 1971) 1 Storage 2 Activation 3 Recall Ramón y Cajal, 1911 perforant path 3,600 recurrent 12,000 collaterals mossy fiber 46 0 0 0 0 0 adapted from Amaral et al. , 1990 CA3-CA3 synapses Guzman, Frotscher and Jonas page 3 of 28

  4. Synaptic bases of pattern completion Auto-associative network An autoassociative network can perform pattern completion when it associates the input to the principal cells with their own output (Marr, 1971) 1 Storage 2 Activation 3 Recall Ramón y Cajal, 1911 perforant path 3,600 recurrent 12,000 collaterals mossy fiber 46 0 1 1 0 1 adapted from Amaral et al. , 1990 CA3-CA3 synapses Guzman, Frotscher and Jonas page 4 of 28

  5. Synaptic bases of pattern completion Auto-associative network An autoassociative network can perform pattern completion when it associates the input to the principal cells with their own output (Marr, 1971) 1 Storage 2 Activation 3 Recall Ramón y Cajal, 1911 perforant path 3,600 recurrent 12,000 collaterals mossy fiber 46 0 0 0 0 1 adapted from Amaral et al. , 1990 CA3-CA3 synapses Guzman, Frotscher and Jonas page 5 of 28

  6. Synaptic bases of pattern completion Auto-associative network An autoassociative network can perform pattern completion when it associates the input to the principal cells with their own output (Marr, 1971) 1 Storage 2 Activation 3 Recall Ramón y Cajal, 1911 perforant path 3,600 recurrent 12,000 collaterals mossy fiber 46 0 1 1 0 1 adapted from Amaral et al. , 1990 CA3-CA3 synapses Guzman, Frotscher and Jonas page 6 of 28

  7. Synaptic bases of pattern completion 1 Macro-connectomics CA3–CA3 connectivity? CA3-CA3 synapses Guzman, Frotscher and Jonas page 7 of 28

  8. Synaptic bases of pattern completion 1 Macro-connectomics CA3–CA3 connectivity? 2 Micro-connectomics properties of recurrent synapses CA3-CA3 synapses Guzman, Frotscher and Jonas page 7 of 28

  9. Synaptic bases of pattern completion 1 Macro-connectomics CA3–CA3 connectivity? 2 Micro-connectomics properties of recurrent synapses 3 how are memories stored? (i.e. plasticity rules) CA3-CA3 synapses Guzman, Frotscher and Jonas page 7 of 28

  10. Macro-connectomics what is the connectivity between CA3 cells? CA3-CA3 synapses Guzman, Frotscher and Jonas page 8 of 28

  11. Macro-connectomics: on CA3–CA3 connectivity On CA3 numbers ∼ 40,000 boutons Witter et al., 2007 Li et al., 1994 Ishizuka et al., 1990 ∼ 330,000 CA3 cells Boss et al., 1987 CA3-CA3 synapses Guzman, Frotscher and Jonas page 9 of 28

  12. Macro-connectomics: on CA3–CA3 connectivity On CA3 numbers ∼ 40,000 boutons Witter et al., 2007 Li et al., 1994 Ishizuka et al., 1990 ∼ 330,000 CA3 cells Boss et al., 1987 CA3-CA3 synapses Guzman, Frotscher and Jonas page 10 of 28

  13. Octuple whole-cell recordings a) Simultaneous recordings c) Connectivity matrix to test CA3–CA3 cells b) Recording configurations CA3-CA3 synapses Guzman, Frotscher and Jonas page 11 of 28

  14. Octuple whole-cell recordings a) Simultaneous recordings c) Connectivity matrix to test CA3–CA3 cells b) Recording configurations CA3-CA3 synapses Guzman, Frotscher and Jonas page 12 of 28

  15. Motifs of connectivity a) Simultaneous recordings c) Connectivity motifs are representative b) Motifs of hyperconnectivity CA3-CA3 synapses Guzman, Frotscher and Jonas page 13 of 28

  16. Macro-connectomics what is the connectivity between CA3 cells? CA3 neurons use motifs of hyperconnectivity embedded on a sparse network CA3-CA3 synapses Guzman, Frotscher and Jonas page 14 of 28

  17. Micro-connectomics Properties of the CA3–CA3 synapses CA3-CA3 synapses Guzman, Frotscher and Jonas page 15 of 28

  18. Anatomical identification of synaptic contacts A Biocytine labeling B Identification under light microscopy performed under 60X or 100X/1.4 oil-immersion objectives axon and dendrite belong to functionally connected pairs presence of enlargements at the axon/dendrite. appointments located at a single focal plane. C Nucleated patches Sather et al., 1992 CA3-CA3 synapses Guzman, Frotscher and Jonas page 16 of 28

  20. Micro-connectomics: 1–2 contacts per connection a) Digital reconstruction c) Cable modeling 100 μm b) Putative synaptic contacts d) Conductance estimation CA3-CA3 synapses Guzman, Frotscher and Jonas page 18 of 28

  21. Micro-connectomics: low number of functional sites CA3-CA3 synapses Guzman, Frotscher and Jonas page 19 of 28

  22. Micro-connectomics: low number of functional sites CA3-CA3 synapses Guzman, Frotscher and Jonas page 20 of 28

  23. Micro-connectomics: low number of functional sites CA3-CA3 synapses Guzman, Frotscher and Jonas page 21 of 28

  24. EPSPs are small but add efficiently a) EPSP kinetics c) Spatial summation b) Temporal summation d) Low number of CA3 cells for spiking CA3-CA3 synapses Guzman, Frotscher and Jonas page 22 of 28

  25. Micro-connectomics Properties of the CA3–CA3 synapses CA3 synapses exhibit a low number of sites and summation CA3-CA3 synapses Guzman, Frotscher and Jonas page 23 of 28

  26. Towards a quantitative model for pattern completion CA3-CA3 synapses Guzman, Frotscher and Jonas page 24 of 28

  27. Towards a quantitative model for pattern completion CA3-CA3 synapses Guzman, Frotscher and Jonas page 25 of 28

  28. Towards a quantitative model for pattern completion CA3-CA3 synapses Guzman, Frotscher and Jonas page 26 of 28

  29. Summary 1 Macro-connectomics combination of sparse and dense connectivity CA3-CA3 synapses Guzman, Frotscher and Jonas page 27 of 28

  30. Summary 1 Macro-connectomics combination of sparse and dense connectivity 2 Micro-connectomics small number of synapses, but very prone to summation CA3-CA3 synapses Guzman, Frotscher and Jonas page 27 of 28

  31. Summary 1 Macro-connectomics combination of sparse and dense connectivity 2 Micro-connectomics small number of synapses, but very prone to summation CA3-CA3 synapses Guzman, Frotscher and Jonas page 27 of 28

  32. Acknowledgments 1 Peter Jonas, 2 Alois Schlögl, 3 Jonas lab CA3-CA3 synapses Guzman, Frotscher and Jonas page 28 of 28

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