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Place Cells and Place Recognition Maintained by Direct Entorhinal-Hippocampal Circuitry

Place Cells and Place Recognition Maintained by Direct Entorhinal-Hippocampal Circuitry. Vegard H. Burn, Mona K. Otnaess, Sturla Molden, Hill-Aina Steffenach, Menno P. Witter, May-Britt Moser, Edvard I. Moser Science VOL 296 , 21 June 2002 Presented by Min-Yu Sun

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Place Cells and Place Recognition Maintained by Direct Entorhinal-Hippocampal Circuitry

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  1. Place Cells and Place RecognitionMaintained by DirectEntorhinal-Hippocampal Circuitry Vegard H. Burn, Mona K. Otnaess, Sturla Molden, Hill-Aina Steffenach, Menno P. Witter, May-Britt Moser, Edvard I. Moser Science VOL 296 , 21 June 2002 Presented by Min-Yu Sun Department of Life Science

  2. Outline • Background Introduction • Material and Methods • Hypothesis • Material and Methods • Conclusion I • Material and Methods • Conclusion II • Material and Methods • Conclusion III • Summary

  3. Background Introduction • Hippocampus :a cognitive (認知) map • Place cell: Hippocampal principal neurons, exhibit location-specific firing. • Place field • CA1 • CA3 • Entorhinal cortex

  4. Background Introduction • Place cells and place fields

  5. Background Introduction • Pyramidal cell: (CA3)

  6. Background Introduction • Hippocampus :a cognitive (認知) map • Place cell: Hippocampal principal neurons, exhibit location-specific firing. • Place field • CA1 • CA3 • Entorhinal cortex

  7. Background Introduction CA3 CA1 Entorhinal cortex

  8. Background Introduction • Connection within the hippocampus Whether Place Cells and Place RecognitionMaintained by DirectEntorhinal-Hippocampal Circuitry?

  9. Material and Methods ＊ Subjects and surgery ◆Rat’s Pyramidal cell (in hippocampus) Group1: Excitotoxic lesions of CA3 by ibotenic acid. Implant electrodes, record the firing spike.

  10. Material and Methods ＊Recording procedures 9 11 3 12 6 11 2 (Hz) Most of the pyramidal neurons had distinct and well-defined place fields that was stable and similar to those normal rats.

  11. Hypothesis • Area CA3 may not be necessary for establishing and maintaining place fields in area CA1 • That spatial information from the neocortex may reach the hippocampus primarily through the alternative route: the direct pathway from layer III of the entorhinal cortex.

  12. However, functions of hippocampal neurons may be preformed with relatively small portions of intact hippocampal tissue The place-specific firing in area CA1, as observed in CA3-lesioned rats, could reflect input from remaining CA3 cells at the septal pole or in more temporal parts of the hippocampus. To isolate the direct entorhinal pathway to CA1 completely continue the exp…

  13. Material and Methods ＊ Subjects and surgery ◆Rat’s Pyramidal cell (in hippocampus) Group2: 3-5 continuous cuts were made between CA1 and CA3, to block input from the anterior CA3 completely. (ibotenic acid is also used.)

  14. Remove CA3 Completely Normal Material and Methods from Entorhinal cortex from Entorhinal cortex

  15. Material and Methods ＊Retrograde tracing : Inject a fluorescent retrograde tracer that label pyramidal neurons in CA3 ＊Recording procedures (like group 1) ＊Recording procedures (run on a linear track to test the directional modulation)

  16. Normal Remove CA3 Completely Result of retrograde tracing Neurons from Entorhinal cortex are labeled Neurons from Entorhinal cortex are labeled Failed to label neurons in CA3 Pyramidal neurons in CA3 are labeled

  17. Result of Recording procedures --Disruption of CA3 input did not attenuate the directional modulation , which is characteristic of place cells in bidirectional environment . (from the same rat) ＊Recording procedures : Color-code firing rate map for a cell that was recorded for five consecutive days in the lesioned rat 8 12 12 17 11 (Hz)

  18. Conclusion I • Area CA3 may not be necessary for establishing and maintaining place fields in area CA1 • That spatial information from the neocortex may reach the hippocampus primarily through the alternative route: the direct pathway from layer III of the entorhinal cortex.

  19. Discussion • Whether removal of CA3 input had more subtle effects on place cells in area CA1? Continue the exp to “Quantitative description of place fields”…..

  20. Material and Methods ＊Quantitative description of place fields ◆Rat’s Pyramidal cell (in hippocampus) ◆ Spike density function ◆Rate map ◆Sparseness ◆ Field size ◆Stability ◆Directional modulation

  21. Result of Sparseness • Distribution of place cells in categories of increasing sparseness Sparseness: 0.46 for lesioned rats 0.30 for intact rats

  22. Result of Field Size • Field Size The size of the place fields was not significantly altered: Lesioned rats- 28.2% surface Intact rats- 18.9% surface The peak rate was reduced: 7.0 Hz for lesioned rats 10.3 Hz for intact rats P < 0.05

  23. Results of Sparsenessand Field Size • The result was independent of the type of CA3 lesion. • These effects were small compared to the differences between the firing fields of pyramidal cells and interneurons.

  24. Material and Methods ＊Quantitative description of place fields ◆Rat’s Pyramidal cell (in hippocampus) ◆ Spike density function ◆Rate map ◆Sparseness ◆ Field size ◆Stability ◆Directional modulation

  25. Result of Stability • Stability of place fields in the box across a 1h interval or a 24h interval Place fields were Stable across Sessions in both lesioned rats and control rats (P > 0.05)

  26. Result of Stability • Removal of CA3 input had no significant effect on how much the peak of the place field moved across a 1- or 24- hour interval.

  27. Result of Directional Modulation • Directional modulation  No group difference in average firing rate : Lesioned rats :1.00Hz Intact rats : 0.91Hz P > 0.05 Blocking input from area CA3 also failed to change the proportion of directionally modulated place cells on the linear track . (P > 0.05)

  28. Conclusion II • The direct pathway from the entorhinal cortex thus seems to be sufficient for establishing and maintaining fundamental properties of place cells in area CA1 Discussion: Whether the reduced circuitry also supported memory? ……continue the exp

  29. Material and Methods ＊ Subjects and surgery ◆Rat’s Pyramidal cell (in hippocampus) ◆ Extensive ibotenate-induced CA3 lesions ＊ Recall and recognition tests ◆ Annular water maze ◆ Morris milky water maze

  30. ResultofRecognition • Annular water maze Sham & CA3 P > 0.25 Sham & HPC P < 0.005

  31. ResultofRecall • Morris water maze

  32. Conclusion III • Spatial recognition memory is fully achievable with an isolated entorhinal-CA1 network. • The isolated entorhinal-CA1 circuit does not support recall of remote locations or trajectories toward these locations.

  33. Summary • Direct entorhinal-hippocampal connections have significant capacity for transforming weak location-modulated signals. • The isolated entorhinal-CA1 circuit does not support recall of remote locations or trajectories toward these locations.

  34. Summary • Theseresults suggest that the hippocampus contains two functionally separable memory circuits:The direct entorhinal-CA1 system is sufficient for recollection-based recognition memory, but recall depends on intact CA3-CA1 connectivity.

  35. Comment • Form the result of Morris water maze… 

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