1. 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 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 CA1 CA3 Entorhinal cortex

8. Background Introduction Connection within the hippocampus Whether Place Cells and Place Recognition Maintained by Direct Entorhinal-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. Material and Methods Remove CA3 Completely Normal  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. Result of retrograde tracing Normal Remove CA3 Completely  Neurons from Entorhinal cortex are labeled  Pyramidal neurons in CA3 are labeled  Failed to label neurons in CA3  Neurons from Entorhinal cortex 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 Sparseness and 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  Blocking input from area CA3 also failed to change the proportion of directionally modulated place cells on the linear track. (P > 0.05)  No group difference in average firing rate : Lesioned rats :1.00Hz Intact rats : 0.91Hz 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. Result of Recognition Annular water maze Sham & CA3  P > 0.25 Sham & HPC  P < 0.005

31. Result of Recall 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 These results 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… 