Place Cells and Place Recognition Maintained by Direct
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
Outline • • • Background Introduction Material and Methods Hypothesis Material and Methods Conclusion III Summary
Background Introduction • Hippocampus : a cognitive (認知) map • Place cell: Hippocampal principal neurons, exhibit location-specific firing. • • Place field CA 1 CA 3 Entorhinal cortex
Background Introduction • Place cells and place fields
Background Introduction • Pyramidal cell: (CA 3)
Background Introduction • Hippocampus : a cognitive (認知) map • Place cell: Hippocampal principal neurons, exhibit location-specific firing. • • Place field CA 1 CA 3 Entorhinal cortex
Background Introduction CA 3 CA 1 Entorhinal cortex
Background Introduction • Connection within the hippocampus Whether Place Cells and Place Recognition Maintained by Direct Entorhinal-Hippocampal Circuitry?
Material and Methods * Subjects and surgery ◆Rat’s Pyramidal cell (in hippocampus) Group 1: Excitotoxic lesions of CA 3 by ibotenic acid. Implant electrodes, record the firing spike.
Material and Methods *Recording 9 11 procedures 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.
Hypothesis • Area CA 3 may not be necessary for establishing and maintaining place fields in area CA 1 • 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.
However, functions of hippocampal neurons may be preformed with relatively small portions of intact hippocampal tissue The place-specific firing in area CA 1, as observed in CA 3 -lesioned rats, could reflect input from remaining CA 3 cells at the septal pole or in more temporal parts of the hippocampus. To isolate the direct entorhinal pathway to CA 1 completely continue the exp…
Material and Methods * Subjects and surgery Rat’s Pyramidal cell (in hippocampus) Group 2: 3 -5 continuous cuts were made between CA 1 and CA 3, to block input from the anterior CA 3 completely. (ibotenic acid is also used. ) ◆
Material and Methods • Remove CA 3 Completely • Normal from Entorhinal cortex
Material and Methods *Retrograde tracing : Inject a fluorescent retrograde tracer that label pyramidal neurons in CA 3 *Recording procedures (like group 1) *Recording procedures (run on a linear track to test the directional modulation)
Result of retrograde tracing • Remove CA 3 Completely • Normal Neurons from Entorhinal cortex are labeled Pyramidal neurons in CA 3 are labeled Neurons from Entorhinal cortex are labeled Failed to label neurons in CA 3
Result of Recording procedures --Disruption of CA 3 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)
Conclusion I • Area CA 3 may not be necessary for establishing and maintaining place fields in area CA 1 • 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.
Discussion • Whether removal of CA 3 input had more subtle effects on place cells in area CA 1? Continue the exp to “Quantitative description of place fields”…. .
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
Result of Sparseness • Distribution of place cells in categories of increasing sparseness Sparseness: 0. 46 for lesioned rats 0. 30 for intact rats
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
Results of Sparseness and Field Size • The result was independent of the type of CA 3 lesion. • These effects were small compared to the differences between the firing fields of pyramidal cells and interneurons.
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
Result of Stability • Stability of place fields in the box across a 1 h interval or a 24 h interval Place fields were Stable across Sessions in both lesioned rats and control rats (P > 0. 05)
Result of Stability • Removal of CA 3 input had no significant effect on how much the peak of the place field moved across a 1 - or 24 - hour interval.
Result of Directional Modulation • Directional modulation No group difference in average firing rate : Lesioned rats : 1. 00 Hz Intact rats : 0. 91 Hz P > 0. 05 Blocking input from area CA 3 also failed to change the proportion of directionally modulated place cells on the linear track. (P > 0. 05)
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 CA 1 Discussion: Whether the reduced circuitry also supported memory? …… continue the exp
Material and Methods * Subjects and surgery Rat’s Pyramidal cell (in hippocampus) ◆ Extensive ibotenate-induced CA 3 lesions ◆ * Recall and recognition tests Annular water maze ◆ Morris milky water maze ◆
Result of Recognition • Annular water maze Sham & CA 3 P > 0. 25 Sham & HPC P < 0. 005
Result of Recall • Morris water maze
Conclusion III • Spatial recognition memory is fully achievable with an isolated entorhinal. CA 1 network. • The isolated entorhinal-CA 1 circuit does not support recall of remote locations or trajectories toward these locations.
Summary • Direct entorhinal-hippocampal connections have significant capacity for transforming weak location-modulated signals. • The isolated entorhinal-CA 1 circuit does not support recall of remote locations or trajectories toward these locations.
Summary • These results suggest that the hippocampus contains two functionally separable memory circuits: The direct entorhinal-CA 1 system is sufficient for recollection-based recognition memory, but recall depends on intact CA 3 CA 1 connectivity.
Comment • Form the result of Morris water maze…
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