Dynamics of the Hippocampal Ensemble Code for Space

1. Dynamics of the Hippocampal Ensemble Code for Space By: Matthew A. Wilson & Bruce L. McNaughton GROUP A2: Anna Loza Elyse Rosa Britni Rowe Caroline Olsen Vedran Dzebic Kris Clark

2. Introduction Kris Clark Very Brief Overview of Experiment: • Three rats (results used from only 2) • Implanted with electrodes • Trained to forage for chocolate in one half of box (Box A) • Later allowed to venture into other half (Box B) • Compared the readings from electrodes

3. Introduction Kris Clark Longer term exposure to novel environments: • Rats exposed to a novel environment twice, over two days • Rapid changes on first and second days • Even after the representation stabilized, the animals' behavior remained different in the novel places

4. Introduction Kris Clark • This suggested that other brain regions continued to distinguish novel from familiar locations • These results show that the hippocampus can form new spatial representations quickly but that stable hippocampal representations are not sufficient for a place to be treated as familiar.

5. Introduction Kris Clark Context sensitivity of Hippocampus: • It has been indicated that hippocampal neurons are sensitive to subtle changes in task demands, even in an unchanging environment • Learning to differentiate two such contexts was associated with the development of highly context-specific neuronal firing patterns

6. Introduction Kris Clark Overall: • This study implicated the hippocampus in spatial representation, how it is sensitive to novel environments, further elucidating the role of the hippocampus in learning

7. Design Critique Elyse Rosa • Made inferences based on extrapolation • “By extrapolation, 1-cm accuracy over 1s would require about 130 cells.” • Extrapolation is based on trends, which could lead researchers to the correct conclusion • Although these results were likely based on calculations, they should have explained it better in the research paper.

8. Design Critique Elyse Rosa • Number of animals used: • The number of rats used in this study initially  3 • One of the rats didn’t perform like the others so was dismissed • … The remaining conclusions of the experiment were based on 2 rats • More rats would provide slightly more accurate results

9. Design Critique Elyse Rosa Error: 5cm for rat 1 and 2; 2cm for rat 3 EXPERIMENTAL PHASES: • Phase 1: interval in box A before partition removal • Phase 2: the first 10min with the partition between boxes A and B removed • Phase 3: the second 10min interval of this condition • Phase 4: the final time in box A

10. Procedure Critique Anna Loza Rat Exploration in the boxes: • Rat 1: moved freely between the two regions, for 10min phases • Rat 2: explored box B briefly then paused in A for over an hour before resuming exploration • Rat 3: 10 min A (open) 5 min hesitate, 12 min explore, partition close after 20 minutes, 10 min A  6 min phases!

11. Procedure Critique Anna Loza TIMING: • Lack of constant time constraints: • RAT #1: • Phase 1 = 10 minutes • Phase 2 = 10 minutes • Phase 3 = 10 minutes • Phase 4 = 10 minutes • RAT #2: • Phase 1 = 10 minutes • Phase 2 = 6 minutes • Phase 3 = 6 minutes • Phase 4 = 10 minutes

12. Procedure Critique Anna Loza TIMING: • Rat 2 paused for over an hour – but experiment takes 40 minutes…? • Rat 2 data was excluded because of this pause; but “consistent elsewhere”

13. Procedure Critique Anna Loza PHASES: • Phases assigned totally arbitrarily – they let the rat decide the timeframe (and then said they explored for 20 mins) • “The accuracy of reconstruction reflects the consistency of spatial firing over the phase”

14. Procedure Critique Anna Loza DIRECTION: • Place cells are directional when an animal takes limited paths, but non-directional when wondering randomly on an open field (McNaughton,Barnes,and O’Keefe 1983) It may help if rats had a “purpose” in their exploration for directional recordings to be made

15. Procedure Critique Anna Loza TEST: • The test seems to have been performed only once? • Need an average of rat’s behaviour: • What if they are afraid of novelty? • Have they ever done this before? • Ideally, they should have been trained, and then presented with another novel environment to be tested on….

16. Discussion Critique Britni Rowe • Strong statements based on 2 rats: “ Incorporation of new spatial information has little effect on previously stored information, at least within the limits of this experiment”

17. Discussion Critique Britni Rowe • Strong statements based on 2 rats (continued): “…suggests that the synaptic modification mechanisms that are presumably involved are rapid”

18. Pros Vedran Dzebic TETRODE PROCEDURE: • Multiple unit spike trains from multi-unit recordings is not always accurate • Tetrode developed by Wilson and McNaughton eliminates this problem • Has the ability to identify and measure many individual neurons • Can measure the activation during many different states and activities.

19. Pros Vedran Dzebic • Considering the small sample size, and limitations, the results and the extrapolation are in line with what you expect • Previous attempts with single unit recordings failed to show different firing after experience in environment.

20. Pros Vedran Dzebic • The concept of looking for activation in specific cells, as rats move through environment provides a good basis for measuring cell activation, but would be better if goal is implemented. • Demonstrates the important point of ensemble neural activity

21. Caroline Olsen Further Research • EFFECTS OF AGE: • Age of rats not published • Changes in hippocampal connectivity and plasticity impairs spatial learning in older rats • Aged rats maintain familiar representations in novel environments • Delayed in anchoring new representations to external landmarks • New spatial representations are multi-stable across repetitive exposures to the previously novel environment -Wilson et al. 2004 • No reports of other screening of rats e.g. vision

22. Further Research Caroline Olsen • Compare scavenging for reward vs. directional task • Place cells are non-directional when wandering randomly • Directional when taking limited paths • Some hippocampal CA1 cells encode location with respect to reference frames associated with the task Gothard et al. 1996

23. Further Research Caroline Olsen • Averaged readings from many neurons over very wide time bin • Limitations of technology at the time • Frank et al. 2004 measured on millisecond time scale and results were consistent • Also found decrease in inhibitory neuron activity in first exposure to novel environment • Also reassess stability of representations of formerly novel environment on subsequent exposure Frank et al. 2004

25. References • Frank, L. M., Stanley, G. B., & Brown, E. N. (2004). Hippocampal plasticity across multiple days of exposure to novel environments. The Journal of Neuroscience, 24(35), 7681-7689. • Loren M. Frank, Garrett B. Stanley, and Emery N. Brown., The Journal of Neuroscience, September 1, 2004, 24(35):7681-7689 • Griffin, A., Eichenbaum, H., & Hasselmo, M. (2007). The Journal of Neuroscience, 27 (9), 2416-2423. • Redish. A.D. (1999).Beyond the Cognitive Map.MIT Press • Wilson, M.A., & McNaughton, B. (1993). Dynamics of the hippocampal ensemble code for space. Science 261: 1055-1058 • Wilson, I. A., McMahan, R. W., Gallagher, M., Eichenbaum, H., & Tanila, H. (2004). Cognitive aging and the hippocampus: How old rats represent new environments. The Journal of Neuroscience, 24(15), 3870-3878.