By: Matthew A. Wilson & Bruce L. McNaughton GROUP A2: Anna Loza Elyse Rosa Britni Rowe Caroline Olsen Vedran Dzebic Kris Clark

Introduction 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 Kris Clark

Introduction 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 Kris Clark

Introduction  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. Kris Clark

Introduction 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 Kris Clark

Introduction 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 Kris Clark

Design Critique  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. Elyse Rosa

Design Critique  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 Elyse Rosa

Design Critique 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 Elyse Rosa

Procedure Critique 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! Anna Loza

Procedure Critique 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 Anna Loza

Procedure Critique 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” Anna Loza

Procedure Critique 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” Anna Loza

Procedure Critique 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 Anna Loza

Procedure Critique 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…. Anna Loza

Discussion Critique  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” Britni Rowe

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

Pros 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. Vedran Dzebic

Pros  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. Vedran Dzebic

Pros  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 Vedran Dzebic

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 No reports of other screening of rats e.g. vision Caroline Olsen

Further Research  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 Caroline Olsen

Further Research  Averaged readings from many neurons over very wide time bin  Limitations of technology at the time  Frank et al 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 Caroline Olsen

CONSPROSFURTHER RESEARCH Use of extrapolation and estimation Tetrode procedure highly reliable method Wilson et al.(2004) Considered the effects of age Very small sample sizePioneering experiment, which led to many other experiments Gothard et al. (1996) Compared scavenging for reward vs. directional task Lack of constant time constraint Frank et al. (2004) Averaged readings over many neurons over wide time bin Phases appeared to be based around performance No purpose or direction of exploration

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),  Loren M. Frank, Garrett B. Stanley, and Emery N. Brown., The Journal of Neuroscience, September 1, 2004, 24(35):  Griffin, A., Eichenbaum, H., & Hasselmo, M. (2007). The Journal of Neuroscience, 27 (9),  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:  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),