Development of schemas revealed by prior experience and NMDA receptor knock-out

  1. George Dragoi  Is a corresponding author
  2. Susumu Tonegawa  Is a corresponding author
  1. Massachusetts Institute of Technology, United States
7 figures and 1 table

Figures

Figure 1 with 1 supplement
Experimental design and place cell dynamics across experimental conditions and sessions.

(A) Experimental design displaying sleep/rest - run - sleep/rest sessions across de novo, contiguous, and disjunct experimental conditions. (BD) Color-coded firing rate heat maps of place cells …

https://doi.org/10.7554/eLife.01326.003
Figure 1—figure supplement 1
Stereotypy of the mouse behavior (velocity and distance travelled) during the first four and the last four laps of run during different experimental conditions and sessions and across genotypes.

(A) Average velocity of animal movement. (B) Averages of total distance travelled per lap. Error bars represent SEM. Stars mark significant differences. The difference between the distance travelled …

https://doi.org/10.7554/eLife.01326.004
Prior experience and CA3 NMDARs accelerate tuning and co-variation of place cells in novel environments.

(A) Dynamics of place field length for CT (black color) and KO (red color) during de novo, contiguous, and disjunct conditions. (B) Paired changes in place field length across the first two sessions …

https://doi.org/10.7554/eLife.01326.006
Display of preplay and replay sequences during sleep/rest in naïve and experienced mice in all experimental conditions.

(A and B) Examples of preplay spiking events during the sleep/rest session in the sleep/rest box preceding the first run on the novel track during De novo condition (first three boxes from the …

https://doi.org/10.7554/eLife.01326.007
Significance of preplay and replay events across experimental conditions and genotypes.

(AH) Distribution of absolute values of spiking event-place cell sequence correlations for all events occurring during the pre-Run sleep/rest (open bars, Pre-Run all; solid black bars, …

https://doi.org/10.7554/eLife.01326.008
Figure 5 with 4 supplements
Comparison of hippocampal temporal sequence activity during sleep/rest across multiple novel spatial experiences in individual mice.

(A) Average correlation values for preplay and replay in individual animals and group data. Small letters, (ad), represent different experimental conditions and sessions for A-D. Thin lines …

https://doi.org/10.7554/eLife.01326.009
Figure 5—figure supplement 1
Comparison between preplay of place cell sequences computed from the activity in the early vs late parts of the de novo DnRun1 session in CT and KO mice.

Stars mark significant differences between genotypes.

https://doi.org/10.7554/eLife.01326.010
Figure 5—figure supplement 2
Similar features of preplay and replay during sleep/rest across multiple novel spatial experiences in individual mice.

(A) Average number of cells/per significant event (preplay vs replay). (B) Average duration of preplay and replay events. (C) Proportion of the corresponding track represented by preplay and replay …

https://doi.org/10.7554/eLife.01326.011
Figure 5—figure supplement 3
Histograms depicting co-occurrence of ripple oscillations and preplay/replay events across session, conditions, and genotypes.
https://doi.org/10.7554/eLife.01326.012
Figure 5—figure supplement 4
Immunohistochemistry for NR1 subunit of the NMDA receptor demonstrating the absence of the NMDA receptors specifically in the CA3 area in the KO mice (left) and its preservation in all areas of the hippocampus in the floxed NR1 CT mice.

CA1, CA3, and DG (dentate gyrus) denote subfields of the hippocampal formation.

https://doi.org/10.7554/eLife.01326.013
Behavioral performance of CT and KO mice in a T-maze alternation task.

(A) Performance in the alternation task over the 10 days of training on the first T-maze configuration (T-maze 1; 70% is the performance criterion for learning). Thin lines, learning curves …

https://doi.org/10.7554/eLife.01326.014
Cartoon model of the internal representation of novel experiences based on the organization of neurons in cellular assemblies.

Hexagonal’ panels (panels 1, 4, 6, 8), network of sequentially activated neurons (cell assemblies) during sleep/rest under different experimental conditions: pre-DnRun1 sleep/rest (panel 1), …

https://doi.org/10.7554/eLife.01326.015

Tables

Table 1

The order and duration of the recording sessions

https://doi.org/10.7554/eLife.01326.005
Floxed CT mice
De novo condition, duration (min)Contiguous condition, duration (min)Disjunct condition, duration (min)
Mouse #Pre-DNRun1 sleep/restDnRun1Post-DnRun1 sleep/restDnRun2Post-DnRun2 sleep/restIntervalfRunPre-ContgRun sleep/restFamRun1ContigRunPost-ContgRun sleep/restIntervalFamRun2Pre-DisjRun1 sleep/restDisjRun1Post-DisjRun1 sleep/restDisjRun2
CT12760852134∼24 hr30263691
CT2555469603069603456∼48 hr2996314315
CT3524460316363313487∼48 hr2256194815
CT47837311660∼24 hr2962154281∼48 hr2550152516
CA3 NR1 KO mice
De novo condition, duration (min)Contiguous condition, duration (min)Disjunct condition, duration (min)
Mouse #Pre-DNRun1 sleep/restDnRun1Post-DnRun1 sleep/restDnRun2Post-DnRun2 sleep/restDnRun3Post-DnRun3 sleep/restIntervalfRunPre-ContgRun sleep/restFamRun1ContigRunPost-ContgRun sleep/restIntervalFamRun2Pre-DisjRun1 sleep/restDisjRun1Post-DisjRun1 sleep/restDisjRun2
KO1242536212724117∼24 hr2514103583∼48 hr2253152516
KO255384846602932∼24 hr30305162
KO3594854353030364448∼48 hr4769387021
KO410450321728∼24 hr3623104035∼48 hr3630203520

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