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, 11 (10), e0164675
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Optogenetically Blocking Sharp Wave Ripple Events in Sleep Does Not Interfere With the Formation of Stable Spatial Representation in the CA1 Area of the Hippocampus

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Optogenetically Blocking Sharp Wave Ripple Events in Sleep Does Not Interfere With the Formation of Stable Spatial Representation in the CA1 Area of the Hippocampus

Krisztián A Kovács et al. PLoS One.

Erratum in

Abstract

During hippocampal sharp wave/ripple (SWR) events, previously occurring, sensory input-driven neuronal firing patterns are replayed. Such replay is thought to be important for plasticity-related processes and consolidation of memory traces. It has previously been shown that the electrical stimulation-induced disruption of SWR events interferes with learning in rodents in different experimental paradigms. On the other hand, the cognitive map theory posits that the plastic changes of the firing of hippocampal place cells constitute the electrophysiological counterpart of the spatial learning, observable at the behavioral level. Therefore, we tested whether intact SWR events occurring during the sleep/rest session after the first exploration of a novel environment are needed for the stabilization of the CA1 code, which process requires plasticity. We found that the newly-formed representation in the CA1 has the same level of stability with optogenetic SWR blockade as with a control manipulation that delivered the same amount of light into the brain. Therefore our results suggest that at least in the case of passive exploratory behavior, SWR-related plasticity is dispensable for the stability of CA1 ensembles.

Conflict of interest statement

The authors have declared that no competing interests exist.

Figures

Fig 1
Fig 1. Details of the experimental paradigm.
New environments (different shape, and different texture of side-walls) were used on each day, the square box and the circular arena are only shown as examples. Laser pulses were delayed by 1.32 s on control days. Regular, half-intensity laser pulses were used during the final sleep/rest to verify the efficiency of the optogenetic inhibition.
Fig 2
Fig 2
SWR detection and disruption (A, B) In the control condition, ripple oscillations (filtered differential signal in magenta) triggered a 200 ms long detector signal (red square pulses) that was fed back into the recording computer and delayed by 1.32 s. The delayed signals (yellow square pulses) drove the laser and elicited field responses. (C, D) In the SWR-blockade condition, the signal coming from the detector directly drove the laser (yellow square pulses) and readily destroyed the ripples. On all of the panels (A, B, C, D) a tetrode positioned in the CA1 layer with unit activity is shown (green), and another one positioned below (blue). Field responses are obvious on all traces. Lack of inhibition in the interneurons explains the residual unit activity during field responses.
Fig 3
Fig 3
Vanishing high frequency oscillatory activity in the SWR-blockade condition (A) In the control condition, light-time triggered power spectrum shows a prominent peak at 150 Hz and higher frequencies. Here all the data points were shifted forward by 1.32 s, so that the SWR event that actually triggered the light appear at time 0. (B) In the SWR-blockade condition, virtually no oscillatory activity is observable above 150 Hz around the onset of the laser pulse. (C) Normalized power spectrum around off-line detected SWR events. To perform the normalization, spectra were calculated using the multi-taper method around the events, then around time points shifted by 400 ms, and the latter was subtracted from the former. In total, 643 off-line detected SWR events were used for the control condition (continuous line) and 348 for the SWR-blockade condition (dashed line). All of the data presented here (A, B, C) were from the first 20 minutes of the middle sleep and from one example tetrode for each of the conditions. The other tetrodes showed similar activity.
Fig 4
Fig 4. Efficiency of the inhibition.
(A) Efficiency of the optogenetic inhibition of one single CA1 pyramidal cell. Regularly timed 500 ms long half-intensity light pulses were delivered during the final 30 minute long sleep/rest of the day. Spiking activity is displayed as a raster plot centered around the onset of the light pulse (left) and as histogram using 10 ms bins (right). Rebound activity after inhibition can also be observed on the histogram. P-value derived from the Wilcoxon signed rank sum test is shown above the raster. (B) Efficiency of the optogenetic inhibition at population level (22 pyramidal cells are shown from one example recording day). Similarly to other recording days, about 90% of all pyramidal cells were significantly inhibited by the regular 500 ms light pulses.
Fig 5
Fig 5. Stability of one single inhibited CA1 pyramidal cell on a day with SWR blockade.
(A) the place field within the enclosure and the maximum firing rate and the spikes plotted on the trajectory of the animal are shown for the cell before the optogenetic intervention (C) and thereafter. (B) The raster plot and the histogram shows the efficiency of the inhibition. Neither the location of the strongest spiking activity nor the location of the place field in the cross-maze change substantially.
Fig 6
Fig 6. Stability of the firing rate maps.
A selected set of 10 CA1 pyramidal cells, recorded on an SWR-blockade day (A, B) and on a control day (C, D) is shown. For each day, the upper row shows the rate maps before inhibition (A, C), the lower one the rate maps after inhibition (B, D). Note the substantial level of stability on SWR-blockade days.
Fig 7
Fig 7. Sparsity of the cells.
Mean ± SE of the sparsity of the CA1 pyramidal neurons at first exposure (open bars) and second exposure (cross-hatched bars) to the same environment. Sparsities at the first exploration session are significantly different between the control and SWR-block condition (p = 0.004; Oneway ANOVA), as well as for the second exploration session (p = 0.002; Oneway ANOVA). 117 (SWR block) + 116 (CTRL) pyramidal cells were used for this analysis.
Fig 8
Fig 8. Coherence of the cells.
Mean ± SE of the coherence of the CA1 pyramidal neurons at first exposure (open bars) and second exposure (cross-hatched bars) to the same environment. Coherence values at the first exploration session are significantly different between the control and SWR-block condition (p = 0.005; Oneway ANOVA), and the similarly for the second exploration session (p = 0.012; Oneway ANOVA) 117 (SWR block) + 116 (CTRL) pyramidal cells were used for this analysis.
Fig 9
Fig 9. Changes of the average firing rates of the cells.
(A) Firing rate changes (RC) between the first and second exploration of the same environment according to the formula defined in the text, on control days (left bar) and SWR-blockade days (right bar). The difference between the two RC values is not significant (p = 0.092, Oneway ANOVA). (B) The distribution of such changes is shown as a histogram in decimal steps along all possible rate change values. The two distributions are not significantly different (Kolmogorov-Smirnov test; p = 0.179; D = 0.167). 117 (SWR block) + 116 (CTRL) pyramidal cells were used for this analysis.
Fig 10
Fig 10. Stability of the firing rate maps.
(A) Pearson correlation of the firing rate maps between the first and second exploration of the same environment on control days (left bar) and SWR-blockade days (right bar). No significant difference is detected (p = 0.334; Oneway ANOVA). (B) The distribution of such changes is shown as a histogram using bins of 0.1 along all possible correlation values. The two distributions are not significantly different (Kolmogorov-Smirnov test; p = 0.983; D = 0.10).
Fig 11
Fig 11. Stability at the population level.
Cofiring similarity based on the joint firing of cell pairs between the first and the second exploration of the same environment on control days (1649 cell pairs, left bar) and SWR-blockade days (1176 cell pairs, right bar). The difference does not attain the threshold for significance (Z = -0.749; p = 0.454, Fisher’s Z-test).

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Grant support

The research leading to these results has received funding from the People Programme (Marie Curie Actions) of the European Union's Seventh Framework Programme (FP7/2007-2013) under REA grant agreement n° [291734] via the IST FELLOWSHIP awarded to Dr. Krisztián A. Kovács and the European Research Council starting grant (acronym: HIPECMEM Project reference: 281511) awarded to Dr. Jozsef Csicsvari.
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