The impact of pathological high-frequency oscillations on hippocampal network activity in rats with chronic epilepsy
- University of California, San Diego, United States
- University of Bonn Medical Center, Germany
- Ludwig-Maximilians-Universität München, Germany
- Berstein Center for Computational Neuroscience Munich, Germany
Figures
Figure 1 with 2 supplements
High-frequency oscillations in animals with epilepsy compared to control animals.
(A) Each recording session consisted of a sequence of rest epochs (grey blocks) and foraging epochs (white blocks). Rats were placed in either circular (diameter = 1 meter, pictured) or square (0.8 …
Figure 1—figure supplement 1
Detection criteria for high-frequency oscillations (HFO).
(A) LFP recordings from the CA1 cell layer were bandpass filtered and putative HFO events were detected when the RMS surpassed 3.5 standard deviations (step 1) and when the event had at least five …
Figure 1—figure supplement 2
Interictal spikes and noise artifacts are not detected as high frequency oscillations (HFO).
A Example LFP recording from the CA1 cell layer of an epileptic animal. Signals detected as HFOs (see methods section) are indicated by red tick marks on top. An example of a single event (blue box) …
Figure 2 with 1 supplement
Classification of two types of high-frequency oscillations in animals with epilepsy.
A Density plot of high-frequency oscillations (HFOs) recorded from all sessions in control rats (n = 4 rats, n = 4 sessions). All events were characterized by a single cluster of similar frequency …
Figure 2—figure supplement 1
pHFO and ripple-like events are both present in each of the chronically epileptic animals.
A Example ‘ripple’ event recorded from the CA1 cell layer of a control animal. Left: The raw LFP is shown. Middle: To calculate the amplitude of the envelope (the simultaneously occurring voltage …
Figure 3 with 1 supplement
pHFOs occurred during movement-associated theta rhythm.
(A) Cumulative distributions of the running speed at times when a high-frequency oscillation occurred. All data were recorded from behavioral sessions when animals were foraging for food reward and …
Figure 3—figure supplement 1
pHFOs occur at distinct theta phases unique for each animal.
A LFP traces simultaneously recorded from stratum pyramidale (grey) and stratum radiatum (black) from an epileptic rat during a 10-min foraging session. The coherence between the two recorded sites …
Figure 4 with 1 supplement
CA1 principal neurons increase firing rates during control ripple, ripple-like events, and pHFOs.
(A) Coronal section through the area of the hippocampus with tetrode tracks in the CA1 area. The area in the black box is magnified in the inset on the upper left. The tetrode position for the spike …
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Figure 4—source data 1
Neuron activity during control ripple.
Source data correspond to data shown in panel C. For each neuron (neuron # is a unique identifier given to each single unit in the study) several data are shown: (from left to right) the # of SWR ripples (for control), mean rate during baseline (BL), mean rate during detected high-frequency ripple events, and the p-value obtained using a Wilcoxon signed rank test. Neurons are ordered according to p-value, with the smallest p-values at the top. The solid line separates neurons that significantly changed rate during a high-frequency event from those that did not. Neuronal activity during ripple-like oscillations are reported in Figure 4—source data 2 and during pHFO in Figure 4—source data 3.
- https://doi.org/10.7554/eLife.42148.010
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Figure 4—source data 2
Neuron activity during ripple-like oscillations.
Source data correspond to data shown in panel D. For each neuron (neuron # is a unique identifier given to each single unit in the study) several data are shown: (from left to right) the # of ripple-like oscillations (R–L), mean rate during baseline (BL), mean rate during detected high- frequency R-L events, and the p-value obtained using a Wilcoxon signed rank test. Neurons are ordered according to p-value, with the smallest p-values at the top. The solid line separates neurons that significantly changed rate during a high- frequency event from those that did not. Note that all neurons listed in Figure 4—source data 2 are also in Figure 4—source data 3 (but not vice versa), and can be compared by looking at neuron number.
- https://doi.org/10.7554/eLife.42148.011
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Figure 4—source data 3
Neuron activity during pHFO.
Source data correspond to data shown in panel E. For each neuron (neuron # is a unique identifier given to each single unit in the study) several data are shown: (from left to right) the # of pHFOs recorded, mean rate during baseline (BL), mean rate during detected high- frequency events, and the p-value obtained using a Wilcoxon signed rank test. For each table, neurons are ordered according to p-value, with the smallest p-values at the top. The solid line separates neurons that significantly changed rate during a high- frequency event from those that did not. Note that all neurons listed in Figure 4—source data 2 are also in Figure 4—source data 3 (but not vice versa), and can be compared by looking at neuron number.
- https://doi.org/10.7554/eLife.42148.012
Figure 4—figure supplement 1
Spike waveforms are equally stable in control and epileptic animals and cluster quality is high in both groups.
(A) Scatterplots of spike amplitudes on two of the four recording channels (ch1, ch4) from a tetrode different from the one shown in the main Figure 4, but also implanted in an animal with epilepsy. …
Figure 5
Distinct neuronal ensembles are engaged during ripple-like and pHFO events.
(A) Example CA1 pyramidal neuron that is modulated by ripple-like events only. The mean firing rate ±SEM over all ripple-like (blue) and pHFO events (red) is shown, and traces are centered on the …
Figure 6
Place coding deficits in CA1 neurons from animals with epilepsy.
(A) The activity patterns of four control CA1 neurons recorded simultaneously during a 10 min foraging epoch in the open field. Left, for each cell the animal’s path is in grey and the positions …
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Figure 6—source data 1
Spatial coding parameters of place cells in control and epileptic animals.
Neurons are grouped according to whether they are modulated by ripple, ripple-like, or pHFO events. These measures are calculated per foraging periods, such that N reflects the number of neurons multiplied by the number of foraging periods. Values are reported as median; inter-quartile range.
- https://doi.org/10.7554/eLife.42148.016
Figure 7
The spiking of neurons during pHFOs reduce spatial information.
(A) The animal’s path is depicted in grey with the positions where pHFO events occurred overlaid as red dots. The corresponding average rate map is displayed to the right, with a peak rate of 0.16 …
Author response image 1
No relationship between IS /pHFO parameters and magnitude of theta suppression.
(A) Example event recorded simultaneously in the cell layer (stratum pyramidale) and radiatum during movement related theta oscillation. (B) In one foraging session, interictal spikes (IS) recorded …
Author response image 2
Magnitude response of the Equiripple Bandpass Filter.
https://doi.org/10.7554/eLife.42148.021Tables
Key resources table
| Reagent type (species) or resource | Designation | Source or reference | Identifiers |
|---|---|---|---|
| Strain, strain background | Wistar rats; Crl:WI | Charles River Labs | Strain Code: 003; RRID:RGD_13508588 |
| Chemical compound, drug | Kainic acid; kainate | Tocris | Cat # 0222 |
| Chemical compound, drug | Isoflurane | MWI | Cat #: NDC 13985-528-60 |
| Chemical compound, drug | Buprenorphine | MWI | Cat #: 29308 |
| Chemical compound, drug | Chloroplatinic acid for platinum plating | Sigma-Aldrich | Cat #: 206083; CAS 18497-13-7 |
| Chemical compound, drug | Sodium pentobarital | MWI | Cat #: 15199 |
| Chemical compound, drug | Formaldehyde | EMD | Cat #: FX-0415–4; CAS 50-00-0 |
| Chemical compound, drug | Cresyl violet | EMD | Cat #: M-19012; CAS 10510-54-0 |
| Software, algorithm | Matlab v2015b | Mathworks | MATLAB, RRID:SCR_001622 |
| Software, algorithm | MClust | AD Redish | http://redishlab.neuroscience.umn.edu/MClust/MClust.html |
| Software, algorithm | Chronux | Partha Mitra | http://chronux.org/ |
| Other | Hyperdrive | Custom built; Designed by B McNaughton | US Patent: US5928143 A |
| Other | Platinum- Iridium tetrode wire | California fine wire company | Cat #: CFW0011873 |
| Other | Freezing microtome | Leica | Model: SM 2000R |
| Other | Digital Neuralynx recording system | Neuralynx | Model: Digital Lynx SX |
Additional files
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Transparent reporting form
- https://doi.org/10.7554/eLife.42148.018
