Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2014:2014:675128.
doi: 10.1155/2014/675128. Epub 2014 Mar 20.

Involvement of thalamus in initiation of epileptic seizures induced by pilocarpine in mice

Yong-Hua Li  1 , Jia-Jia Li  2 , Qin-Chi Lu  2 , Hai-Qing Gong  1 , Pei-Ji Liang  1 , Pu-Ming Zhang  1
Affiliations

Involvement of thalamus in initiation of epileptic seizures induced by pilocarpine in mice

Yong-Hua Li et al. Neural Plast. 2014.

Abstract

Studies have suggested that thalamus is involved in temporal lobe epilepsy, but the role of thalamus is still unclear. We obtained local filed potentials (LFPs) and single-unit activities from CA1 of hippocampus and parafascicular nucleus of thalamus during the development of epileptic seizures induced by pilocarpine in mice. Two measures, redundancy and directionality index, were used to analyze the electrophysiological characters of neuronal activities and the information flow between thalamus and hippocampus. We found that LFPs became more regular during the seizure in both hippocampus and thalamus, and in some cases LFPs showed a transient disorder at seizure onset. The variation tendency of the peak values of cross-correlation function between neurons matched the variation tendency of the redundancy of LFPs. The information tended to flow from thalamus to hippocampus during seizure initiation period no matter what the information flow direction was before the seizure. In some cases the information flow was symmetrically bidirectional, but none was found in which the information flowed from hippocampus to thalamus during the seizure initiation period. In addition, inactivation of thalamus by tetrodotoxin (TTX) resulted in a suppression of seizures. These results suggest that thalamus may play an important role in the initiation of epileptic seizures.

PubMed Disclaimer

Figures

Figure 1
Figure 1
Multichannel microelectrode recordings. Two bundles of electrodes were inserted into the CA1 region of the left hippocampus and PF region of the left thalamus, respectively. Each bundle consists of two tetrodes and each tetrode is formed of four insulated nickel-chrome alloy electrodes (diameter of 13 μm, impedance of 0.5–1.0 MΩ). For each electrode, we extracted single-unit activities and LFPs. Single-unit activities were obtained by filtering the recording at 300–6000 Hz and sorting the filtered data using OfflineSorter software (Plexon Co, USA). To obtain the LFPs, we filtered the data at 0.5–100 Hz. (a) Multichannel microelectrode. The enlarged view shows one bundle of electrodes consisted of two tetrodes and the cross-section through a tetrode. (b) LFPs from a tetrode in the normal hippocampus. (c) Multiunit activity (MUA) of the same tetrode. (d) Example of single-unit activity. The upper trace is the spike train sorted from the MUA in (c). The spikes were from four neurons denoted by four colors. The left bottom traces show the superimposed single waveforms of spikes of four neurons. The right bottom figure shows the four clusters in the feature space, which were projected by the spikes of the four neurons, by using the principal component analysis (PCA) method. H, hippocampus; T, thalamus; T1&T2, Tetrode 1 and Tetrode 2 in a bundle. For example, H-T1-2 means the second channel of Tetrode 1 in hippocampus.
Figure 2
Figure 2
LFPs during the first seizure of an example mouse. (a) Single seizure recorded by four tetrodes. All data were filtered at 0.5–100 Hz. The seizure onset time is marked by an arrow. (b) Power spectral of LFP from Channel H-T2-4. (c) The details of the recordings shown in the shadow in (a). (C1) shows the tonic phase of epileptic seizure and (C2) shows the clonic phase of epileptic seizure. H, hippocampus; T, thalamus; T1&T2, Tetrode 1 and Tetrode 2 in a bundle.
Figure 3
Figure 3
Peri-ictal changes of electrical brain activities as assessed by redundancy (R) of LFP and cross-correlation function (CCF) of single-unit activities. (a) LFPs of two sample seizures from Mouse #2 and Mouse #6. Seizure onset is marked by red line. (b) Peri-ictal changes of R of LFPs during the seizures shown in (a). (c) Dynamic changing of peak values of CCF of two neuronal spike trains sorted from tetrode H-T2 in Mouse #2 and tetrode T-T1 in Mouse #6. (d) Raster of the spikes from two neurons sorted from the two tetrodes above (shadows in (c)) and CCF in the periods of 5 s marked by (A), (B), and (C) in (c). H, hippocampus; T, thalamus; T1&T2, Tetrode 1 and Tetrode 2 in a bundle.
Figure 4
Figure 4
Statistics analysis result of signal redundancy for all 9 mice. (a) Time periods' definition. Control period contains 120 s before the pilocarpine injection. Pre-seizure (PreSz) time period is before the seizure onset with 120-s long. Post-seizure (PostSz) time period is immediately after seizure termination with 30 s long. Time period between seizure onset and termination is denoted as “Sz.” (b) Statistical analysis results of redundancy (R). Error bar means standard deviation. Stars (∗) indicate statistically significant differences between the distributions for control period and the following three time periods (pair-wised t-tests, significance level P < 0.05). Hipp, hippocampus; Tha, thalamus; PILO, pilocarpine.
Figure 5
Figure 5
One example of peri-ictal coupling dynamics between hippocampus and thalamus. (a) Mean values of LFPs recorded from four channels of each tetrode. (b) The directionality index (D XY) between hippocampus and thalamus. We calculated D XY between each tetrode's recording from hippocampus and thalamus of the example mouse, getting four combinations. (c) The averaged directionality index (D XY). The red line indicates the seizure onset time. H, hippocampus; T, thalamus; T1&T2, Tetrode 1 and Tetrode 2 in a bundle.
Figure 6
Figure 6
Peri-ictal coupling dynamics between hippocampus and thalamus. (a) Time course of directionality index (D XY) between hippocampus and thalamus during the epileptic seizures in 9 mice. The upper two traces show the averaged LFPs from hippocampus and thalamus. The lower trace shows the averaged D XY. The red line indicates the seizure onset time. (b) Time periods' definition. We divided the Sz period into three parts. The first part is the initiation period of seizure (IS), containing one-fifth of the time course of seizure from the seizure onset. The third part is the end of seizure (ES), containing one-fifth of the time course of seizure immediately before the termination of seizure. The second part is the middle part of the seizure (MS) between the first and the third part. (c) Percentages of coupling direction “hippocampus → thalamus” and “thalamus → hippocampus” during the initiation period of seizure (IS). The black solid line marks the threshold of 50%. Hipp, hippocampus; Tha, thalamus.
Figure 7
Figure 7
Seizures affected by the TTX injection in thalamus. (a) LFPs from hippocampus and thalamus and the averaged directionality index (D XY) between the two brain areas before and after the injection of TTX into thalamus. (b) The power spectral density of the LFPs in hippocampus (shadowed areas in (a)). (c) 60-second samples from each trace in (a) (the shadowed areas). (d) LFPs from hippocampus and thalamus and averaged directionality index (D XY) between the two brain areas before and after the injection of normal saline into thalamus in a control mouse. (e) The power spectral density of the LFPs in hippocampus (shadowed areas in (d)). (f) 60-second samples from each trace in (d) (the shadowed areas). Hipp, hippocampus; Tha, thalamus.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Kuruba R, Hattiangady B, Shetty AK. Hippocampal neurogenesis and neural stem cells in temporal lobe epilepsy. Epilepsy and Behavior. 2009;14(1):65–73. - PMC - PubMed
    1. Pilli J, Abbasi S, Richardson M, Kumar SS. Diversity and excitability of deep-layer entorhinal cortical neurons in a model of temporal lobe epilepsy. Journal of Neurophysiology. 2012;108(6):1724–1738. - PubMed
    1. Aroniadou-Anderjaska V, Fritsch B, Qashu F, Braga MFM. Pathology and pathophysiology of the amygdala in epileptogenesis and epilepsy. Epilepsy Research. 2008;78(2-3):102–116. - PMC - PubMed
    1. Williamson PD, French JA, Thadani VM, et al. Characteristics of medial temporal lobe epilepsy: II. Interictal and ictal scalp electroencephalography, neuropsychological testing, neuroimaging, surgical results, and pathology. Annals of Neurology. 1993;34(6):781–787. - PubMed
    1. King D, Spencer SS. Invasive electroencephalography in mesial temporal lobe epilepsy. Journal of Clinical Neurophysiology. 1995;12(1):32–45. - PubMed

Publication types