Journal: Cell

Article Title: The gut microbiota mediates the anti-seizure effects of the ketogenic diet

doi: 10.1016/j.cell.2018.04.027

Figure Lengend Snippet: KEY RESOURCES TABLE

Article Snippet: Detailed methods are provided and include the following: REAGENT or RESOURCE SOURCE IDENTIFIER Bacterial and Virus Strains Akkermansia muciniphila ATCC ATCC BAA845 Parabacteroides merdae ATCC ATCC 43184 Parabacteroides distasonis ATCC ATCC 8503 Bifidobacterium longum ATCC ATCC 15707 Chemicals, Peptides, and Recombinant Proteins GGsTop, 3-[[(3-amino-3-carboxypropyl) methoxyphosphinyl]oxy]benzeneacetic acid Tocris Bioscience 4452; CAS: 926281-37-0 Mucin from porcine stomach, type III Sigma-Aldrich M1778; CAS: 84082-64-4 L-gamma-glutamyl-3-carboxy-4-nitroanilide Gold Bio G-380-1; CAS: 63699-78-5 4 kDa FITC-dextran Sigma-Aldrich 46944; CAS: 60842-46-8 Critical Commercial Assays Glucose Colorimetric Assay Kit Cayman Chemical Cat# 10009582 Beta-hydroxybutyrate Colorimetric Assay Kit Cayman Chemical Cat# 700190 MoBio PowerSoil Kit Mo Bio Cat# 12888-100 Deposited Data 16S rDNA sequences This paper https://qiita.ucsd.edu , 11566 Experimental Models: Organisms/Strains Mouse: Swiss Webster, germ-free Taconic Taconic: SW GF Mouse: Swiss Webster, specific pathogen-free Taconic Taconic: SW MPF Mouse: Kcna1−/−: C3HeB.129S7-Kcna1 tm1|em /J Dr. Bruce Tempel JAX: 003532 Oligonucleotides MUC1437: 6FAM-CCTTGCGGTTGGCTTA Derrien, et al., 2008 Sigma Aldrich: custom oligo BAC303: Texas Red-CCAATGTGGGGGACCTT Manz, et al., 1996 Sigma Aldrich: custom oligo Software and Algorithms Ethovision XT 11 Noldus Cat # EX11-MAMBP-E QIIME1.8.0 Caporaso et al., 2010 http://qiime.org/ Greengenes Lawrence Berkeley National Labs http://greengenes.lbl.gov/cgi-bin/nphindex.cgi PICRUSt Langille et al., 2013 http://picrust.github.io/picrust/ Ponemah V5.1 Data Sciences International https://www.datasci.com/products/software/ponemah Neuroscore Data Sciences International https://www.datasci.com/products/software/neuroscore TraceFinder 3.3 ThermoFisher Scientific OPTON-30491 ImageJ National Institutes of Health https://imagej.nih.gov/ij/ Other Ketogenic Diet Mouse Chow Envigo TD.07797.PWD Control Diet Mouse Chow Envigo TD.150300 Standard Diet Mouse Chow LabDiet # 5010 ECT Unit Ugo Basile Model # 57800 EEG transmitters Data Sciences International PhysioTel ETA-F10 Open in a separate window KEY RESOURCES TABLE CONTACT FOR REAGENT AND RESOURCE SHARING Further information and requests for resources and reagents should be directed to and will be fulfilled by the Lead Contact, Elaine Hsiao ( ude.alcu@oaishe ) EXPERIMENTAL MODELS AND SUBJECT DETAILS Mice 3–4 week old SPF wildtype Swiss Webster mice (Taconic Farms), GF wildtype Swiss Webster mice (Taconic Farms) and SPF C3HeB/FeJ KCNA1 KO mice (Jackson Laboratories) were bred in UCLA’s Center for Health Sciences Barrier Facility.

Techniques: Virus, Recombinant, Colorimetric Assay, Software, Control

Journal: bioRxiv

Article Title: Interneuron theta phase locking controls seizure susceptibility

doi: 10.1101/2025.09.10.675457

Figure Lengend Snippet: A) PV-Cre and SOM-Cre mice received pilocarpine status epilepticus (SE) or saline (Control), and two weeks later were injected with Cre-dependent ChR2 virus into dorsal hippocampus, and a headbar and wireless EEG transmitter were implanted. Mice were trained to navigate a virtual linear environment and an acute silicon probe recording was performed with channels spanning the dorsal hippocampus. Putative PV+ or SOM+ cells were identified with blue light delivery. Representative waveforms, rasters, and firing rate histograms from a putative opto-tagged PV+ cell (yellow) and SOM+ cell (green). Mean waveforms in yellow and green are shown overlaid against 100 randomly selected individual spike traces from the same cell cluster. Waveform scale: 250µs by 50µV (PV) or 20µV (SOM). B) Opto-tagged PV+ cells in the DG of saline-treated control mice showed tightly clustered mean preferred firing phases (mu) near the theta trough. Opto-tagged DG SOM+ cells from saline-treated control SOM-Cre mice also had phase preferences around the theta trough (PV+ vs SOM+ Kuiper test p≤0.05; Watson-Williams test p=0.618), but were significantly more dispersed (PV+ vs SOM+ circular k-test p<0.0001). SOM+: n=9 cells from N=3 mice, PV+: n=28 cells from N=6 mice. C) Both DG PV+ and SOM+ cells’ firing rates fluctuated across the theta cycle (20° bins), with firing rates highest in both cell populations around the theta trough, however PV+ cells showed a trend towards greater firing rate modulation based on theta phase. (Two-way repeated measures ANOVA comparing firing based on: cell-type (SOM+ vs PV+) p=0.368, or theta bin p<0.005, or the interaction between cell-type and theta bin p=0.051). D) The magnitude of theta phase locking (r-value) was similar in opto-tagged DG PV+ and SOM+ cells in healthy mice (unpaired t-test p=0.685). E) Pilocarpine-induced SE produced chronic spontaneous seizures in PV-Cre and SOM-Cre mice (combined), while saline-treated controls did not seize (Welch’s t-test p=0.011, N=10 Control, N=11 Pilo mice). F) Inhibitory neurons in the DG of epileptic mice showed altered distribution of mu values (i.e., mean preferred firing phases) relative to controls (Kuiper test p≤0.001; Watson-Williams test p=0.637; circular k-test p<0.0001; Pilo n=72 cells, N=9 mice; Control n=137 cells, N=14 mice). G) DG inhibitory neurons in epileptic mice had reduced magnitude of theta phase locking (r-values) compared to controls (unpaired t-test p=0.003; Pilo n=95 cells, N=10 mice; Control n=147 cells; N=14 mice). H) Opto-tagged PV+ cells in the DG of epileptic mice had significantly altered distributions of preferred firing phases relative to PV+ cells in controls (Kuiper test p≤0.001, circular k-test p<0.0001) but no shift in the population’s mean firing phase (Watson-Williams test p=0.649; Pilo: n=15 cells, N=3 mice, Control n=27 cells, N=6 mice). Note that the opto-tagged PV+ interneuron data from healthy mice are also shown in panels B-D, and only significantly phase-locked cells are included here. I) Opto-tagged PV+ interneurons in the DG showed altered firing rates across the theta cycle (two-way repeated measures ANOVA comparing firing rates based on experimental group (Control vs Pilo p=0.533, theta bin p<0.0001, or the interaction of group and theta bin p=0.021, Pilo n=17 cells, N=3 mice; Control n=28 cells, N=6 mice). J) Opto-tagged PV+ cells in the DG showed equivalent strength of theta phase modulation in control and epileptic mice (unpaired t-test, p=0.530; Pilo n=17 cells, N=3 mice; Control n=28 cells, N=6 mice). K-M) No opto-tagged SOM+ cells were identified in the DG of epileptic SOM-Cre mice (N=6 Pilo mice), and therefore their theta phase locking profiles could not be characterized. Note that the opto-tagged SOM+ cells from controls are also shown in panels B-D. n=9 cells from N=3 control mice. Note that the theta cycle is double plotted for visualization purposes in panels B, C, F, H, I, K, L. * indicates p<0.05. ** indicates p<0.01. *** indicates p<0.001.

Article Snippet: To chronically monitor seizures, a wireless EEG transmitter (PhysioTel ETA-F10; Data Sciences International) was implanted under the skin, posterior to the left ribcage, but anterior to the left haunch.

Techniques: Saline, Control, Injection, Virus, Produced

Journal: bioRxiv

Article Title: Interneuron theta phase locking controls seizure susceptibility

doi: 10.1101/2025.09.10.675457

Figure Lengend Snippet: A) Schematic of hypotheses. Top: in epileptic mice, Trough Stim (trough excitation with peak inhibition) re-aligns DG inhibition to the trough of CA1 theta, when input excitation is strongest. Bottom: in control mice, Peak Stim (peak excitation with trough inhibition) mis-aligns DG inhibition, so inhibition is weakest when input excitation is strongest, creating seizure vulnerability points at the theta trough. B) Experimental timeline schematic. PV-Cre and SOM-Cre mice received pilocarpine status epilepticus (SE) or saline (Control), and four weeks later were injected with Cre-dependent somBiPOLES virus into dorsal DG, and a headbar and wireless EEG transmitter were implanted. Three weeks later, an acute silicon probe recording was performed with channels spanning the dorsal hippocampus. Following a baseline period, mice were injected intraperitoneally with kainic acid and either peak-targeted or trough-targeted stimulation was applied until seizure onset. C) Latency to seizure in epileptic PV-Cre mice (left, male mice) was significantly increased compared to opsin-when PV+ cells were re-aligned to the trough of CA1 theta (Kruskal-Wallis ANOVA p=0.040; with Dunn’s post hoc tests comparing Trough vs Opsin-, p=0.041; and Peak vs Opsin-, p>0.999). Latency to seizure in PV-Cre control mice (right, male and female mice) was significantly reduced compared to opsin-when PV+ cells were mis-aligned to the peak of CA1 theta (one-way ANOVA p=0.039 with Dunnett’s multiple comparison post hoc tests comparing Trough vs Opsin-, p>0.999; and Peak vs Opsin-, p=0.046). D) No significant effects of manipulating SOM+ cell phase locking on latency to seizure in epileptic (left, one-way ANOVA p=0.741) or control (right, one-way ANOVA p=0.273) mice.

Article Snippet: To chronically monitor seizures, a wireless EEG transmitter (PhysioTel ETA-F10; Data Sciences International) was implanted under the skin, posterior to the left ribcage, but anterior to the left haunch.

Techniques: Inhibition, Control, Saline, Injection, Virus, Comparison