implantable physiological signal wireless telemetry transmitter  (Data Sciences International)

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