Data from: Restoring failed inhibition in the substantia nigra pars reticulata suppresses absence seizures in rats

Published Dec 08, 2025 on Dryad. https://doi.org/10.5061/dryad.66t1g1kds

Data files

Dec 08, 2025 version files 6.54 GB

Abstract

Objective

For over four decades, the substantia nigra pars reticulata (SNr) has been recognized as a critical structure in the modulation of seizure activity. Pharmacological and optogenetic inhibition of the SNr produce robust seizure suppression in a range of seizure models. These findings have given rise to a longstanding, yet unresolved question: do seizures involve a failure of inhibition within the SNr?

Methods

We recorded single-unit activity in the SNr during spike-and-wave discharges (SWDs) in male and female WAG/Rij rats, a model of genetic absence epilepsy. We monitored extracellular GABA levels using intensity-based GABA sensing fluorescence reporter (iGABASnFR). To emphasize the multi-modal efficacy of SNr inhibition on seizure suppression, we optogenetically inhibited the SNr.

Results

50% of recorded neurons exhibited a marked increase in firing at SWD onset, with activity returning to baseline at SWD termination. Extracellular GABA levels revealed a decrease in fluorescence during SWDs, consistent with reduced GABAergic transmission. Optogenetic inhibition of SNr neurons using continuous (open-loop) inhibition, but not closed-loop (responsive) inhibition, significantly reduced SWD incidence.

Significance

These data suggest that a loss of GABAergic input to the SNr is associated with increased neuronal activity. Optogenetically restoring inhibition effectively reduced seizure burden. Together, these findings address a long-standing gap in the literature and provide compelling evidence that impaired inhibition within the SNr contributes to seizure expression.

Dataset DOI: 10.5061/dryad.66t1g1kds

Description of the data and file structure

File: SNr.Optogenetics.zip

Description: A zip archive with folders containing European Data Format (EDF) electroencephalography (EEG) files for each test session for each subject, organized by virus. Files show a full baseline, 100Hz Open Loop or 100Hz Closed Loop session for each animal with electrographic activity recorded from cortical EEG and stimulator feedback (when relevant)showing the timing of light delivery and closed loop macro seizure detection (when relevant).

Data are organized into two separate folders based on virus used.

“GFP.Control” are recordings from animals injected with a control AAV virus expressing green fluorescent protein but no opsin.
“ArchT” are recordings from animals injected with AAV coding for archaerohodopsin (ArchT) to inhibit the substantia nigra pars reticulata.
Subfolders within each of these folders contains a baseline, open loop, and closed loop session for each subject.
Each file is named following the convention Animal Identifier.Virus.Session
In cases in which multiple baseline files are present, [indicated by a number in parenthesis following baseline], these represent the full session, in sequence, with each file indicating a new data block due to a glitch in recording.

File: Quantification.xlsx

Description: An Excel file showing the values obtained following the quantification of seizures for each animal in the study. The file has two sheets:

Open Loop 100Hz: Quantification of spike-and-wave discharges during open loop optogenetic inhibition of the SNr (and paired baseline trial) for all animals included in the study. Animals receiving ArchT are on the top, and animals receiving GFP are on bottom.

Closed Loop 100Hz: Quantification of spike-and-wave discharges during closed loop optogenetic inhibition of the SNr matched to within-session control (not stimulated) spike-and-wave discharges for all animals included in the study. Animals receiving ArchT are on the top and animals receiving GFP are on bottom.

File: GABASnFr_SNpr.zip

Description: A zip archive containing folders for each animal used for fiber photometry recording. Animal sex is indicated by the first character (F = female; M=male). Each folder contains three comma separated value files (.csv), indicated by the suffixes EEG, Photometry, and Timestamp. The EEG file contains timestamps and EEG values (in microvolts). The Timestamp file contains frame number and timestamps for the photometry data which can be used to align the photometry data to the EEG data. Photometry file contains columns for FrameCount (frame number), SystemTime, LedState (6 = frames where the 470nm LED is active; 1 = frames where the 415 nm (control wavelength) LED is active), and the last four columns contain fluorescence signal for the green and red channels in the left and right hemisphere. Red channels were not used for these studies and can be ignored. The data from the left hemisphere of animal F110R and the right hemisphere of animal M118L were not included in analysis as no signal and/or high levels of noise were present.

File: Single_Unit_Recordings.zip

Description: A zip archive containing .nex5 (NeuroExplorer) files for each recording session that contributed to the single unit analyses in the parent study. Each file is designated by the animal ID and contains the timestamps for spikes for each unit included and the EEG signal for the session derived from the common average reference of the electrodes referenced to a cortical ground screw.

Code/software

Several options are available for viewing EDF files:

https://github.com/kostasrotas/EDFViewer-Desktop
- A stand alone EDF Viewer available for Windows, MacOS, and Ubuntu
https://github.com/holgern/pyedflib
- A python-based EDF Viewer
https://www.mathworks.com/help/signal/ref/edfread.html
- Matlab natively supports EDF viewing through the edfread command

Analysis code for photometry and single unit data:

https://github.com/forcelli-lab/Palmer-et-al_Epilepsia

Documentation on the .nex5 file format can be found at:

https://www.neuroexplorer.com/docs/guides/readwritefiles.html

including Matlab, Python, and C code to read and write Nex5 files.