DOI: 10.5061/dryad.66t1g1kds
title: Data from: Restoring failed inhibition in the substantia nigra pars reticulata suppresses absence seizures in rats

description: 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.
description: # Data from: Restoring failed inhibition in the substantia nigra pars
 reticulata suppresses absence seizures in rats Dataset DOI:
 [10.5061/dryad.66t1g1kds](https://doi.org/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](https://github.com/kostasrotas/EDFViewer-Desktop) * A stand alone EDF Viewer available for Windows, MacOS, and Ubuntu * [https://github.com/holgern/pyedflib](https://github.com/holgern/pyedflib) * A python-based EDF Viewer * [https://www.mathworks.com/help/signal/ref/edfread.html](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](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](https://www.neuroexplorer.com/docs/guides/readwritefiles.html) including Matlab, Python, and C code to read and write Nex5 files.