Absence seizures result from 3-5 Hz generalized thalamocortical oscillations that depend on highly regulated inhibitory neurotransmission in the thalamus. Efficient reuptake of the inhibitory neurotransmitter GABA is essential, and reuptake failure worsens seizures. Here, we show that blocking GABA transporters (GATs) in acute brain slices containing key parts of the thalamocortical seizure network modulates epileptiform activity. As expected, we found that blocking either GAT1 or GAT3 prolonged oscillations. However, blocking both GATs unexpectedly suppressed oscillations. Integrating experimental observations into single-neuron and network-level computational models shows how a non-linear dependence of T-type calcium channel opening on GABA_B receptor activity regulates network oscillations. Receptor activity that is either too brief or too protracted fails to sufficiently open T-type channels necessary for sustaining oscillations. Only within a narrow range does prolonging GABA_B receptor activity promote channel opening and intensify oscillations. These results have implications for therapeutics that modulate GABA transporters.

See the first two subsections of the Methods section in the associated paper.

Oscillation recordings in acute thalamic slices and dynamic clamp recordings in thalamocortical neurons are included. Analysis and simulation results can be reproduced from code available here: https://github.com/luadam4c/m3ha_published.

Oscillations data:

The data are separated into 4 directories, corresponding to the following perfusion conditions:
(1) control: bicuculline-ACSF
(2) no711: bicuculline-ACSF plus 4 μM NO-711 to block GAT1 transport
(3) snap5114: bicuculline-ACSF plus 100 μM SNAP-5114 to block GAT3 transport 
(4) dual: bicuculline-ACSF plus a combination of 4 μM NO-711 and 100 μM SNAP-5114 to simultaneously block both GAT1 and GAT3

Raw multiunit data (filtered between 100-3000 Hz) are packaged into MATLAB .mat files, one for each slice. Metadata and analyzed results for all 60 second sweeps are available as comma-separated value (.csv) files, one for each slice. Master scripts used for analysis were m3ha_oscillations_analyze.m, parse_all_multiunit.m, parse_multiunit.m, plot_measures.m.

Dynamic clamp data:

Raw dynamic clamp recording data are available as Axon Binary Format (.abf) files. Each trace includes a short current pulse response (current pulse applied at approximately 100-110 ms) and an IPSC response (IPSC applied at 1000 ms). To extract and reorganize the .abf files into individual traces using MATLAB, please use the master script m3ha_parse_dclamp_data.m with resavedataflag set to 1. Metadata and analyzed results for all traces are available as both a csv file (dclampdatalog_take4.csv) and a MATLAB .mat file (dclampdatalog_take4.mat).

Master scripts used for analysis were m3ha_parse_dclamp_data.m, m3ha_plot_figure02.m, m3ha_plot_figure04.m.