Article Figures & Data
Figures
- Fig. 1.
Normal number of inhibitory inputs in GAD 65 KO mice. A, Stimulation in layer IV effectively recruits the maximal IPSCs in layer II/III cells. Diagram on theleft depicts stimulation–recording configuration.Traces are examples of maximal responses evoked by layer IV stimulation (1), lateral stimulation (2), and layer IV and lateral stimulation together (1 + 2). B,C, Similar relationship between stimulus intensity and IPSC magnitude in GAD 65 KO mice and their wild-type (WT) littermates. A, Example IPSCs evoked by a series of stimulus of increasing intensity (5, 10, 20, 40, 80, and 160 mA) recorded in layer II/III pyramidal cells from wild type (left) and an age-matched GAD 65 KO littermate (right). B, Relationship between IPSC magnitude and stimulus intensity for wild type (open circles; 11 cells, 6 mice) and GAD 65 KO littermates (filled circles; 11 cells, 6 mice). Indicated on theright are the maximal IPSC amplitudes (obtained at 160 mA) for all individual experiments.
- Fig. 2.
Reduced efficacy of GABAergic synaptic transmission during repetitive activation in GAD 65 KO mice.A, Reduced response to tetanic stimulation (100 pulses at 1 Hz) in cells from GAD 65 KO mice. Superimposed traces represent the average of the responses of eight cells from GAD 65 KO mice (thick trace) and 11 cells from age-matched wild-type (WT) littermate (thin trace) mice. Stimulation intensity was adjusted to evoke single IPSCs of similar amplitude in both genotypes. Theinset shows the same average responses at higher temporal resolution. The total charge flow during the tetanus is shown on the right bar graph. The response of cell was integrated and then averaged across genotypes. B, Examples of responses evoked by 15 pulse trains delivered at 30 Hz (top) and 50 Hz (bottom) in cells from a GAD 65 KO (thick trace) mouse and its age-matched wild-type littermate (thin trace). Thetraces (averages of 4 responses) have been normalized to the response to the first pulse of the train. C, Average attenuation of the IPSC amplitude during 15 pulse trains delivered at 1 Hz (triangles), 30 Hz (circles), and 50 Hz (squares). Results from wild type are shown on theleft, and results from GAD 65 KOs are on theright. The curves are single exponentials that give the best fit to the data. D, Relative amplitudes of IPSC at steady state (average of the last 3 responses of a train) across different stimulation frequencies. Open symbols, Wild type; filled symbols, GAD 65 KO.
- Fig. 3.
Induction of LTD with 1 Hz LFS is impaired in the visual cortex but not in the CA1 region of GAD 65 KO mice. The graphs depict average changes in the evoked field potentials induced by LFS (1 Hz, 15 min) in slices of visual cortex (A) and CA1 (B) prepared from 3-week-old wild-type (WT) mice (open circles) and their GAD 65 KO littermates (filled circles). The LTD magnitude for each individual experiment (measured 1 hr after LFS) is shown at the right of each graph. Example field potential traces from experiments performed in wild-type (top) and KO (bottom) mice are shown in the right. The superimposed traces are averages of four consecutive responses recorded 1 min before (thin traces) and 1 hr after (thick traces) LFS.
- Fig. 4.
Chronic but not acute application of diazepam (DZ) restores LTD in the visual cortex of GAD 65 KO mice. A, LFS does not induce LTD in slices from GAD 65 KO in control conditions (DMSO; open circles) or when 15 μm diazepam was continuously bath applied from 20 min before experiment (filled circles). B, Pretreatment with diazepam (10 mg/kg daily; 5–6 d) abolishes the differences in LTD between wild-type (open circles) and GAD 65 KO (filled circles) mice. As in Figure 3, the results from all individual experiments are depicted on theright of each graph. Representative field potential traces for each experimental condition are shown on the far right. The superimposed traces are averages of four consecutive responses recorded 1 min before (thin traces) and 1 hr after (thick traces) LFS.
