Article Figures & Data
Figures
- Figure 1.
GluK1 KARs regulate spontaneous interneuronal firing frequency in CA3 at P3–P5 but not at P14–P16. a , Left, Data from on-cell recordings in interneurons show that the mean AP firing frequency of interneurons in P3–P5 GluK1−/− mice (n = 25), was significantly lower than that of wild types (p < 0.05, n = 16). Sample traces from WT and GluK1 −/− mice and summary statistics for the P3–P5 data are shown. Right, Corresponding data from P14–P16 animals, showing that there was no difference in AP firing rate between WT (n = 8) and GluK1 −/− (n = 10) mice at this age. b , c , Sample traces ( b ) and summary plot ( c ) (black, WT; gray, GluK1 −/− ) showing dramatic attenuation of AP firing rate in P3–P5 WT (p = 0.0007, n = 10) but not in GluK1−/− mice (n = 8, p = 0.65) upon application of the GluK1 antagonist, LY 382884. d , Summary statistics for the effect of LY 382884 on interneuronal firing rate in WT (left) and GluK1 −/− mice (right). *p < 0.05; ***p < 0.005.
- Figure 2.
KARs regulate interneuronal excitability and mAHP at P3–P5. a , Pooled data from current-clamp experiments showing the firing of P3–P5 interneurons at depolarizing steps of varying amplitude (500–1000 ms, ΔI = 20 pA). In WT (black circles, n = 36), the firing is attenuated by the GluK1 antagonist LY 382884 (black triangles, n = 8). In GluK1 −/− mice the firing is significantly lower compared with WT (gray squares with solid line, n = 40). b , Representative traces from current-clamp experiments showing firing in WT, GluK1−/−, and WT + LY 382884 interneurons at a 80 pA/500 ms depolarizing step. Note the prominent afterhyperpolarization in GluK1 −/−. c , Summary statistics for the interspike trajectory. d , Pooled data from current-clamp experiments showing the firing of P14–P16 interneurons at depolarizing steps of varying amplitude (500–1000 ms, ΔI = 20 pA). There are no significant differences between the firing rates in WT (black circles, n = 5) and WT + LY 382884 mice (black triangles, n = 7). e , Representative traces from current-clamp experiments showing firing in WT and WT + LY 382884 interneurons at a 80 pA/500 ms depolarizing step. ***p < 0.001.
- Figure 3.
Tonic activity of KAR downregulates apamin-sensitive component of ImAHP at P3–P5 but not at P14–P16. a , Whole-cell voltage-clamp data showing sample ImAHP traces before and after wash-in of apamin and summary plot for the effect of apamin on the afterhyperpolarizing current in P3–P5 interneurons (n = 5, p < 0.005). b , Representative traces and summary plot for the effect of LY 382884 on the afterhyperpolarizing current at P3–P5 (n = 18, p < 0.005). c , Example traces and pooled data showing that ATPA decreases the ImAHP in P3–P5 interneurons (n = 14, p < 0.005). d , Summary data showing the combined effects of LY 382884, ATPA, and apamin on the ImAHP in P3–P5 interneurons. Note that the effect of apamin on the ImAHP is bigger after application of LY 382884 and that the effects of ATPA and apamin are mutually occlusive (ATPA + apamin n, = 5; apamin + ATPA, n = 4; LY 382884 + apamin n = 4). e , Pooled data showing the developmental regulation of the apamin-sensitive component of the ImAHP (P3–P5, n = 8; P14–P16, n = 7; p < 0.05). Data and traces have been obtained by subtracting the ImAHP in the presence of apamin from control current before application of the drug. f , Data showing that in young adult mice (P14–P16) neither GluK1 agonist ATPA nor the antagonist LY 382884 affects the ImAHP amplitude, while apamin still strongly depresses the current (n = 4; p < 0.005). g , Summary data showing the effects of LY 382884, ATPA, and apamin on the ImAHP in P14–P16 interneurons. *p < 0.05; **p < 0.01.
- Figure 4.
Mechanism for tonic regulation of the mAHP a , Representative traces and summary plot for the effect of ATPA after blockade of AMPAR, NMDAR, GABAA, metabotropic glutamate, 5-HT, NE, DA, ACh, and CB1 receptors (n = 6, p < 0.05). b , Representative traces and summary plot for the effect of glutamate scavenger and LY 382884 on the afterhyperpolarizing current in P3–P5 interneurons. (n = 6, p < 0.01). c , Representative traces and summary plot for the lack of effect of the glutamate scavenger on the afterhyperpolarizing current at P14–P16 (n = 5, p > 0.05). Recordings ( a and b ) were done in the presence of antagonists for AMPA, NMDA, mGlu, GABAA, and GABAB receptors. d , Example traces and pooled data from P3–P5 mice showing that inhibition of G-protein-mediated signaling by intracellular application of GDPβS accentuates ImAHP (n = 4, p < 0.05). GDPβS occludes the effect of ATPA on the afterhyperpolarizing current. e , Sample traces and summary statistics demonstrating the lack of effect of GDPβS and ATPA on ImAHP in P14–P16 mice (n = 5). f , Representative traces and summary plot for the lack of effect of PKC inhibitor BIS on the afterhyperpolarizing current in P3–P5 interneurons (n = 9) and the effect of ATPA after BIS (p < 0.05, n = 6).
- Figure 5.
The effect of apamin on network activity and interneuronal firing. a , Sample traces and summary plot of whole-cell current-clamp recordings showing that apamin increases the occurrence of synchronous network bursts recorded in P3–P5 interneurons (p < 0.05, n = 8). b , Data from on-cell recordings in P3–P5 interneurons showing the effect of apamin on spontaneous AP firing frequency in WT (n = 8) and GluK1−/− mice (n = 6). Summary graph on the right shows that the effect of apamin on mean firing frequency was significantly (p < 0.01) bigger in GluK1−/− interneurons. c , Data from on-cell recordings in P14–P16 interneurons, showing the effect of apamin on spontaneous AP firing frequency in WT (n = 6) and GluK1 −/− mice (n = 6). Summary graph on the right shows the effect of apamin on mean firing frequency.
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