Cornichon proteins determine the subunit composition of synaptic AMPA receptors.
- Authors
- Herring, Bruce E; Shi, Yun; Suh, Young Ho; Zheng, Chan-Ying; Blankenship, Sabine M; Roche, Katherine W; Nicoll, Roger A
- Year
- 2013
- Journal
- Neuron
- PMID
- 23522044
- DOI
- 10.1016/j.neuron.2013.01.017
- PMCID
- PMC3652566
Cornichon-2 and cornichon-3 (CNIH-2/-3) are AMPA receptor (AMPAR) binding proteins that promote receptor trafficking and markedly slow AMPAR deactivation in heterologous cells, but their role in neurons is unclear. Using CNIH-2 and CNIH-3 conditional knockout mice, we find a profound reduction of AMPAR synaptic transmission in the hippocampus. This deficit is due to the selective loss of surface GluA1-containing AMPARs (GluA1A2 heteromers), leaving a small residual pool of synaptic GluA2A3 heteromers. The kinetics of AMPARs in neurons lacking CNIH-2/-3 are faster than those in WT neurons due to the fast kinetics of GluA2A3 heteromers. The remarkably selective effect of CNIHs on the GluA1 subunit is probably mediated by TARP γ-8, which prevents a functional association of CNIHs with non-GluA1 subunits. These results point to a sophisticated interplay between CNIHs and γ-8 that dictates subunit-specific AMPAR trafficking and the strength and kinetics of synaptic AMPAR-mediated transmission.
CNIH-2 deletion selectively reduces synaptic AMPAR-mediated transmission(A–B) Scatter plots show amplitudes of AMPA and NMDA-eEPSCs for single pairs of neurons from Cnih2fl/fl mice (open circles) and mean ± SEM (filled circles). The scatter plots represent data obtained from acute mouse slices infected with rAAV-CRE-GFP at P0 (red circles) and cultured mouse slices transfected with CRE for 2–3 weeks (black circles). Distributions show a reduction in AMPAR-eEPSC amplitude but no change in NMDAR-eEPSC amplitude. Insets show sample current traces from Control (black) and CRE expressing (green) cells. Bar graphs show mean ± SEM AMPAR and NMDAR-eEPSC amplitudes presented in scatter plots (A, Control [Ctl], 169.2 ± 24.3 pA; CRE, 77.4 ± 10.3 pA; n = 19; *p < 0.001; B, Ctl, 36.5 ± 4.7 pA; CRE, 32.5 ± 5.9 pA; n = 16; p = 0.3). (C) Average AMPAR-eEPSC decay kinetics from pairs of Ctl (black circles) and CRE-infected cells (green circles) (mean Ctl decay ± SEM, 14.4 ± 1.3 ms; mean CRE ± SEM, 11.3 ± 1.4 ms; n = 8; *p < 0.01). Inset shows peak normalized sample traces. (D–E) Bar graphs show mean ± SEM mEPSC amplitude (D, Ctl, 10.0 ± 0.4 pA; n = 8; CRE, 7.6 ± 0.3 pA; n = 8; *p < 0.01) and decay kinetics (E, Ctl, 10.0 ± 0.8 ms; n = 8; CRE, 6.4 ± 0.4 ms; n = 8; *p < 0.01) of Ctl and CRE-infected neurons from Cnih2fl/fl mice. Average traces are shown to the left, and are peak normalized in (E). (F–G) Bar graphs show mean ± SEM AMPAR deactivation (F, Ctl, 3.6 ± 0.2 ms; n = 12; CRE, 2.7 ± 0.2 ms; n = 18; *p < 0.002) and desensitization (G, Ctl, 13.2 ± 0.8 ms; n = 14; CRE, 8.7 ± 0.4 ms; n = 19; *p < 0.0001) from outside-out patches pulled from Ctl and CRE-infected cells and exposed to 1 and 100 ms applications of 1 mM glutamate, respectively. Peak normalized sample traces are shown to the left. (H) Bar graph shows mean ± SEM 1 mM glutamate-induced current amplitudes from outside-out patches pulled from Ctl and CRE-infected cells (Ctl, 870 ± 148 pA; n = 12; CRE, 458 ± 46 pA; n = 17; *p < 0.01). Sample traces are shown to the left. (I) Bar graph shows mean ± SEM IKA/IGlu ratios from outside-out patches pulled from Ctl and CRE-infected cells that were exposed to 1 mM glutamate and 1 mM kainate (Ctl, 0.54 ± 0.03; n = 5; CRE, 0.51 ± 0.03; n = 12; p = 0.56). Sample traces are shown to the left. See also Figure S2.
Deletion of CNIH-2/-3 closely resembles GluA1 elimination(A–B) Scatter plots show amplitudes of AMPA and NMDA-eEPSCs of Ctl and CRE-transfected neurons in cultured slices from Cnih3fl/fl mice. Distributions show no change in AMPAR-eEPSCs or NMDAR-eEPSCs. Insets show sample current traces. Bar graphs show mean ± SEM AMPAR and NMDAR eEPSC amplitudes presented in scatter plots (A, Ctl, 77.0 ± 11.1 pA; ΔCNIH-3, 83.6 ± 14.2 pA; n = 10; p = 1; B, Ctl, 42.5 ± 5.6 pA; ΔCNIH-3, 35.7 ± 8.3 pA; n = 10; p = 0.5). (C–D) Scatter plots showing mean amplitudes of AMPA and NMDA-eEPSCs ± SEM of Ctl and CRE-transfected neurons in cultured slices from Cnih2/3fl/fl mice. Distributions show a reduction in AMPAR-eEPSCs (C, Ctl, 242.5 ± 48.4 pA; ΔCNIH-2/-3, 52.6 ± 9.4 pA; n = 10; *p < 0.01) but no reduction of NMDAR-eEPSCs (D, Ctl, 39.8 ± 5.7 pA; ΔCNIH-2/-3, 34.1 ± 4.7 pA; n = 10; p = 0.2). Insets show sample current traces. (E–F) Bar graphs normalized to Ctl ± SEM summarizing eEPSC data from Cnih2fl/fl, Cnih3fl/fl and Cnih2/3fl/fl mice compared to Gria1fl/fl mice. The light brown bars are published data from the Gria1fl/fl mouse (Lu et al., 2009). (G–H) Bar graphs show mean ± SEM mEPSC amplitude (G, Ctl, 10.0 ± 0.4 pA; n = 8; ΔCNIH-2/-3, 8.2 ± 0.3 pA; n = 7; *p < 0.01) and decay kinetics (H, Ctl, 10.0 ± 0.7 ms; n = 8; ΔCNIH-2/-3, 5.0 ± 0.5 ms; n = 7; *p < 0.001) of Ctl and CRE-infected neurons from Cnih2/3fl/fl mice. Average traces are shown to the left and are peak normalized in (H). (I–J) Bar graphs normalized to Ctl ± SEM summarizing mEPSC data from Cnih2fl/fl, Cnih3fl/fl and Cnih2/3fl/fl mice compared to Gria1fl/fl mice (Lu et al., 2009). (K) Mean ± SEM AMPA-eEPSCs in wild-type (black) and ΔCNIH-2/-3 (green) neurons before and after a whole cell LTP pairing protocol (arrow; Vm = 0 mV, 2 Hz Schaffer collateral stimulation for 90 s normalized to average eEPSC amplitude prior to LTP induction. LTP was severely decreased in ΔCNIH-2/-3 neurons (Ctl, n = 6; ΔCNIH-2/-3, n = 8). Sample traces before and 30–45 min after pairing are shown to the right for Ctl (black) and ΔCNIH-2/-3 (green) neurons. See also Figure S3.
GluA1 is required for CNIH-2’s physical and functional interaction with AMPARs(A–F) Scatter plots show amplitudes of AMPA and NMDA-eEPSCs of Ctl and CNIH-2 shRNA transfected neurons in cultured slices from wild-type, GluA2 KO and GluA1 KO mice. Distributions show that the CNIH-2 shRNA reduces AMPAR-eEPSCs in wild-type (A, Ctl, 102.5 ± 16.5 pA; CNIH-2 shRNA, 52.0 ± 8.6 pA; n = 11; *p < 0.05) and GluA2 KO mice (C, Ctl, 128.9 ± 18.2 pA; CNIH-2 shRNA, 40.2 ± 5.1 pA; n = 10; *p < 0.05) but not GluA1 KO mice (E, Ctl, 54.8 ± 13.1 pA; CNIH-2 shRNA, 58.1 ± 12.3 pA; n = 9; p = 0.4). No effects were seen on NMDAR-eEPSCs (B, Ctl, 44.3 ± 7.0 pA; CNIH-2 shRNA, 42.0 ± 4.5 pA; n=10; p = 1; D, Ctl, 39.4 ± 5.1 pA; CNIH-2 shRNA, 34.9 ± 7.4 pA; n = 9; p = 0.4; F, Ctl, 84.9 ± 18.1 pA; CNIH-2 shRNA, 79.5 ± 23.3 pA; n = 8; p = 0.8). Insets show sample current traces. Bar graphs to the right show mean ± SEM AMPAR and NMDAR-eEPSC amplitudes presented in scatter plots. (G–H) Bar graphs normalized to Ctl ± SEM summarizing AMPAR and NMDAR-eEPSC data from CNIH-2 shRNA transfection of wild-type, GluA2 KO and GluA1 KO mice. (I) Immunoprecipitation of GluA2, GluA1 and CNIH-2 from hippocampal lysates of one wild-type mouse and two GluA1 KO mice using antibodies against GluA2 and GluA2/3. See also Figure S4.
Residual GluA2A3 heteromers can account for the effects of CNIH elimination on AMPAR kinetics(A–B) Immunolabeling of surface GluA1 in untransfected dissociated rat hippocampal neurons (yellow arrows) compared to neurons transfected with either CNIH-2 shRNA (A) or a scrambled shRNA (B) (white arrows). Somatic dark regions are by-products of the confocal image thickness. Dendritic regions of transfected (1) and untransfected (2) neurons are shown at a higher magnification below. (C) Peak normalized sample traces showing AMPAR deactivation in outside-out patches from HEK cells transfected with GluA1A2 and γ-8 or GluA2A3 and γ-8. (D) Bar graph showing mean ± SEM deactivation of GluA1A2γ-8 and GluA2A3γ-8 complexes and the change in AMPAR deactivation kinetics in outside-out patches from ΔCNIH-2 and ΔCNIH-2/-3 CA1 pyramidal neurons (GluA1A2 + γ-8, 3.9 ± 0.4 ms; n = 10; GluA2A3 + γ-8, 1.8 ± 0.2 ms; n = 10; p < 0.001; wild-type. 3.6 ± 0.2 ms; n = 12; ΔCNIH-2, 2.7 ± 0.2 ms; n = 18; *p < 0.002; ΔCNIH-2/-3, 1.6 ± 0.2 ms; n = 6; *p < 0.0001). (E) Bar graph showing mean ± SEM deactivation of GluA2A3γ-8 complexes normalized to GluA1A2γ-8 complexes in outside-out patches from HEK cells (Glu) compared to the percent change in mEPSC decay (mEPSC) in ΔCNIH-2/-3 and ΔGluA1 CA1 pyramidal neurons. See also Figure S5.
CNIH-2 deletion impedes AMPAR trafficking with little effect on other synaptic proteins(A) Bar graphs show mean ± SEM AMPA/NMDA ratios of primary neurons in CA1, dentate gryrus and barrel cortex from wild-type, NexCnih2+/− and NexCnih2−/− mice. (CA1, Ctl, 3.6 ± 0.5; n = 8; NexCnih2+/−, 3.7 ± 0.5; n = 5; NexCnih2−/−, 1.8 ± 0.2; n = 8, *p < 0.001), (DG, Ctl, 3.6 ± 0.3; n = 8; NexCnih2−/−, 1.7 ± 0.2; n = 8) and (BC, Ctl, 2.9 ± 0.5; n = 5; NexCnih2−/−, 1.6 ± 0.2; n = 6; *p < 0.05). AMPA and NMDA sample current traces from CA1 of wild-type and NexCnih2−/− mice normalized to NMDAR current at 150 ms are shown to the left. (B–C) Scatter plots showing that transfection of NexCnih2−/− neurons with CNIH-2 restores the AMPAR-eEPSC amplitude to wild-type levels. Bar graphs to the right of scatter plots show corresponding mean ± SEM eEPSC amplitudes (B, NexCnih2−/−, 53.3 ± 16.9 pA; NexCnih2−/− + CNIH-2, 109.1 ± 29.6 pA; n = 7; *p < 0.05; C, NexCnih2−/−, 60.2 ± 8.7 pA; NexCnih2−/− + CNIH-2, 55.5 ± 7.7 pA; n = 7; p = 0.8). Insets show corresponding sample traces. (D) Immunoblots from hippocampal lysates of wild-type and NexCnih2−/− mice comparing expression levels of synaptic proteins. Bar graph to the right shows average synaptic protein levels in NexCnih2−/− mice normalized to wild-type mice ± SEM (CNIH-2, 0.04 ± 0.008; GluA1, 0.84 ± 0.033; GluA2, 0.82 ± 0.057; γ-8, 0.97 ± 0.062; PSD-95, 0.97 ± 0.039; NR2A, 1.01 ± 0.081; n = 3–5; *p < 0.05). (E) Immunoblots from hippocampal lysates of wild-type NexCnih2−/− and γ-8 KO mice comparing total GluA1, GluA2, γ-8 and CNIH-2 expression levels. Bar graph to the right shows average GluA1, GluA2, γ-8 and CNIH-2 expression levels in NexCnih2−/− and γ-8 KO mice normalized to wild-type mice ± SEM (NexCnih2−/− mice: GluA1, 0.83 ± 0.03; GluA2, 0.89 ± 0.02; γ-8, 0.99 ± 0.05; CNIH-2, 0.05 ± 0.02; n = 3; γ-8 KO mice: GluA1, 0.49 ± 0.05; GluA2, 0.50 ± 0.04; γ-8, 0.03 ± 0.01; CNIH-2, 0.28 ± 0.02; n = 3; *p < 0.05). (F) Glycosylation analysis of GluA1 and GluA2 in wild-type and NexCnih2−/− mice. The representative blot to the left shows the relative amount of mature GluA1 receptor subunits (blue arrows) to immature GluA1 subunits (red arrows) in hippocampal lysates from wild-type and NexCnih2−/− mice. Bar graph to the right shows the average ratio of immature to mature GluA1 and GluA2 subunits in NexCnih2−/− mice normalized to wild-type mice ± SEM (GluA1, 1.99 ± 0.28; GluA2, 1.70 ± 0.13; n = 3–5; *p < 0.05). (G) Biotinylation analysis of GluA1, GluA2, γ-8 and CNIH-2 in dissociated hippocampal neurons. See also Figure S6.
γ γγ-8 blocks CNIH-2’s functional interaction with GluA2 but not GluA1(A) Bar graph shows mean ± SEM deactivation kinetics of GluA1 homomers expressed in HEK cells alone, with γ-8, with CNIH-2 and with γ-8 and CNIH-2 (Ai, GluA1, 1.8 ± 0.2 ms, n = 10; GluA1 + γ-8, 4.9 ± 0.3 ms, n = 8; GluA1 + CNIH-2, 8.7 ± 0.6 ms, n = 11; GluA1 + γ-8 + CNIH-2, 9.4 ± 0.7 ms, n = 12). Mean ± SEM IKA/IGlu ratios for GluA1 + γ-8 and GluA1 + γ-8 + CNIH-2 were also compared (Aii, GluA1 + γ-8, 0.57 ± 0.03, n = 8; GluA1 + γ-8 + CNIH-2, 0.54 ± 0.05, n = 5). (B–C) Bar graphs show mean ± SEM deactivation kinetics of GluA2(Q) homomers and GluA1A2(R) heteromers expressed in HEK cells alone, with γ-8, with CNIH-2 and with γ-8 and CNIH-2 (B, GluA2(Q), 1.2 ± 0.2 ms, n = 8; GluA2(Q) + γ-8, 4.5 ± 1.0 ms, n = 4; GluA2(Q) + CNIH-2, 10.0 ± 1.5 ms, n = 7; GluA2(Q) + γ-8 + CNIH-2, 6.0 ± 0.7 ms, n = 6) (C, GluA1A2(R), 1.7 ± 0.4 ms, n = 6; GluA1A2(R) + γ-8, 3.9 ± 0.4 ms, n = 10; GluA1A2(R) + CNIH-2, 11.7 ± 1.0 ms, n = 6; GluA1A2(R) + γ-8 + CNIH-2, 5.7 ± 0.5 ms, n = 9). Corresponding peak normalized sample traces are shown to the left of bar graphs. See also Figure S7.
CNIH-2 slows synaptic AMPAR currents in the absence of γγ γ-8(A–B) Bar graphs show mean ± SEM mEPSC amplitude (A) and decay (B) of wild-type, NexCnih2−/−, CNIH-2 overexpressing (OE), γ-8 KO and γ-8 KO + CNIH-2 CA1 neurons in slice culture (A, wild-type, 17.4 ± 1.6 pA; n = 8; NexCnih2−/−, 9.5 ± 0.5 pA; n = 9; CNIH-2 OE, 17.3 ± 1.6 pA; n = 5; γ-8 KO, 10.7 ± 0.9 pA; n = 9; γ-8 KO + CNIH-2, 19.1 ± 3.5 pA; n = 7; *p < 0.05) (B, wild-type, 6.3 ± 0.4 ms; n = 8; NexCnih2−/−, 4.4 ± 0.3 ms; n = 9; CNIH-2 OE, 6.4 ± 0.4 ms; n = 5; γ-8 KO, 7.8 ± 0.6 ms; n = 9; γ-8 KO + CNIH-2, 14.2 ± 0.63 ms; n = 7; *p < 0.05). Select color-matched sample traces are shown above bar graphs. Sample traces in (B) are peak normalized. Note that compared to acute slices baseline mEPSC amplitude is larger and mEPSC kinetics are faster in slice culture (see Supplemental Experimental Procedures).
Model of CNIH and γ γγ-8 interactions with AMPARs(A) GluA1 AMPAR subunits simultaneously associate with CNIH proteins and TARP γ-8. Therefore, we propose surface tetrameric GluA1 homomers associate with 4 γ-8 molecules and 1–4 CNIH molecules. (B) CNIH protein association with GluA2 AMPAR subunits appears to be prevented by γ-8. Therefore, in the presence of γ-8, we propose surface GluA2 homomers associate with 4 γ-8 molecules and 0 CNIH molecules. (C) Because of GluA1 and GluA2’s respective relationships with γ-8 and CNIH proteins, we propose surface GluA1A2 heteromers associate with 4 γ-8 molecules and 1–2 CNIH molecules. (D) Because GluA1 is required for the physical association of CNIH proteins but not γ-8 with AMPARs in neurons, we propose surface GluA2/3 heteromers associate with 4 γ-8 molecules and 0 CNIH molecules. (E) In neurons CNIH proteins selectively promote the trafficking of GluA1A2 heteromers but not GluA2A3 heteromers to the neuronal surface. γ-8 prevents CNIH interaction with non-GluA1 subunits and provides a mechanism for the subunit specific action of CNIH on GluA1A2 receptor trafficking. Overexpression of CNIH in wild-type neurons does not slow AMPAR gating kinetics indicating CNIH cannot displace γ-8 on non-GluA1 subunits. Together these data suggest a model whereby in the ER/Golgi γ-8 associates with AMPARs prior to CNIH (1) thus limiting subsequent CNIH interactions to only GluA1 subunits, which uniquely associate with both γ-8 and CNIH (2). CNIH proteins would then selectively enable the forward trafficking of GluA1A2 heteromers to the neuronal surface (3). CNIH deletion prevents GluA1A2 receptors from leaving the ER/Golgi.
| Name | Type |
|---|---|
| AAV-CRE-GFP local | drug |
| Alexa Fluor 555 local | drug |
| altered kinetics local | phenotype |
| AMPA mEPSC decay kinetics local | phenotype |
| AMPAR | drug |
| AMPAR deactivation local | phenotype |
| AMPAR desensitization local | phenotype |
| AMPAR-eEPSC local | phenotype |
| AMPAR-eEPSC amplitude local | phenotype |
| AMPAR-eEPSC rectification local | phenotype |
| AMPAR-eEPSCs local | drug |
| AMPAR-EPSC decay local | phenotype |
| AMPAR EPSC kinetics local | phenotype |
| AMPAR-mediated responses local | phenotype |
| AMPAR/NMDAR eEPSC ratio local | phenotype |
| ataxic mouse stargazer local | phenotype |
| barrel cortex | anatomy |
| CA1 | anatomy |
| CA1 pyramidal neuron local | anatomy |
| CA1 pyramidal neurons | anatomy |
| CACNG2 | gene |
| CACNG8 | gene |
| cerebellar granule cells | anatomy |
| cerebellar granule neuron local | anatomy |
| Cerebellar granule neuron local | anatomy |
| cis-Golgi local | anatomy |
| CNI local | gene |
| CNIH local | gene |
| Cnih2 local | gene |
| CNIH-2 local | gene |
| CNIH2 local | gene |
| CNIH2/3 conditional knockout local | variant |
| Cnih2/3fl/fl local | cohort |
| Cnih2/3fl/fl mice local | cohort |
| Cnih2fl/fl local | variant |
| Cnih2fl/fl mice local | cohort |
| CNIH-2 shRNA local | drug |
| Cnih3 | gene |
| Cnih3fl/fl local | variant |
| Cnih3fl/fl mice local | cohort |
| CNIH KO local | cohort |
| Cre | gene |
| cyclothiazide | drug |
| deactivation local | phenotype |
| Deactivation kinetics of surface AMPARs local | phenotype |
| deactivation of glutamate-evoked currents local | phenotype |
| dentate granule neuron local | anatomy |
| dentate gyrus | anatomy |
| desensitization of glutamate-evoked currents local | phenotype |
| Dlg4 | gene |
| Egfr | gene |
| Endo H local | drug |
| endoplasmic reticulum | anatomy |
| ERV14P local | gene |
| extrasynaptic currents local | phenotype |
| fast kinetics local | phenotype |
| FLP deleter line local | cohort |
| forebrain pyramidal neurons local | anatomy |
| gating kinetics local | phenotype |
| GFP | drug |
| GluA1A2 AMPAR local | drug |
| GluA1A2 heteromer local | drug |
| GluA1A2γ-8 complex local | drug |
| GluA1 antibody local | drug |
| GluA1 conditional KO mice local | cohort |
| GluA1 KO mice local | cohort |
| GluA2A3 receptor local | drug |
| GluA2A3γ-8 complex local | drug |
| GluA2(Q) local | variant |
| GluA2(R) local | variant |
| glutamate | drug |
| granule cells | anatomy |
| GRIA1 | gene |
| GRIA1 conditional knockout local | variant |
| Gria1fl/fl local | cohort |
| GRIA1 KO mice local | cohort |
| GRIA2 | gene |
| GRIA2 KO mice local | cohort |
| GRIA2(Q) local | variant |
| GRIA3 | gene |
| GRIA4 | gene |
| GRIN2A | gene |
| HEK cells local | cohort |
| hippocampus | anatomy |
| IKA/IGlu ratio local | phenotype |
| kainate | drug |
| lack of synaptic GluA1-containing AMPARs local | phenotype |
| layer 2/3 neocortical neuron local | anatomy |
| long-term potentiation | phenotype |
| loss of AMPAR currents local | phenotype |
| loss of total GluA1 protein expression local | phenotype |
| LTP | phenotype |
| mEPSC amplitude local | phenotype |
| mEPSC decay local | phenotype |
| mEPSC decay kinetics local | phenotype |
| mEPSC frequency local | phenotype |
| mossy cells local | anatomy |
| neocortex | anatomy |
| NexCnih2−/− brain local | cohort |
| NexCnih2+/− mice local | cohort |
| NexCnih2−/− mice local | cohort |
| NEX-CRE mice local | cohort |
| Nex-CRE mouse line local | cohort |
| NEX-CRE mouse line local | cohort |
| NMDAR | drug |
| NMDAR-eEPSC local | phenotype |
| NMDAR-eEPSC amplitude local | phenotype |
| P17–P21 mice local | cohort |
| P6–P9 mice local | cohort |
| paired-pulse ratio local | phenotype |
| PNGase F local | drug |
| Purkinje cells | anatomy |
| rat hippocampal neurons local | cohort |
| rats | cohort |
| Reduced AMPA/NMDA ratio local | phenotype |
| reduced AMPAR-eEPSC local | phenotype |
| Reduced AMPAR-eEPSC local | phenotype |
| reduced current amplitudes local | phenotype |
| resensitization local | phenotype |
| Schaffer collaterals | anatomy |
| scrambled shRNA local | drug |
| Sepharose beads local | drug |
| SHISA9 local | gene |
| slice cultures local | cohort |
| slowing of deactivation local | phenotype |
| speeding of AMPAR kinetics local | phenotype |
| stargazer mice local | cohort |
| stratum radiatum | anatomy |
| synaptic changes local | phenotype |
| synaptic plasticity deficits local | phenotype |
| Triton X-100 | drug |
| TTX | drug |
| unchanged AMPAR-eEPSC local | phenotype |
| unchanged AMPAR mEPSC kinetics local | phenotype |
| unchanged NMDAR eEPSC local | phenotype |
| Unchanged NMDAR-eEPSC local | phenotype |
| Wild-type brain local | cohort |
| wild-type mice | cohort |
| wild-type neurons local | cohort |
| γ-8/AMPAR stoichiometry local | phenotype |
| γ-8 KO mice local | cohort |
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| Oxytocin signaling is necessary for synaptic maturation of adult-born neurons. | Pekarek BT et al. | — | 2022 | → |
| Schizophrenia-associated SAP97 mutations increase glutamatergic synapse strength in the dentate gyrus and impair contextual episodic memory in rats. | Kay Y et al. | — | 2022 | → |
| Slow excitatory synaptic currents generated by AMPA receptors. | Pampaloni NP et al. | — | 2022 | → |
| Structural insights into function of ionotropic glutamate receptors. | Yelshanskaya MV et al. | — | 2022 | → |
| Synaptic Disruption by Soluble Oligomers in Patients with Alzheimer's and Parkinson's Disease. | Gutierrez BA et al. | — | 2022 | → |
| The role of AMPAR lateral diffusion in memory. | Choquet D et al. | — | 2022 | → |
| AMPA receptors in the synapse: Very little space and even less time. | Baranovic J | — | 2021 | → |
| AMPA receptor structure and auxiliary subunits. | Kamalova A et al. | — | 2021 | → |
| An optogenetic method for investigating presynaptic molecular regulation. | Kay Y et al. | — | 2021 | → |
| Auxiliary subunits of the AMPA receptor: The Shisa family of proteins. | Abdollahi Nejat M et al. | — | 2021 | → |
| Building of AMPA-type glutamate receptors in the endoplasmic reticulum and its implication for excitatory neurotransmission. | Schwenk J et al. | — | 2021 | → |
| Gating and modulation of a hetero-octameric AMPA glutamate receptor. | Zhang D et al. | — | 2021 | → |
| Genome-Wide Association Analysis of Neonatal White Matter Microstructure. | Zhang J et al. | — | 2021 | → |
| Hippocampal AMPA receptor assemblies and mechanism of allosteric inhibition. | Yu J et al. | — | 2021 | → |
| Modulation of information processing by AMPA receptor auxiliary subunits. | Jacobi E et al. | — | 2021 | → |
| Sex Differences in the Role of CNIH3 on Spatial Memory and Synaptic Plasticity. | Frye HE et al. | — | 2021 | → |
| Slow AMPA receptors in hippocampal principal cells. | Pampaloni NP et al. | — | 2021 | → |
| Structure, Function, and Pharmacology of Glutamate Receptor Ion Channels. | Hansen KB et al. | — | 2021 | → |
| X-linked neonatal-onset epileptic encephalopathy associated with a gain-of-function variant p.R660T in GRIA3. | Sun JH et al. | — | 2021 | → |
| A Screen for Gene Paralogies Delineating Evolutionary Branching Order of Early Metazoa. | Erives A et al. | — | 2020 | → |
| Glutamatergic Receptor Trafficking and Delivery: Role of the Exocyst Complex. | Lira M et al. | — | 2020 | → |
| PORCN Negatively Regulates AMPAR Function Independently of Subunit Composition and the Amino-Terminal and Carboxy-Terminal Domains of AMPARs. | Wei M et al. | — | 2020 | → |
| A Conserved Tyrosine Residue in Slitrk3 Carboxyl-Terminus Is Critical for GABAergic Synapse Development. | Li J et al. | — | 2019 | → |
| AMPA Receptor Auxiliary Proteins of the CKAMP Family. | von Engelhardt J | — | 2019 | → |
| AMPA receptors and their minions: auxiliary proteins in AMPA receptor trafficking. | Bissen D et al. | — | 2019 | → |
| An ER Assembly Line of AMPA-Receptors Controls Excitatory Neurotransmission and Its Plasticity. | Schwenk J et al. | — | 2019 | → |
| Coordination of AMPA receptor trafficking by Rab GTPases. | Hausser A et al. | — | 2019 | → |
| Folding unpredicted. | Schwenk J et al. | — | 2019 | → |
| How to Avoid a No-Deal ER Exit. | Anelli T et al. | — | 2019 | → |
| Structures of the AMPA receptor in complex with its auxiliary subunit cornichon. | Nakagawa T | — | 2019 | → |
| The AMPA Receptor Subunit GluA1 is Required for CA1 Hippocampal Long-Term Potentiation but is not Essential for Synaptic Transmission. | Terashima A et al. | — | 2019 | → |
| An Intellectual Disability-Related Missense Mutation in Rac1 Prevents LTP Induction. | Tian C et al. | — | 2018 | → |
| CKAMP44 modulates integration of visual inputs in the lateral geniculate nucleus. | Chen X et al. | — | 2018 | → |
| mGlu<sub>1</sub> and mGlu<sub>5</sub> modulate distinct excitatory inputs to the nucleus accumbens shell. | Turner BD et al. | — | 2018 | → |
| Multiple Membrane Transporters and Some Immune Regulatory Genes are Major Genetic Factors to Gout. | Zhu W et al. | — | 2018 | → |
| Phosphorylation of the AMPAR-TARP Complex in Synaptic Plasticity. | Park J | — | 2018 | → |
| Postsynaptic localization and regulation of AMPA receptors and Cav1.2 by β2 adrenergic receptor/PKA and Ca<sup>2+</sup>/CaMKII signaling. | Patriarchi T et al. | — | 2018 | → |
| SAP102 regulates synaptic AMPAR function through a CNIH-2-dependent mechanism. | Liu M et al. | — | 2018 | → |
| The AMPA Receptor Code of Synaptic Plasticity. | Diering GH et al. | — | 2018 | → |
| Ablation of SNX6 leads to defects in synaptic function of CA1 pyramidal neurons and spatial memory. | Niu Y et al. | — | 2017 | → |
| Control of AMPA receptor activity by the extracellular loops of auxiliary proteins. | Riva I et al. | — | 2017 | → |
| Diversity in AMPA receptor complexes in the brain. | Jacobi E et al. | — | 2017 | → |
| Engineering defined membrane-embedded elements of AMPA receptor induces opposing gating modulation by cornichon 3 and stargazin. | Hawken NM et al. | — | 2017 | → |
| Ferric Chelate Reductase 1 Like Protein (FRRS1L) Associates with Dynein Vesicles and Regulates Glutamatergic Synaptic Transmission. | Han W et al. | — | 2017 | → |
| GARLH Family Proteins Stabilize GABA<sub>A</sub> Receptors at Synapses. | Yamasaki T et al. | — | 2017 | → |
| GSG1L regulates the strength of AMPA receptor-mediated synaptic transmission but not AMPA receptor kinetics in hippocampal dentate granule neurons. | Mao X et al. | — | 2017 | → |
| Ionotropic AMPA-type glutamate and metabotropic GABA<sub>B</sub> receptors: determining cellular physiology by proteomes. | Bettler B et al. | — | 2017 | → |
| Structural and Functional Architecture of AMPA-Type Glutamate Receptors and Their Auxiliary Proteins. | Greger IH et al. | — | 2017 | → |
| Subunit-specific synaptic delivery of AMPA receptors by auxiliary chaperone proteins TARPγ8 and GSG1L in classical conditioning. | Keifer J et al. | — | 2017 | → |
| The Inhibitory Effect of α/β-Hydrolase Domain-Containing 6 (ABHD6) on the Surface Targeting of GluA2- and GluA3-Containing AMPA Receptors. | Wei M et al. | — | 2017 | → |
| Transcriptional Dependencies in Diffuse Intrinsic Pontine Glioma. | Nagaraja S et al. | — | 2017 | → |
| An unrecognized function for COPII components in recruiting the viral replication protein BMV 1a to the perinuclear ER. | Li J et al. | — | 2016 | → |
| CaMKII Phosphorylation of TARPγ-8 Is a Mediator of LTP and Learning and Memory. | Park J et al. | — | 2016 | → |
| Distinct stages in the recognition, sorting, and packaging of proTGFα into COPII-coated transport vesicles. | Zhang P et al. | — | 2016 | → |
| Distinct Structural Pathways Coordinate the Activation of AMPA Receptor-Auxiliary Subunit Complexes. | Dawe GB et al. | — | 2016 | → |
| Evidence of CNIH3 involvement in opioid dependence. | Nelson EC et al. | — | 2016 | → |
| Genome-wide association study of clinically defined gout identifies multiple risk loci and its association with clinical subtypes. | Matsuo H et al. | — | 2016 | → |
| GluA1 signal peptide determines the spatial assembly of heteromeric AMPA receptors. | He XY et al. | — | 2016 | → |
| GSG1L suppresses AMPA receptor-mediated synaptic transmission and uniquely modulates AMPA receptor kinetics in hippocampal neurons. | Gu X et al. | — | 2016 | → |
| Inhibitory RNA Aptamers of Tau Oligomerization and Their Neuroprotective Roles against Proteotoxic Stress. | Kim JH et al. | — | 2016 | → |
| Modulation of excitatory neurotransmission by neuronal/glial signalling molecules: interplay between purinergic and glutamatergic systems. | Köles L et al. | — | 2016 | → |
| Porcupine Controls Hippocampal AMPAR Levels, Composition, and Synaptic Transmission. | Erlenhardt N et al. | — | 2016 | → |
| Synaptic AMPA receptor composition in development, plasticity and disease. | Henley JM et al. | — | 2016 | → |
| The Transmembrane Domain Mediates Tetramerization of α-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid (AMPA) Receptors. | Gan Q et al. | — | 2016 | → |
| Depletion of the AMPAR reserve pool impairs synaptic plasticity in a model of hepatic encephalopathy. | Schroeter A et al. | — | 2015 | → |
| Identification of rice cornichon as a possible cargo receptor for the Golgi-localized sodium transporter OsHKT1;3. | Rosas-Santiago P et al. | — | 2015 | → |
| Modulation of non-NMDA receptor gating by auxiliary subunits. | Howe JR | — | 2015 | → |
| Multiple forms of metaplasticity at a single hippocampal synapse during late postnatal development. | McHail DG et al. | — | 2015 | → |
| Spatiotemporal dynamics of the postnatal developing primate brain transcriptome. | Bakken TE et al. | — | 2015 | → |
| Synaptic localization of neurotransmitter receptors: comparing mechanisms for AMPA and GABAA receptors. | Martenson JS et al. | — | 2015 | → |
| TARP γ-8 glycosylation regulates the surface expression of AMPA receptors. | Zheng CY et al. | — | 2015 | → |
| The intellectual disability protein RAB39B selectively regulates GluA2 trafficking to determine synaptic AMPAR composition. | Mignogna ML et al. | — | 2015 | → |
| Ablation of ErbB4 from excitatory neurons leads to reduced dendritic spine density in mouse prefrontal cortex. | Cooper MA et al. | — | 2014 | → |
| Auxiliary subunits: shepherding AMPA receptors to the plasma membrane. | Haering SC et al. | — | 2014 | → |
| Cornichon2 dictates the time course of excitatory transmission at individual hippocampal synapses. | Boudkkazi S et al. | — | 2014 | → |
| Differential requirement for NMDAR activity in SAP97β-mediated regulation of the number and strength of glutamatergic AMPAR-containing synapses. | Liu M et al. | — | 2014 | → |
| Expression mechanisms underlying long-term potentiation: a postsynaptic view, 10 years on. | Granger AJ et al. | — | 2014 | → |
| Functional properties of extrasynaptic AMPA and NMDA receptors during postnatal hippocampal neurogenesis. | Schmidt-Salzmann C et al. | — | 2014 | → |
| Interaction proteomics reveals brain region-specific AMPA receptor complexes. | Chen N et al. | — | 2014 | → |
| Intracellular Ca²⁺ and not the extracellular matrix determines surface dynamics of AMPA-type glutamate receptors on aspiny neurons. | Klueva J et al. | — | 2014 | → |
| Molecular dissection of the interaction between the AMPA receptor and cornichon homolog-3. | Shanks NF et al. | — | 2014 | → |
| Regional diversity and developmental dynamics of the AMPA-receptor proteome in the mammalian brain. | Schwenk J et al. | — | 2014 | → |
| Retromer mediates a discrete route of local membrane delivery to dendrites. | Choy RW et al. | — | 2014 | → |
| Transcriptional analysis of a whole-body form of long-term habituation in Aplysia californica. | Holmes G et al. | — | 2014 | → |
| AMPARs and synaptic plasticity: the last 25 years. | Huganir RL et al. | — | 2013 | → |
| A role of TARPs in the expression and plasticity of calcium-permeable AMPARs: evidence from cerebellar neurons and glia. | Bats C et al. | — | 2013 | → |
| Conduits of life's spark: a perspective on ion channel research since the birth of neuron. | Isacoff EY et al. | — | 2013 | → |
| Cornichons control ER export of AMPA receptors to regulate synaptic excitability. | Brockie PJ et al. | — | 2013 | → |
| Distance-dependent scaling of AMPARs is cell-autonomous and GluA2 dependent. | Shipman SL et al. | — | 2013 | → |
| SynDIG1 promotes excitatory synaptogenesis independent of AMPA receptor trafficking and biophysical regulation. | Lovero KL et al. | — | 2013 | → |