Figure 6 | Scientific Reports

Figure 6

From: Strictly regulated agonist-dependent activation of AMPA-R is the key characteristic of TAK-653 for robust synaptic responses and cognitive improvement

Figure 6

Effect of TAK-653, LY451646, and AMPA on AMPA-R-mediated EPSPs in prefrontal cortical slice. (A) In the presence of bicuculline (20 μM), CGP52422 (10 μM), and APV (50 μM) to block GABAA and B and NMDA receptors, respectively, single stimulation of glutamatergic afferents to PFC pyramidal neurons evoked polysynaptic EPSPs to induce action potential spiking. Addition of 10 μM TAK-653 for 10 min enhanced the suprathreshold response, resulting in the prolongation of action potentials trains. This response was abolished by the AMPA receptor antagonist NBQX (10 μM). (B, C) Effects of TAK-653 on the number of spikes (B) and duration (C) of AMPA-R-mediated EPSPs. Data were represented as mean ± SEM (n = 6–10). (D, E) Effects of LY451646 on the number of spikes (D) and duration (E) of AMPA-R-mediated EPSPs. (F) Addition of 30 μM LY451646 for 10 min enhanced the suprathreshold response. Perfusion changes from LY451646 to TAK653 caused further augmentation of spike number. (G, H) Effects of TAK-653 after removal of LY451646 on the number of spikes (G) and duration (H) of AMPA-R-mediated EPSPs. Data were represented as mean ± SEM (n = 6–9). Statistical significance between LY451646 and TAK-653 was determined by a paired t test with significance set at #P ≤ 0.05. (I) Application of 0.3 μM AMPA for 5 min diminished the suprathreshold response (n = 6).

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