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. 2017 Jan 18;93(2):409–424. doi: 10.1016/j.neuron.2016.11.046

Figure 5.

Figure 5

GluA3 Plasticity Occurs through cAMP-Dependent Changes of Single-Channel Conductance and Open Probability

(A) Example traces of cell-attached, single-channel recordings of GluA2/GluA3 AMPARs in PCs of GluA1-KO mice. Under basal conditions (light red), the vast majority of the openings of GluA2/GluA3 AMPARs occur at the low conductance level (O1), but in the presence of FSK, the amount of openings in the higher conductance levels (O2-3) increases (red).

(B) Count-versus-amplitude histograms of the events detected in the representative recordings shown in (A) illustrate the uneven distribution of events across the different conductance levels in the absence (light red) or presence (red) of FSK.

(C) The opening durations (dwell time) of the same events shown in (A) and (B) were unchanged after FSK application. However, the duration of the closed-state times was reduced, suggesting a net increase in the total number of openings produced by GluA2/GluA3 channels in the presence of FSK.

(D) Overall quantification of GluA2/GluA3 single-channel recordings shows that the conductance significantly increased in the presence of FSK, yet the conductance per open state remained unchanged.

(E) FSK significantly changed the distribution of GluA2/GluA3 AMPAR events, as revealed by a significant decrease of events at O1 state and a significant increase in events at O2 and O3 states. The reduction of the closed-state time shown in (C) was translated into a significant increase of the open-channel probability.

(F) The classical model of GluA1-subunit-dependent LTP in pyramidal cells (see Introduction) does not prove valid at PF-PC synapses. Note that the absolute numbers of subsets of both GluA1/GluA2 and GluA2/GluA3 AMPARs are unchanged upon LTP induction, whereas the GluA2/GluA3 AMPARs are activated by cAMP signaling, enhancing their channel conductance and thereby increasing the current generated in potentiated synapses. This model describes for the first time a form of GluA3-dependent LTP.

Error bars indicate SEM; indicates p < 0.05.