TBS of Hippocampal Inputs Gates LTP of LA-BA Synapses
(A) Schematic of the experimental configuration: optical stimulation of vCA1 axons in the BA was paired with electrical stimulation of the LA while recording from PNs.
(B) Representative traces (average of ten sweeps) showing EPSPs evoked by electrical stimulation of the LA before and after TBS (50 trains). TBS was applied to the LA only (top), to the LA 10 ms after optical TBS of vCA1 axons without (upper middle) or with CGP54626 (5 μM, lower middle), or to the LA 100 ms after optical TBS of vCA1 axons (bottom). Stimulation artifacts are truncated.
(C) The EPSP amplitude plotted over time (stimulation occurs every 10 s). Dashed rectangles represent intervals used for statistical comparisons in (D). Pairing of LA-vCA1 TBS (n = 7) induced LTP, which did not occur with TBS of the LA only (n = 6), but also in the presence of CGP54626 (n = 5) or when TBS of the LA was evoked 100 ms after TBS of the vCA1 axons (n = 7).
(D) Quantification of the intervals in (C). Each condition is compared with its own baseline. The EPSP amplitude was significantly increased (∗p < 0.05) after LA-vCA1 pairing with 10-ms delay.
(E and F) Schematic model of the vCA1-BA circuit.
(E) During sparse firing of vCA1 pyramidal neurons projecting to the BA, vCA1 input to BA INs drives FFI onto BA PNs. This results in brief vCA1-mediated excitation and hyperpolarization of PNs via GABAB receptors. Theta frequency stimulation of the LA alone does not elicit LTP.
(F) During theta frequency inputs driven by vCA1 pyramidal cells to BA neurons, a GABAB-receptor-dependent depression of GABA release from INs occurs. This results in broadening of the temporal window for the integration of excitation in PNs. This mechanism allows the induction of heterosynaptic LTP at LA-BA synapses when LA is simultaneously stimulated at theta frequency. Colored triangles depict presynaptic terminals, and their size indicates synaptic strength. Data are presented as means ± SEM.