Fig. 5.

D1R and D2R coactivation drives t-LTP induction at extended timing window under intact GABAergic inhibition. (A) Absence of t-LTP induction in normal bath. (B) t-LTP induced in the presence of dopamine during EPSP-AP pairings. (Scale bars: 2 mV, 25 ms.) (C) Dopamine enabled t-LTP at an Δt of 30 ms was blocked by either SCH23390 or haloperidol. (D) Both SKF81297 and quinpirole, but not either alone, were needed to enable t-LTP. Δt was 30 ms for experiments in A–D. (E) Summary of dopamine effects on t-LTP at various timing intervals. Some data presented are replotted for direct comparisons. (F) Working hypothesis: under native conditions, layer V PFC neurons are under powerful constraint by local GABAergic interneurons, as no t-LTP can be induced by our induction protocol (Left). At the 10-ms timing interval, activation of presynaptic D2Rs on local interneurons alone is sufficient to gate t-LTP, presumably by suppressing GABAergic inhibition (Center). At the 30-ms interval, coactivation of both D1Rs and D2Rs in different microcircuits is necessary to permit t-LTP, mediated by concurrent D2R suppression of GABAergic inhibition and postsynaptic D1R-activated cAMP-PKA signaling (Right).