Gain in sensitivity and loss in temporal contrast of STDP by dopaminergic modulation at hippocampal synapses.
Spike-timing-dependent plasticity (STDP) is considered a physiologically relevant form of Hebbian learning. However, behavioral learning often involves action of reinforcement or reward signals such as dopamine. Here, we examined how dopamine influences the quantitative rule of STDP at glutamatergic synapses of hippocampal neurons. The presence of 20 muM dopamine during paired pre- and postsynaptic spiking activity expanded the effective time window for timing-dependent long-term potentiation (t-LTP) to at least -45 ms, and allowed normally ineffective weak stimuli with fewer spike pairs to induce significant t-LTP. Meanwhile, dopamine did not affect the degree of t-LTP induced by normal strong stimuli with spike timing (ST) of +10 ms. Such dopamine-dependent enhancement in the sensitivity of t-LTP was completely blocked by the D1-like dopamine receptor antagonist SCH23390, but not by the D2-like dopamine receptor antagonist sulpiride. Surprisingly, timing-dependent long-term depression (t-LTD) at negative ST was converted into t-LTP by dopamine treatment; this conversion was also blocked by SCH23390. In addition, t-LTP in the presence of dopamine was completely blocked by the NMDA receptor antagonist 2-amino-5-phosphonovaleric acid, indicating that D1-like receptor-mediated modulation appears to act through the classical NMDA receptor-mediated signaling pathway that underlies STDP. These results provide a quantitative and mechanistic basis for a previously undescribed learning rule that depends on pre- and postsynaptic ST, as well as the global reward signal.
Zhang
Ji-Chuan
JC
Department of Neurobiology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261, USA.
Lau
Pak-Ming
PM
Bi
Guo-Qiang
GQ
D000818:Animals; D002118:Calcium / Q000378:metabolism; D002478:Cells, Cultured; D004298:Dopamine / Q000494:pharmacology*; D006624:Hippocampus / Q000187:drug effects* / Q000502:physiology; D017774:Long-Term Potentiation / Q000187:drug effects; D009473:Neuronal Plasticity / Q000187:drug effects* / Q000502:physiology; D051381:Rats; D017447:Receptors, Dopamine D1 / Q000502:physiology; D017448:Receptors, Dopamine D2 / Q000502:physiology; D016194:Receptors, N-Methyl-D-Aspartate / Q000502:physiology; D013569:Synapses / Q000187:drug effects* / Q000502:physiology
D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; D016194:Receptors, N-Methyl-D-Aspartate; D002118:Calcium; D004298:Dopamine