Neuromodulators Control the Polarity of Spike-Timing-Dependent Synaptic Plasticity

Geun Hee Seol, Jokubas Ziburkus, Shi Yong Huang, Lihua Song, In Tae Kim, Kogo Takamiya, Richard L. Huganir, Hey Kyoung Lee, Alfredo Kirkwood

Research output: Contribution to journalArticlepeer-review

320 Citations (Scopus)


Near coincidental pre- and postsynaptic action potentials induce associative long-term potentiation (LTP) or long-term depression (LTD), depending on the order of their timing. Here, we show that in visual cortex the rules of this spike-timing-dependent plasticity are not rigid, but shaped by neuromodulator receptors coupled to adenylyl cyclase (AC) and phospholipase C (PLC) signaling cascades. Activation of the AC and PLC cascades results in phosphorylation of postsynaptic glutamate receptors at sites that serve as specific "tags" for LTP and LTD. As a consequence, the outcome (i.e., whether LTP or LTD) of a given pattern of pre- and postsynaptic firing depends not only on the order of the timing, but also on the relative activation of neuromodulator receptors coupled to AC and PLC. These findings indicate that cholinergic and adrenergic neuromodulation associated with the behavioral state of the animal can control the gating and the polarity of cortical plasticity.

Original languageEnglish
Pages (from-to)919-929
Number of pages11
Issue number6
Publication statusPublished - 2007 Sept 20

Bibliographical note

Funding Information:
We thank Drs S. Hsiao and E. Quinlan for critically reviewing the manuscript and C. O'Brian and Dr. F. Lee for technical assistance. Work supported by NIH Grants RO1 EY12124 to A.K. and R01-EY014882 to H.-K.L., and the HHMI Undergraduate Research Fellowship to I.T.K.



ASJC Scopus subject areas

  • General Neuroscience


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