Coactivation of Pre- and Postsynaptic Signaling Mechanisms Determines Cell-Specific Spike-Timing-Dependent Plasticity

Thanos Tzounopoulos, Maria E. Rubio, John E. Keen, Laurence O. Trussell

Research output: Contribution to journalArticlepeer-review

171 Scopus citations


Synapses may undergo long-term increases or decreases in synaptic strength dependent on critical differences in the timing between pre-and postsynaptic activity. Such spike-timing-dependent plasticity (STDP) follows rules that govern how patterns of neural activity induce changes in synaptic strength. Synaptic plasticity in the dorsal cochlear nucleus (DCN) follows Hebbian and anti-Hebbian patterns in a cell-specific manner. Here we show that these opposing responses to synaptic activity result from differential expression of two signaling pathways. Ca2+/calmodulin-dependent protein kinase II (CaMKII) signaling underlies Hebbian postsynaptic LTP in principal cells. By contrast, in interneurons, a temporally precise anti-Hebbian synaptic spike-timing rule results from the combined effects of postsynaptic CaMKII-dependent LTP and endocannabinoid-dependent presynaptic LTD. Cell specificity in the circuit arises from selective targeting of presynaptic CB1 receptors in different axonal terminals. Hence, pre- and postsynaptic sites of expression determine both the sign and timing requirements of long-term plasticity in interneurons.

Original languageEnglish (US)
Pages (from-to)291-301
Number of pages11
Issue number2
StatePublished - Apr 19 2007



ASJC Scopus subject areas

  • Neuroscience(all)


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