Distal dendritic inputs control neuronal activity by heterosynaptic potentiation of proximal inputs

Edward B. Han, Stephen F. Heinemann

Research output: Contribution to journalArticle

27 Scopus citations


Synapses onto distal dendritic tufts are believed to function by modulating time-locked proximal inputs; however, the role of these synapses when proximal inputs are asynchronous or silent is unknown. Surprisingly, we found that activation of apical tuft synapses alone resulted in heterosynaptic potentiation of proximal synapses. InmouseadulthippocampalCA1pyramidal neurons,weshowthat activation of distal inputs from the entorhinal cortex (EC) specifically strengthens proximal synapses projecting from CA3. This slowAMPAreceptor-mediated potentiation is accompanied by increased synaptic GluN2B-containing NMDA receptors, which are normally restricted to juvenile animals. These two synaptic modifications interact to generate striking bidirectional metaplastic changes. Heterosynaptically potentiated synapses become resistant to subsequent long-term potentiation (LTP) as the two forms ofAMPAreceptor-mediated potentiation occlude. However, this is only true whentheLTPinduction protocol is relativelyweak.Whenit is strongandrepeated, themagnitudeofLTPafter heterosynaptic plasticity is greatly increased, specifically through the activation of GluN2B-containing NMDA receptors. Thus, CA1 neurons expressing heterosynaptic potentiation induced by external sensory input from the EC become more strongly driven by internally generated environmental representations from CA3. Furthermore, subsequent SC LTP in this ensemble is shifted to potentiate only strongly activated CA3 inputs, while endowing these synapses with enhanced potentiation. These results show that one set of inputs can exert long-lasting heterosynaptic control over another, allowing the coupling of two functionally and spatially distinct pathways, thereby greatly expanding the repertoire of cellular and network plasticity.

Original languageEnglish
Pages (from-to)1314-1325
Number of pages12
JournalJournal of Neuroscience
Issue number4
StatePublished - Jan 23 2013
Externally publishedYes

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