Activity-dependent upregulation of presynaptic kainate receptors at immature CA3-CA1 synapses

Vernon R.J. Clarke, Svetlana M. Molchanova, Teemu Hirvonen, Tomi Taira, Sari E. Lauri*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

10 Scopus citations


Presynaptic kainate-type glutamate receptors (KARs) regulate glutamate release probability and short-term plasticity in various areas of the brain. Here we show that long-term depression (LTD) in the area CA1 of neonatal rodent hippocampus is associated with an upregulation of tonic inhibitory KAR activity, which contributes to synaptic depression and causes a pronounced increase in short-term facilitation of transmission. This increased KAR function was mediated by high-affinity receptors and required activation of NMDA receptors, nitric oxide (NO) synthetase, and postsynaptic calcium signaling. In contrast, KAR activity was irreversibly downregulated in response to induction of long-term potentiation in a manner that depended on activation of the TrkB-receptor of BDNF. Both tonic KAR activity and its plasticity were restricted to early stages of synapse development and were lost in parallel with maturation of the network due to ongoing BDNF-TrkB signaling. These data show that presynaptic KARs are targets for activity-dependent modulation via diffusible messengers NO and BDNF, which enhance and depress tonic KAR activity at immature synapses, respectively. The plasticity of presynaptic KARs in the developing network allows nascent synapses to shape their response to incoming activity. In particular, upregulation of KAR function after LTD allows the synapse to preferentially pass high-frequency afferent activity. This can provide a potential rescue from synapse elimination by uncorrelated activity and also increase the computational dynamics of the developing CA3-CA1 circuitry.

Original languageEnglish (US)
Pages (from-to)16902-16916
Number of pages15
JournalJournal of Neuroscience
Issue number50
StatePublished - Dec 10 2014


  • GluK1
  • LTD
  • Short-term plasticity
  • Synapse maturation

ASJC Scopus subject areas

  • Neuroscience(all)


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