Neurokinin-receptor-mediated depolarization of cortical neurons elicits an increase in glutamate release at excitatory synapses

Anne E. Stacey, Gavin L. Woodhall, Roland S.G. Jones*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review


Using whole-cell patch-clamp recordings of spontaneous synaptic activity, we have previously shown that activation of neurokinin-1 (NK1) but not NK3 receptors leads to increased GABA release onto principal cells in the rat entorhinal cortex. In the present study, we examine the effect of activation of these receptors on spontaneous excitatory synaptic responses mediated by glutamate. Both neurokinin B (NKB) and the specific NK3 receptor agonist, senktide, increased the spontaneous release of glutamate, and a similar effect was also seen with substance P (SP) and other NK1 receptor agonists. The increased release induced by either SP or senktide was absent in the presence of tetrodotoxin, demonstrating that it was likely to occur via activation of presynaptic excitatory neurons. Current-clamp recordings confirmed that principal neurons were depolarized by both NK3 and NK1 agonists. However, the response to the former but not the latter persisted in tetrodotoxin, allowing us to conclude that NK3 receptor activation provoked glutamate release via recurrent collaterals between principal neurons, whereas the NK1 receptors may be localized to excitatory interneurons. Finally, the increased release induced by senktide, but not SP, was reduced by an antagonist of group III metabotropic glutamate receptors. Thus, glutamate release from recurrent collaterals is facilitated by a presynaptic group III autoreceptor [Evans, D.I.P., Jones, R.S.G. & Woodhall, G.L. (2000) J. Neurophysiol., 83, 2519-2525], whereas the terminals of neurons responsible for the NK1-receptor induced glutamate release may not bear these receptors. These results have implications for control of activity and epileptogenesis in cortical networks.

Original languageEnglish
Pages (from-to)1896-1906
Number of pages11
JournalEuropean Journal of Neuroscience
Issue number10
Publication statusPublished - 1 Nov 2002


  • Entorhinal cortex
  • Metabotropic glutamate receptors
  • Neurokinin receptors
  • Rat


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