Neurotensin enhances GABAergic activity in rat hippocampus CA1 region by modulating L-type calcium channels

Shanshan Li, Jonathan D. Geiger, Saobo Lei

Research output: Contribution to journalArticlepeer-review

15 Scopus citations


Neurotensin (NT) is a tridecapeptide that interacts with three NT receptors; NTS1, NTS2, and NTS3. Although NT has been reported to modulate GABAergic activity in the brain, the underlying cellular and molecular mechanisms of NT are elusive. Here, we examined the effects of NT on GABAergic transmission and the involved cellular and signaling mechanisms of NT in the hippocampus. Application of NT dose-dependently increased the frequency of spontaneous inhibitory postsynaptic currents (sIPSCs) recorded from CA1 pyramidal neurons with no effects on the amplitude of sIPSCs. NT did not change either the frequency or the amplitude of miniature (m)IPSCs recorded in the presence of tetrodotoxin. Triple immunofluorescent staining of recorded interneurons demonstrated the expression of NTS1 on GABAergic interneurons. NT increased the action potential firing rate but decreased the afterhyperpolarization (AHP) amplitude in identified CA1 interneurons. Application of L-type calcium channel blockers (nimodipine and nifedipine) abolished NT-induced increases in action potential firing rate and sIPSC frequency and reduction in AHP amplitude, suggesting that the effects of NT are mediated by interaction with L-type Ca2+ channels. NT-induced increase in sIPSC frequency was blocked by application of the specific NTS1 antagonist SR48692, the phospholipase C (PLC) inhibitor U73122, the IP 3 receptor antagonist 2-APB, and the protein kinase C inhibitor GF109203X, suggesting that NT increases γ-aminobutyric acid release via a PLC pathway. Our results provide a cellular mechanism by which NT controls GABAergic neuronal activity in hippocampus.

Original languageEnglish (US)
Pages (from-to)2134-2143
Number of pages10
JournalJournal of Neurophysiology
Issue number5
StatePublished - May 2008
Externally publishedYes

ASJC Scopus subject areas

  • Neuroscience(all)
  • Physiology

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