5-HT 1A and 5-HT 7 receptors differently modulate AMPA receptor-mediated hippocampal synaptic transmission

L. Costa, C. Trovato, S. A. Musumeci, M. V. Catania, L. Ciranna

Research output: Contribution to journalArticlepeer-review

Abstract

We have studied the effects of 5-HT 1A and 5-HT 7 serotonin receptor activation in hippocampal CA3-CA1 synaptic transmission using patch clamp on mouse brain slices. Application of either 5-HT or 8-OH DPAT, a mixed 5-HT 1A/5-HT 7 receptor agonist, inhibited AMPA receptor-mediated excitatory post synaptic currents (EPSCs); this effect was mimicked by the 5-HT 1A receptor agonist 8-OH PIPAT and blocked by the 5-HT 1A antagonist NAN-190. 8-OH DPAT increased paired-pulse facilitation and reduced the frequency of mEPSCs, indicating a presynaptic reduction of glutamate release probability. In another group of neurons, 8-OH DPAT enhanced EPSC amplitude but did not alter paired-pulse facilitation, suggesting a postsynaptic action; this effect persisted in the presence of NAN-190 and was blocked by the 5-HT 7 receptor antagonist SB-269970. To confirm that EPSC enhancement was mediated by 5-HT 7 receptors, we used the compound LP-44, which is considered a selective 5-HT 7 agonist. However, LP-44 reduced EPSC amplitude in most cells and instead increased EPSC amplitude in a subset of neurons, similarly to 8-OH DPAT. These effects were respectively antagonized by NAN-190 and by SB-269970, indicating that under our experimental condition LP-44 behaved as a mixed agonist. 8-OH DPAT also modulated the current evoked by exogenously applied AMPA, inducing either a reduction or an increase of amplitude in distinct neurons; these effects were respectively blocked by 5-HT 1A and 5-HT 7 receptor antagonists, indicating that both receptors exert a postsynaptic action. Our results show that 5-HT 1A receptors inhibit CA3-CA1 synaptic transmission acting both pre- and postsynaptically, whereas 5-HT 7 receptors enhance CA3-CA1 synaptic transmission acting exclusively at a postsynaptic site. We suggest that a selective pharmacological targeting of either subtype may be envisaged in pathological loss of hippocampal-dependent cognitive functions. In this respect, we underline the need for new selective agonists of 5-HT 7 receptors.

Original languageEnglish
Pages (from-to)790-801
Number of pages12
JournalHippocampus
Volume22
Issue number4
DOIs
Publication statusPublished - Apr 2012

Keywords

  • 5-HT
  • 5-HT
  • AMPA
  • Electrophysiology
  • Patch clamp

ASJC Scopus subject areas

  • Cognitive Neuroscience

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