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

• Published in: Hippocampus 2012-04, Vol.22 (4), p.790-801
• Main Authors: Costa, L., Trovato, C., Musumeci, S.A., Catania, M.V., Ciranna, L.
• Format: Article
• Language: English
• ISSN: 1050-9631; 1098-1063
• DOI: 10.1002/hipo.20940

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. © 2011 Wiley Periodicals, Inc.