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5-HT4 receptor activation induces long-lasting EPSP-spike potentiation in CA1 pyramidal neurons
Article first published online: 14 AUG 2006
DOI: 10.1111/j.1460-9568.2006.04949.x
Additional Information
How to Cite
Mlinar, B., Mascalchi, S., Mannaioni, G., Morini, R. and Corradetti, R. (2006), 5-HT4 receptor activation induces long-lasting EPSP-spike potentiation in CA1 pyramidal neurons. European Journal of Neuroscience, 24: 719–731. doi: 10.1111/j.1460-9568.2006.04949.x
Publication History
- Issue published online: 14 AUG 2006
- Article first published online: 14 AUG 2006
- Received 10 January 2006, revised 2 May 2006, accepted 18 May 2006
- Abstract
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Keywords:
- inward rectifier;
- hippocampus;
- rat;
- serotonin
Abstract
Recent studies implicated involvement of the 5-hydroxytryptamine4 (5-HT4) receptor in cognitive and emotional processes. The highest 5-HT4 receptor densities in the brain are found in the limbic system including the hippocampus. Here we used the selective 5-HT4 receptor full agonist, N-pentyl-N′-aminoguanidine carbazimidamide (SDZ-216454) to characterize effects of 5-HT4 receptor activation in whole-cell and field recordings in the area CA1 in hippocampal slices prepared from 3 to 4- and 6 to 9-week-old rats, respectively. Extracellular recordings showed that transient 5-HT4 receptor activation by 10–20 min application of SDZ-216454 induces field excitatory postsynaptic potential (fEPSP)-population spike potentiation (ESP5-HT4), which persisted for as long as we held the recordings (> 2 h). ESP5-HT4 displayed characteristics different from EPSP-spike potentiation that accompanies long-term potentiation; it developed without an associated increase in synaptic transmission, was independent on afferent input, activity of postsynaptic neurons and N-methyl-d-aspartate receptor activation; and was expressed in the presence of GABA receptor antagonists. ESP5-HT4 was also induced by transient application of the natural neurotransmitter, 5-HT. The increase in the evoked population spike (PS) induced by SDZ-216454 was not prevented by blockers of hyperpolarization-activated cation current (Ih), Cs+ and ZD-7288, but was mimicked and occluded by 150 µm Ba2+. Whole-cell voltage-clamp recordings from pyramidal neurons demonstrated that SDZ-216454 application increases membrane resistance with a concomitant decrease in a Ba2+-sensitive inwardly rectifying K+ current and the Ba2+-insensitive K+ current underlying slow afterhyperpolarization (IsAHP). We conclude that 5-HT4 receptor activation may cause a long-lasting excitability increase in CA1 pyramidal neurons by inhibition of a Ba2+-sensitive inwardly rectifying K+ current.