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5-HT4 receptor activation induces long-lasting EPSP-spike potentiation in CA1 pyramidal neurons.
Eur J Neurosci. 2006 Aug; 24(3):719-31.EJ

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 (ESP(5-HT4)), which persisted for as long as we held the recordings (> 2 h). ESP(5-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. ESP(5-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 microm 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 (I(sAHP)). 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.

Authors+Show Affiliations

Department of Preclinical and Clinical Pharmacology Mario Aiazzi-Mancini University of Florence, Viale G. Pieraccini 6, 50139 Florence, Italy. bmlinar@unifi.itNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

16930402

Citation

Mlinar, Boris, et al. "5-HT4 Receptor Activation Induces Long-lasting EPSP-spike Potentiation in CA1 Pyramidal Neurons." The European Journal of Neuroscience, vol. 24, no. 3, 2006, pp. 719-31.
Mlinar B, Mascalchi S, Mannaioni G, et al. 5-HT4 receptor activation induces long-lasting EPSP-spike potentiation in CA1 pyramidal neurons. Eur J Neurosci. 2006;24(3):719-31.
Mlinar, B., Mascalchi, S., Mannaioni, G., Morini, R., & Corradetti, R. (2006). 5-HT4 receptor activation induces long-lasting EPSP-spike potentiation in CA1 pyramidal neurons. The European Journal of Neuroscience, 24(3), 719-31.
Mlinar B, et al. 5-HT4 Receptor Activation Induces Long-lasting EPSP-spike Potentiation in CA1 Pyramidal Neurons. Eur J Neurosci. 2006;24(3):719-31. PubMed PMID: 16930402.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - 5-HT4 receptor activation induces long-lasting EPSP-spike potentiation in CA1 pyramidal neurons. AU - Mlinar,Boris, AU - Mascalchi,Simona, AU - Mannaioni,Guido, AU - Morini,Raffaella, AU - Corradetti,Renato, PY - 2006/8/26/pubmed PY - 2006/11/2/medline PY - 2006/8/26/entrez SP - 719 EP - 31 JF - The European journal of neuroscience JO - Eur J Neurosci VL - 24 IS - 3 N2 - 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 (ESP(5-HT4)), which persisted for as long as we held the recordings (> 2 h). ESP(5-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. ESP(5-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 microm 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 (I(sAHP)). 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. SN - 0953-816X UR - https://www.unboundmedicine.com/medline/citation/16930402/5_HT4_receptor_activation_induces_long_lasting_EPSP_spike_potentiation_in_CA1_pyramidal_neurons_ L2 - https://doi.org/10.1111/j.1460-9568.2006.04949.x DB - PRIME DP - Unbound Medicine ER -