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 journalArticle

40 Citations (Scopus)

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

Fingerprint

8-Hydroxy-2-(di-n-propylamino)tetralin
Receptor, Serotonin, 5-HT1A
AMPA Receptors
Synaptic Transmission
Serotonin Receptors
Serotonin
Neurons
Serotonin Receptor Agonists
Serotonin Antagonists
alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid
Cognition
Glutamic Acid
Pharmacology
Brain
1-(2-methoxyphenyl)-4-(4-(2-phthalimido)butyl)piperazine

Keywords

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

ASJC Scopus subject areas

  • Cognitive Neuroscience

Cite this

5-HT 1A and 5-HT 7 receptors differently modulate AMPA receptor-mediated hippocampal synaptic transmission. / Costa, L.; Trovato, C.; Musumeci, S. A.; Catania, M. V.; Ciranna, L.

In: Hippocampus, Vol. 22, No. 4, 04.2012, p. 790-801.

Research output: Contribution to journalArticle

Costa, L. ; Trovato, C. ; Musumeci, S. A. ; Catania, M. V. ; Ciranna, L. / 5-HT 1A and 5-HT 7 receptors differently modulate AMPA receptor-mediated hippocampal synaptic transmission. In: Hippocampus. 2012 ; Vol. 22, No. 4. pp. 790-801.
@article{93af5dbb6b634cc18ac3aca8f4f0ee55,
title = "5-HT 1A and 5-HT 7 receptors differently modulate AMPA receptor-mediated hippocampal synaptic transmission",
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.",
keywords = "5-HT, 5-HT, AMPA, Electrophysiology, Patch clamp",
author = "L. Costa and C. Trovato and Musumeci, {S. A.} and Catania, {M. V.} and L. Ciranna",
year = "2012",
month = "4",
doi = "10.1002/hipo.20940",
language = "English",
volume = "22",
pages = "790--801",
journal = "Hippocampus",
issn = "1050-9631",
publisher = "Wiley-Liss Inc.",
number = "4",

}

TY - JOUR

T1 - 5-HT 1A and 5-HT 7 receptors differently modulate AMPA receptor-mediated hippocampal synaptic transmission

AU - Costa, L.

AU - Trovato, C.

AU - Musumeci, S. A.

AU - Catania, M. V.

AU - Ciranna, L.

PY - 2012/4

Y1 - 2012/4

N2 - 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.

AB - 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.

KW - 5-HT

KW - 5-HT

KW - AMPA

KW - Electrophysiology

KW - Patch clamp

UR - http://www.scopus.com/inward/record.url?scp=84858747369&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84858747369&partnerID=8YFLogxK

U2 - 10.1002/hipo.20940

DO - 10.1002/hipo.20940

M3 - Article

C2 - 21538661

AN - SCOPUS:84858747369

VL - 22

SP - 790

EP - 801

JO - Hippocampus

JF - Hippocampus

SN - 1050-9631

IS - 4

ER -