cAMP/PKA signaling and RIM1α mediate presynaptic LTP in the lateral amygdala

Elodie Fourcaudot, Frédéric Gambino, Yann Humeau, Guillaume Casassus, Hamdy Shaban, Bernard Poulain, Andreas Lüthi

Research output: Contribution to journalArticle

69 Citations (Scopus)

Abstract

NMDA receptor-dependent long-term potentiation (LTP) of glutamatergic synaptic transmission in sensory pathways from auditory thalamus or cortex to the lateral amygdala (LA) underlies the acquisition of auditory fear conditioning. Whereas the mechanisms of postsynaptic LTP at thalamo-LA synapses are well understood, much less is known about the sequence of events mediating presynaptic NMDA receptor-dependent LTP at cortico-LA synapses. Here, we show that presynaptic cortico-LA LTP can be entirely accounted for by a persistent increase in the vesicular release probability. At the molecular level, we found that signaling via the cAMP/PKA pathway is necessary and sufficient for LTP induction. Moreover, by using mice lacking the active-zone protein and PKA target RIM1α (RIM1α-/-), we demonstrate that RIM1α is required for both chemically and synaptically induced presynaptic LTP. Further analysis of cortico-LA synaptic transmission in RIM1α-/- mice revealed a deficit in Ca2+-release coupling leading to a lower baseline release probability. Our results reveal the molecular mechanisms underlying the induction of presynaptic LTP at cortico-LA synapses and indicate that RIM1α-dependent LTP may involve changes in Ca2+-release coupling.

Original languageEnglish
Pages (from-to)15130-15135
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume105
Issue number39
DOIs
Publication statusPublished - Sep 30 2008
Externally publishedYes

Fingerprint

Long-Term Potentiation
Amygdala
Synapses
N-Methyl-D-Aspartate Receptors
Synaptic Transmission
Auditory Pathways
Presynaptic Receptors
Thalamus
Fear

Keywords

  • Fear conditioning
  • Release probability
  • Synaptic plasticity
  • Synaptic transmission

ASJC Scopus subject areas

  • General

Cite this

cAMP/PKA signaling and RIM1α mediate presynaptic LTP in the lateral amygdala. / Fourcaudot, Elodie; Gambino, Frédéric; Humeau, Yann; Casassus, Guillaume; Shaban, Hamdy; Poulain, Bernard; Lüthi, Andreas.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 105, No. 39, 30.09.2008, p. 15130-15135.

Research output: Contribution to journalArticle

Fourcaudot, E, Gambino, F, Humeau, Y, Casassus, G, Shaban, H, Poulain, B & Lüthi, A 2008, 'cAMP/PKA signaling and RIM1α mediate presynaptic LTP in the lateral amygdala', Proceedings of the National Academy of Sciences of the United States of America, vol. 105, no. 39, pp. 15130-15135. https://doi.org/10.1073/pnas.0806938105
Fourcaudot, Elodie ; Gambino, Frédéric ; Humeau, Yann ; Casassus, Guillaume ; Shaban, Hamdy ; Poulain, Bernard ; Lüthi, Andreas. / cAMP/PKA signaling and RIM1α mediate presynaptic LTP in the lateral amygdala. In: Proceedings of the National Academy of Sciences of the United States of America. 2008 ; Vol. 105, No. 39. pp. 15130-15135.
@article{f85c207d9f624f7594b145d2e1547679,
title = "cAMP/PKA signaling and RIM1α mediate presynaptic LTP in the lateral amygdala",
abstract = "NMDA receptor-dependent long-term potentiation (LTP) of glutamatergic synaptic transmission in sensory pathways from auditory thalamus or cortex to the lateral amygdala (LA) underlies the acquisition of auditory fear conditioning. Whereas the mechanisms of postsynaptic LTP at thalamo-LA synapses are well understood, much less is known about the sequence of events mediating presynaptic NMDA receptor-dependent LTP at cortico-LA synapses. Here, we show that presynaptic cortico-LA LTP can be entirely accounted for by a persistent increase in the vesicular release probability. At the molecular level, we found that signaling via the cAMP/PKA pathway is necessary and sufficient for LTP induction. Moreover, by using mice lacking the active-zone protein and PKA target RIM1α (RIM1α-/-), we demonstrate that RIM1α is required for both chemically and synaptically induced presynaptic LTP. Further analysis of cortico-LA synaptic transmission in RIM1α-/- mice revealed a deficit in Ca2+-release coupling leading to a lower baseline release probability. Our results reveal the molecular mechanisms underlying the induction of presynaptic LTP at cortico-LA synapses and indicate that RIM1α-dependent LTP may involve changes in Ca2+-release coupling.",
keywords = "Fear conditioning, Release probability, Synaptic plasticity, Synaptic transmission",
author = "Elodie Fourcaudot and Fr{\'e}d{\'e}ric Gambino and Yann Humeau and Guillaume Casassus and Hamdy Shaban and Bernard Poulain and Andreas L{\"u}thi",
year = "2008",
month = "9",
day = "30",
doi = "10.1073/pnas.0806938105",
language = "English",
volume = "105",
pages = "15130--15135",
journal = "Proceedings of the National Academy of Sciences of the United States of America",
issn = "0027-8424",
number = "39",

}

TY - JOUR

T1 - cAMP/PKA signaling and RIM1α mediate presynaptic LTP in the lateral amygdala

AU - Fourcaudot, Elodie

AU - Gambino, Frédéric

AU - Humeau, Yann

AU - Casassus, Guillaume

AU - Shaban, Hamdy

AU - Poulain, Bernard

AU - Lüthi, Andreas

PY - 2008/9/30

Y1 - 2008/9/30

N2 - NMDA receptor-dependent long-term potentiation (LTP) of glutamatergic synaptic transmission in sensory pathways from auditory thalamus or cortex to the lateral amygdala (LA) underlies the acquisition of auditory fear conditioning. Whereas the mechanisms of postsynaptic LTP at thalamo-LA synapses are well understood, much less is known about the sequence of events mediating presynaptic NMDA receptor-dependent LTP at cortico-LA synapses. Here, we show that presynaptic cortico-LA LTP can be entirely accounted for by a persistent increase in the vesicular release probability. At the molecular level, we found that signaling via the cAMP/PKA pathway is necessary and sufficient for LTP induction. Moreover, by using mice lacking the active-zone protein and PKA target RIM1α (RIM1α-/-), we demonstrate that RIM1α is required for both chemically and synaptically induced presynaptic LTP. Further analysis of cortico-LA synaptic transmission in RIM1α-/- mice revealed a deficit in Ca2+-release coupling leading to a lower baseline release probability. Our results reveal the molecular mechanisms underlying the induction of presynaptic LTP at cortico-LA synapses and indicate that RIM1α-dependent LTP may involve changes in Ca2+-release coupling.

AB - NMDA receptor-dependent long-term potentiation (LTP) of glutamatergic synaptic transmission in sensory pathways from auditory thalamus or cortex to the lateral amygdala (LA) underlies the acquisition of auditory fear conditioning. Whereas the mechanisms of postsynaptic LTP at thalamo-LA synapses are well understood, much less is known about the sequence of events mediating presynaptic NMDA receptor-dependent LTP at cortico-LA synapses. Here, we show that presynaptic cortico-LA LTP can be entirely accounted for by a persistent increase in the vesicular release probability. At the molecular level, we found that signaling via the cAMP/PKA pathway is necessary and sufficient for LTP induction. Moreover, by using mice lacking the active-zone protein and PKA target RIM1α (RIM1α-/-), we demonstrate that RIM1α is required for both chemically and synaptically induced presynaptic LTP. Further analysis of cortico-LA synaptic transmission in RIM1α-/- mice revealed a deficit in Ca2+-release coupling leading to a lower baseline release probability. Our results reveal the molecular mechanisms underlying the induction of presynaptic LTP at cortico-LA synapses and indicate that RIM1α-dependent LTP may involve changes in Ca2+-release coupling.

KW - Fear conditioning

KW - Release probability

KW - Synaptic plasticity

KW - Synaptic transmission

UR - http://www.scopus.com/inward/record.url?scp=54449092370&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=54449092370&partnerID=8YFLogxK

U2 - 10.1073/pnas.0806938105

DO - 10.1073/pnas.0806938105

M3 - Article

VL - 105

SP - 15130

EP - 15135

JO - Proceedings of the National Academy of Sciences of the United States of America

JF - Proceedings of the National Academy of Sciences of the United States of America

SN - 0027-8424

IS - 39

ER -