cAMP/PKA signaling and RIM1α mediate presynaptic LTP in the lateral amygdala
Proceedings of the National Academy of Sciences. 2008-09-24; 105(39): 15130-15135
DOI: 10.1073/pnas.0806938105
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1. Proc Natl Acad Sci U S A. 2008 Sep 30;105(39):15130-5. doi:
10.1073/pnas.0806938105. Epub 2008 Sep 24.
cAMP/PKA signaling and RIM1alpha mediate presynaptic LTP in the lateral amygdala.
Fourcaudot E(1), Gambino F, Humeau Y, Casassus G, Shaban H, Poulain B, Lüthi A.
Author information:
(1)Friedrich Miescher Institute for Biomedical Research, CH-4058 Basel,
Switzerland.
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 RIM1alpha
(RIM1alpha(-/-)), we demonstrate that RIM1alpha is required for both chemically
and synaptically induced presynaptic LTP. Further analysis of cortico-LA synaptic
transmission in RIM1alpha(-/-) mice revealed a deficit in Ca(2+)-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 RIM1alpha-dependent LTP may involve changes in Ca(2+)-release
coupling.
DOI: 10.1073/pnas.0806938105
PMCID: PMC2567504
PMID: 18815362 [Indexed for MEDLINE]