TY - JOUR
T1 - Norepinephrine enhances a discrete form of long-term depression during fear memory storage
AU - Clem, Roger L.
AU - Huganir, Richard L.
PY - 2013
Y1 - 2013
N2 - Amygdala excitatory synaptic strengthening is thought to contribute to both conditioned fear and anxiety. Thus, one basis for behavioral flexibility could allow these pathways to be weakened and corresponding emotion to be attenuated. However, synaptic depression within the context of amygdala-dependent behavior remains poorly understood. Previous work identified lateral amygdala (LA) calciumpermeable AMPA receptors (CP-AMPARs) as a key target for synaptic removal in long-term depression (LTD) and persistent fear attenuation. Here we demonstrate that LA neurons express two equally potent forms of LTD with contrasting requirements for protein kinase and phosphatase activity and differential impact on CP-AMPAR trafficking. Selective removal of CP-AMPARs from synapses is contingent on group 1 metabotropic glutamate receptor (mGluR1) and PKC signaling, in contrast to an alternate LTD pathway that nonselectively removes AMPARs and requires calcineurin (PP2b). Intriguingly, the balance between these forms of LTD is shifted by posttraining activation of β-adrenergic receptors in fear conditioned mice, resulting in selective augmentation of mGluR-dependent depression. These results highlight the complexity of core mechanisms inLTDand suggest that norepinephrine exposure mediates a form of synaptic metaplasticity that recalibrates fear memory processing.
AB - Amygdala excitatory synaptic strengthening is thought to contribute to both conditioned fear and anxiety. Thus, one basis for behavioral flexibility could allow these pathways to be weakened and corresponding emotion to be attenuated. However, synaptic depression within the context of amygdala-dependent behavior remains poorly understood. Previous work identified lateral amygdala (LA) calciumpermeable AMPA receptors (CP-AMPARs) as a key target for synaptic removal in long-term depression (LTD) and persistent fear attenuation. Here we demonstrate that LA neurons express two equally potent forms of LTD with contrasting requirements for protein kinase and phosphatase activity and differential impact on CP-AMPAR trafficking. Selective removal of CP-AMPARs from synapses is contingent on group 1 metabotropic glutamate receptor (mGluR1) and PKC signaling, in contrast to an alternate LTD pathway that nonselectively removes AMPARs and requires calcineurin (PP2b). Intriguingly, the balance between these forms of LTD is shifted by posttraining activation of β-adrenergic receptors in fear conditioned mice, resulting in selective augmentation of mGluR-dependent depression. These results highlight the complexity of core mechanisms inLTDand suggest that norepinephrine exposure mediates a form of synaptic metaplasticity that recalibrates fear memory processing.
UR - http://www.scopus.com/inward/record.url?scp=84880443839&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84880443839&partnerID=8YFLogxK
U2 - 10.1523/JNEUROSCI.3317-12.2013
DO - 10.1523/JNEUROSCI.3317-12.2013
M3 - Article
C2 - 23864672
AN - SCOPUS:84880443839
SN - 0270-6474
VL - 33
SP - 11825
EP - 11832
JO - Journal of Neuroscience
JF - Journal of Neuroscience
IS - 29
ER -