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Pam heterozygous mice reveal essential role for Cu in amygdalar behavioral and synaptic function
Author(s) -
Gaier Eric D.,
Eipper Betty A.,
Mains Richard E.
Publication year - 2014
Publication title -
annals of the new york academy of sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.712
H-Index - 248
eISSN - 1749-6632
pISSN - 0077-8923
DOI - 10.1111/nyas.12378
Subject(s) - long term potentiation , synaptic plasticity , neuroscience , amygdala , microbiology and biotechnology , excitatory postsynaptic potential , biology , neuropeptide , homeostasis , atp7a , chemistry , biochemistry , receptor , inhibitory postsynaptic potential , enzyme , atpase
Copper (Cu) is an essential element with many biological roles, but its roles in the mammalian nervous system are poorly understood. Mice deficient in the cuproenzyme peptidylglycine α‐amidating monooxygenase ( Pam +/− mice) were initially generated to study neuropeptide amidation. Pam +/− mice exhibit profound deficits in a few behavioral tasks, including enhancements in innate fear along with deficits in acquired fear. Interestingly, several Pam +/− phenotypes were recapitulated in Cu‐restricted wild‐type mice and rescued in Cu‐supplemented Pam +/– mice. These behaviors correspond to enhanced excitability and deficient synaptic plasticity in the amygdala of Pam +/– mice, which are also rescued by Cu supplementation. Cu and ATP7A are present at synapses, in key positions to respond to and influence synaptic activity. Further study demonstrated that extracellular Cu is necessary for wild‐type synaptic plasticity and sufficient to induce long‐term potentiation. These experiments support roles for PAM in Cu homeostasis and for synaptic Cu in amygdalar function.