TY - JOUR
T1 - PKM-ζ is not required for hippocampal synaptic plasticity, learning and memory
AU - Volk, Lenora J.
AU - Bachman, Julia L.
AU - Johnson, Richard
AU - Yu, Yilin
AU - Huganir, Richard L.
N1 - Funding Information:
AcknowledgementsWethankG.SchützforprovidingtheCaMKIICre-ERT2mice, M. Gallagher and D. Smith for advice on behaviour andM. Coulter for technicalsupport. Wealso thank all members ofthe Huganirlabfor discussionand support. Thiswork was supported by grants from the National Institute of Health (NS36715) and the Howard Hughes Medical Institute (to R.L.H.). L.J.V. is supported by a training grant from the National Institute of Health (T32MH15330).
PY - 2013/1/17
Y1 - 2013/1/17
N2 - Long-term potentiation (LTP), a well-characterized form of synaptic plasticity, has long been postulated as a cellular correlate of learning and memory. Although LTP can persist for long periods of time, the mechanisms underlying LTP maintenance, in the midst of ongoing protein turnover and synaptic activity, remain elusive. Sustained activation of the brain-specific protein kinase C (PKC) isoform protein kinase M-ζ (PKM-ζ) has been reported to be necessary for both LTP maintenance and long-term memory. Inhibiting PKM-ζ activity using a synthetic zeta inhibitory peptide (ZIP) based on the PKC-ζ pseudosubstrate sequence reverses established LTP in vitro and in vivo. More notably, infusion of ZIP eliminates memories for a growing list of experience-dependent behaviours, including active place avoidance, conditioned taste aversion, fear conditioning and spatial learning. However, most of the evidence supporting a role for PKM-ζ in LTP and memory relies heavily on pharmacological inhibition of PKM-ζ by ZIP. To further investigate the involvement of PKM-ζ in the maintenance of LTP and memory, we generated transgenic mice lacking PKC-ζ and PKM-ζ. We find that both conventional and conditional PKC-ζ/PKM-ζ knockout mice show normal synaptic transmission and LTP at Schaffer collateral-CA1 synapses, and have no deficits in several hippocampal-dependent learning and memory tasks. Notably, ZIP still reverses LTP in PKC-ζ/PKM-ζ knockout mice, indicating that the effects of ZIP are independent of PKM-ζ.
AB - Long-term potentiation (LTP), a well-characterized form of synaptic plasticity, has long been postulated as a cellular correlate of learning and memory. Although LTP can persist for long periods of time, the mechanisms underlying LTP maintenance, in the midst of ongoing protein turnover and synaptic activity, remain elusive. Sustained activation of the brain-specific protein kinase C (PKC) isoform protein kinase M-ζ (PKM-ζ) has been reported to be necessary for both LTP maintenance and long-term memory. Inhibiting PKM-ζ activity using a synthetic zeta inhibitory peptide (ZIP) based on the PKC-ζ pseudosubstrate sequence reverses established LTP in vitro and in vivo. More notably, infusion of ZIP eliminates memories for a growing list of experience-dependent behaviours, including active place avoidance, conditioned taste aversion, fear conditioning and spatial learning. However, most of the evidence supporting a role for PKM-ζ in LTP and memory relies heavily on pharmacological inhibition of PKM-ζ by ZIP. To further investigate the involvement of PKM-ζ in the maintenance of LTP and memory, we generated transgenic mice lacking PKC-ζ and PKM-ζ. We find that both conventional and conditional PKC-ζ/PKM-ζ knockout mice show normal synaptic transmission and LTP at Schaffer collateral-CA1 synapses, and have no deficits in several hippocampal-dependent learning and memory tasks. Notably, ZIP still reverses LTP in PKC-ζ/PKM-ζ knockout mice, indicating that the effects of ZIP are independent of PKM-ζ.
UR - http://www.scopus.com/inward/record.url?scp=84872611798&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84872611798&partnerID=8YFLogxK
U2 - 10.1038/nature11802
DO - 10.1038/nature11802
M3 - Article
C2 - 23283174
AN - SCOPUS:84872611798
SN - 0028-0836
VL - 493
SP - 420
EP - 423
JO - Nature
JF - Nature
IS - 7432
ER -