Abstract
Protein kinase M-ζ (PKM-ζ) is a constitutively active form of atypical protein kinase C that is exclusively expressed in the brain and implicated in the maintenance of long-term memory. Most studies that support a role for PKM-ζ in memory maintenance have used pharmacological PKM-ζ inhibitors such as the myristoylated zeta inhibitory peptide (ZIP) or chelerythrine. Here we use a genetic approach and target exon 9 of the Prkcz gene to generate mice that lack both protein kinase C-ζ (PKC-ζ) and PKM-ζ (Prkcz-/-mice). Prkcz-/-mice showed normal behaviour in a cage environment and in baseline tests of motor function and sensory perception, but displayed reduced anxiety-like behaviour. Notably, Prkcz-/-mice did not show deficits in learning or memory in tests of cued fear conditioning, novel object recognition, object location recognition, conditioned place preference for cocaine, or motor learning, when compared with wild-type littermates. ZIP injection into the nucleus accumbens reduced expression of cocaine-conditioned place preference in Prkcz-/-mice. In vitro, ZIP and scrambled ZIP inhibited PKM-ζ, PKC-ι and PKC-ζ with similar inhibition constant (K i) values. Chelerythrine was a weak inhibitor of PKM-ζ (K i = 76 μM). Our findings show that absence of PKM-ζ does not impair learning and memory in mice, and that ZIP can erase reward memory even when PKM-ζ is not present.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 416-419 |
| Number of pages | 4 |
| Journal | Nature |
| Volume | 493 |
| Issue number | 7432 |
| DOIs | |
| State | Published - Jan 17 2013 |
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Prkcz null mice show normal learning and memory. / Lee, Anna M.; Kanter, Benjamin R.; Wang, Dan; Lim, Jana P.; Zou, Mimi E.; Qiu, Chichen; McMahon, Thomas; Dadgar, Jahan; Fischbach-Weiss, Sarah C.; Messing, Robert O.
In: Nature, Vol. 493, No. 7432, 17.01.2013, p. 416-419.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Prkcz null mice show normal learning and memory
AU - Lee, Anna M.
AU - Kanter, Benjamin R.
AU - Wang, Dan
AU - Lim, Jana P.
AU - Zou, Mimi E.
AU - Qiu, Chichen
AU - McMahon, Thomas
AU - Dadgar, Jahan
AU - Fischbach-Weiss, Sarah C.
AU - Messing, Robert O.
PY - 2013/1/17
Y1 - 2013/1/17
N2 - Protein kinase M-ζ (PKM-ζ) is a constitutively active form of atypical protein kinase C that is exclusively expressed in the brain and implicated in the maintenance of long-term memory. Most studies that support a role for PKM-ζ in memory maintenance have used pharmacological PKM-ζ inhibitors such as the myristoylated zeta inhibitory peptide (ZIP) or chelerythrine. Here we use a genetic approach and target exon 9 of the Prkcz gene to generate mice that lack both protein kinase C-ζ (PKC-ζ) and PKM-ζ (Prkcz-/-mice). Prkcz-/-mice showed normal behaviour in a cage environment and in baseline tests of motor function and sensory perception, but displayed reduced anxiety-like behaviour. Notably, Prkcz-/-mice did not show deficits in learning or memory in tests of cued fear conditioning, novel object recognition, object location recognition, conditioned place preference for cocaine, or motor learning, when compared with wild-type littermates. ZIP injection into the nucleus accumbens reduced expression of cocaine-conditioned place preference in Prkcz-/-mice. In vitro, ZIP and scrambled ZIP inhibited PKM-ζ, PKC-ι and PKC-ζ with similar inhibition constant (K i) values. Chelerythrine was a weak inhibitor of PKM-ζ (K i = 76 μM). Our findings show that absence of PKM-ζ does not impair learning and memory in mice, and that ZIP can erase reward memory even when PKM-ζ is not present.
AB - Protein kinase M-ζ (PKM-ζ) is a constitutively active form of atypical protein kinase C that is exclusively expressed in the brain and implicated in the maintenance of long-term memory. Most studies that support a role for PKM-ζ in memory maintenance have used pharmacological PKM-ζ inhibitors such as the myristoylated zeta inhibitory peptide (ZIP) or chelerythrine. Here we use a genetic approach and target exon 9 of the Prkcz gene to generate mice that lack both protein kinase C-ζ (PKC-ζ) and PKM-ζ (Prkcz-/-mice). Prkcz-/-mice showed normal behaviour in a cage environment and in baseline tests of motor function and sensory perception, but displayed reduced anxiety-like behaviour. Notably, Prkcz-/-mice did not show deficits in learning or memory in tests of cued fear conditioning, novel object recognition, object location recognition, conditioned place preference for cocaine, or motor learning, when compared with wild-type littermates. ZIP injection into the nucleus accumbens reduced expression of cocaine-conditioned place preference in Prkcz-/-mice. In vitro, ZIP and scrambled ZIP inhibited PKM-ζ, PKC-ι and PKC-ζ with similar inhibition constant (K i) values. Chelerythrine was a weak inhibitor of PKM-ζ (K i = 76 μM). Our findings show that absence of PKM-ζ does not impair learning and memory in mice, and that ZIP can erase reward memory even when PKM-ζ is not present.
UR - http://www.scopus.com/inward/record.url?scp=84872595173&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84872595173&partnerID=8YFLogxK
U2 - 10.1038/nature11803
DO - 10.1038/nature11803
M3 - Article
C2 - 23283171
AN - SCOPUS:84872595173
VL - 493
SP - 416
EP - 419
JO - Nature
JF - Nature
SN - 0028-0836
IS - 7432
ER -