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Updated: May 15, 2026
T-maze Forced Alternation and Left-right Discrimination Tasks for Assessing Working and Reference Memory in Mice
Published on: February 26, 2012
Prkcz null mice show normal learning and memory
Anna M Lee1, Benjamin R Kanter, Dan Wang
1Ernest Gallo Clinic and Research Center, Department of Neurology, University of California, San Francisco, 5858 Horton Street, Suite 200, Emeryville, California 94608, USA.
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.
Insights
Absence of protein kinase M-ζ (PKM-ζ) in mice did not impair learning or memory. Pharmacological inhibitors like ZIP can erase reward memory, even without PKM-ζ presence.
Area of Science:
- Neuroscience
- Molecular Biology
- Genetics
Background:
- Protein kinase M-ζ (PKM-ζ), a brain-specific kinase, is thought to maintain long-term memory.
- Previous studies relied on pharmacological inhibitors like ZIP to investigate PKM-ζ's role.
Purpose of the Study:
- To genetically investigate the role of PKM-ζ in learning and memory maintenance.
- To determine if PKM-ζ is essential for memory consolidation and erasure.
Main Methods:
- Generated Prkcz(-/-) mice lacking both PKC-ζ and PKM-ζ via genetic targeting.
- Assessed behavioral phenotypes including motor function, sensory perception, anxiety, and various learning/memory paradigms (fear conditioning, object recognition, cocaine CPP).
- Administered ZIP into the nucleus accumbens to assess reward memory erasure in knockout mice.
Main Results:
- Prkcz(-/-) mice exhibited normal behavior and learning/memory across multiple tests.
- These mice showed reduced anxiety-like behavior.
- ZIP injection successfully reduced cocaine-conditioned place preference, irrespective of PKM-ζ presence.
Conclusions:
- PKM-ζ is not essential for the maintenance of learning and memory in mice.
- The memory-erasing effects of ZIP are independent of PKM-ζ.
- Pharmacological inhibitors may have off-target effects or target other pathways involved in memory processes.
