Reviewer #1 (Public review): PKMζ-PKCι/λ double-knockout demonstrates atypical PKC is crucial for the persistence of hippocampal LTP and spatial memory

Le résumé fourni par la source

Is long-term memory maintained by stable synaptic structures or persistent biochemical action? PKMζ, a persistently active atypical PKC (aPKC), is thought to be crucial for maintaining the late phase of long-term potentiation (late-LTP) and long-term memory through sustained kinase action. However, PKMζ-knockout mice express hippocampal LTP and spatial memory while lacking neocortical LTP, calling into question whether persistent kinases and PKMζ are fundamental to LTP and memory. In , we showed PKCι/λ, the other aPKC, is the most likely compensating PKC isoform in PKMζ-knockout mice. In wild-type mice, PKCι/λ is critical to the initial generation of early-LTP and short-term memory, and PKMζ compensates for genetic deletion of PKCι/λ by supporting both early- and late-phase processes. Here, we found PKCι/λ persists in LTP and long-term memory when PKMζ is genetically deleted. We tested whether PKCι/λ functionally compensates for the loss of PKMζ by genetically ablating both aPKCs. Whereas deleting PKMζ and PKCι/λ individually induces compensation, deleting both aPKCs abolishes hippocampal late-LTP. Hippocampal ι/λ-ζ-double-knockout eliminates spatial long-term memory but not short-term memory. Thus, in the absence of PKMζ, a second persistent biochemical process compensates to maintain late-LTP and long-term memory.

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