PKMζ traces hippocampal LTP maintenance and spatial long-term memory

Autor: Hsieh, Changchi, Tsokas, Panayiotis, Chung, Ain, Garcia-Jou, Claudia, Lesburguères, Edith, Burghardt, Nesha S., Denny, Christine A., Flores-Obando, Rafael E., Rodríguez Valencia, Laura Melissa, Bergold, Peter, Cottrell, James E., Fenton, André Antonio, Sacktor, Todd Charlton
Jazyk: angličtina
Rok vydání: 2020
Předmět:
DOI: 10.1101/2020.02.05.936146
Popis: PKMζ is an autonomously active, atypical PKC isoform crucial for maintaining synaptic long-term potentiation (LTP) and long-term memory. Unlike other PKCs that are transiently activated by short-lived second messengers, PKMζ is persistently activated by long-lasting increases in the amount of the autonomously active kinase during LTP and long-term memory maintenance. Thus, localizing persistent increases in PKMζ might reveal traces of physiological LTP maintenance in the circuitry of the brain during long-term memory storage. Using quantitative immunohistochemistry validated by the lack of staining in PKMζ-null mice, we visualized the amount and distribution of PKMζ during LTP maintenance and spatial long-term memory storage in the hippocampal formation of wild-type mice. Strong afferent stimulation of Schaffer collateral/commissural fibers inducing LTP maintenance increases PKMζ in CA1 pyramidal cells for 2 hours in hippocampal slices. Active place avoidance spatial conditioning increases PKMζ in CA1 pyramidal cells of the hippocampal formation from 1 day to at least 1 month. The increases in PKMζ coincide with the location of cells marked during long-term memory training by Arc promoter-mediated expression of a fluorescent protein, including at dendritic spines. We conclude that increased PKMζ forms persistent traces in CA1 pyramidal cells that are sites of molecular information storage during LTP maintenance and spatial long-term memory. Graphical Abstract PKMζ-immunohistochemistry reveals persistent increased PKMζ in the hippocampus during (A) LTP maintenance, and (B) spatial long-term memory storage.
Databáze: OpenAIRE