Format

Send to

Choose Destination
Neurobiol Learn Mem. 2017 Feb;138:135-144. doi: 10.1016/j.nlm.2016.07.008. Epub 2016 Jul 11.

Persistent increased PKMζ in long-term and remote spatial memory.

Author information

1
Department of Physiology and Pharmacology, The Robert F. Furchgott Center for Neural and Behavioral Science, State University of New York Downstate Medical Center, Brooklyn, NY 11203, USA.
2
Department of Physiology and Pharmacology, The Robert F. Furchgott Center for Neural and Behavioral Science, State University of New York Downstate Medical Center, Brooklyn, NY 11203, USA; Department of Anesthesiology, State University of New York Downstate Medical Center, Brooklyn, NY 11203, USA.
3
Department of Psychology, Hunter College, City University of New York, NY 10021, USA.
4
Department of Pathology, State University of New York Downstate Medical Center, Brooklyn, NY 11203, USA.
5
Department of Anesthesiology, State University of New York Downstate Medical Center, Brooklyn, NY 11203, USA.
6
Department of Neurobiology and Anatomy, University of Texas Medical School at Houston, Houston, TX 77030, USA.
7
Department of Physiology and Pharmacology, The Robert F. Furchgott Center for Neural and Behavioral Science, State University of New York Downstate Medical Center, Brooklyn, NY 11203, USA; Center for Neural Science, New York University, New York, NY 10003, USA. Electronic address: afenton@nyu.edu.
8
Department of Physiology and Pharmacology, The Robert F. Furchgott Center for Neural and Behavioral Science, State University of New York Downstate Medical Center, Brooklyn, NY 11203, USA; Department of Anesthesiology, State University of New York Downstate Medical Center, Brooklyn, NY 11203, USA; Department of Neurology, State University of New York Downstate Medical Center, Brooklyn, NY 11203, USA. Electronic address: tsacktor@downstate.edu.

Abstract

PKMζ is an autonomously active PKC isoform that is thought to maintain both LTP and long-term memory. Whereas persistent increases in PKMζ protein sustain the kinase's action in LTP, the molecular mechanism for the persistent action of PKMζ during long-term memory has not been characterized. PKMζ inhibitors disrupt spatial memory when introduced into the dorsal hippocampus from 1day to 1month after training. Therefore, if the mechanisms of PKMζ's persistent action in LTP maintenance and long-term memory were similar, persistent increases in PKMζ would last for the duration of the memory, far longer than most other learning-induced gene products. Here we find that spatial conditioning by aversive active place avoidance or appetitive radial arm maze induces PKMζ increases in dorsal hippocampus that persist from 1day to 1month, coinciding with the strength and duration of memory retention. Suppressing the increase by intrahippocampal injections of PKMζ-antisense oligodeoxynucleotides prevents the formation of long-term memory. Thus, similar to LTP maintenance, the persistent increase in the amount of autonomously active PKMζ sustains the kinase's action during long-term and remote spatial memory maintenance.

KEYWORDS:

LTP; Long-term potentiation; Memory; PKM-zeta; PKMzeta

PMID:
27417578
PMCID:
PMC5501180
DOI:
10.1016/j.nlm.2016.07.008
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Elsevier Science Icon for PubMed Central
Loading ...
Support Center