title: Early memory formation disrupted by atypical PKC inhibitor ZIP in the medial prefrontal cortex but not hippocampus.
abstract: Atypical isoforms of protein kinase C (aPKCs; particularly protein kinase M zeta: PKMζ) have been hypothesized to be necessary and sufficient for the maintenance of long-term potentiation (LTP) and long term memory by maintaining postsynaptic AMPA receptors via the GluA2 subunit. A myristoylated PKMζ pseudosubstrate peptide (ZIP) blocks PKMζ activity. We examined the actions of ZIP in medial prefrontal cortex (mPFC) and hippocampus in associative recognition memory in rats during early memory formation and memory maintenance. ZIP infusion in either hippocampus or mPFC impaired memory maintenance. However, early memory formation was impaired by ZIP in mPFC but not hippocampus; and blocking GluA2-dependent removal of AMPA receptors did not affect this impairment caused by ZIP in the mPFC. The findings indicate: (i) a difference in the actions of ZIP in hippocampus and medial prefrontal cortex, and (ii) a GluA2-independent target of ZIP (possibly PKCλ) in the mPFC during early memory formation.
authors.affiliation: Department of Physiology and Pharmacology, University of Bristol, School of Medical Sciences, Bristol, BS8 1TD, United Kingdom.
authors.forename: Obaro
authors.initials: O
authors.lastname: Evuarherhe
authors.forename: Gareth R I
authors.initials: GR
authors.lastname: Barker
authors.forename: Giorgia
authors.initials: G
authors.lastname: Savalli
authors.forename: Elizabeth C
authors.initials: EC
authors.lastname: Warburton
authors.forename: Malcolm W
authors.initials: MW
authors.lastname: Brown
mesh_terms: D000818:Animals; D001245:Association Learning / Q000187:drug effects / Q000502:physiology; D057846:Cell-Penetrating Peptides; D004705:Endocytosis / Q000187:drug effects / Q000502:physiology; D005106:Exploratory Behavior / Q000187:drug effects / Q000502:physiology; D006624:Hippocampus / Q000187:drug effects* / Q000502:physiology; D055666:Lipopeptides / Q000494:pharmacology*; D008297:Male; D008568:Memory / Q000187:drug effects* / Q000502:physiology; D009483:Neuropsychological Tests; D017397:Prefrontal Cortex / Q000187:drug effects* / Q000502:physiology; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism; D047428:Protein Kinase Inhibitors / Q000494:pharmacology*; D051381:Rats; D018091:Receptors, AMPA / Q000037:antagonists & inhibitors / Q000378:metabolism
chemical_list: D057846:Cell-Penetrating Peptides; D055666:Lipopeptides; D047428:Protein Kinase Inhibitors; D018091:Receptors, AMPA; C568285:zeta-inhibitory peptide; D011493:Protein Kinase C; C504730:protein kinase M zeta, rat; C104722:glutamate receptor ionotropic, AMPA 2
keywords: encoding; hippocampus; maintenance; medial prefrontal cortex; recognition memory
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