Journal article
Effect of myristoylated alanine‐rich C kinase substrate (MARCKS) overexpression on hippocampus‐dependent learning and hippocampal synaptic plasticity in MARCKS transgenic mice
Hippocampus, Vol.15(5), pp.675-683
2005
DOI: 10.1002/hipo.20089
PMID: 15889447
Abstract
The myristoylated alanine‐rich C kinase substrate (MARCKS) is a primary substrate of protein kinase C (PKC) thought to regulate membrane‐filamentous actin cytoskeletal plasticity in response to PKC activity in the regulation of synaptic efficacy. We have recently reported that MARCKS expression is significantly elevated (45%) in the hippocampus of DBA/2J mice, which exhibit impaired hippocampus‐dependent learning and hippocampal long‐term potentiation (LTP), compared with C57BL/6J mice. The latter finding led us to hypothesize that elevations in MARCKS expression are detrimental to hippocampal plasticity and function. To assess this more directly, we examined hippocampal (CA1) paired‐pulse facilitation and LTP, and hippocampus‐dependent learning in mice overexpressing MARCKS through the expression of a human MARCKS transgene (Tg+). The human MARCKS protein was confirmed to be expressed in the hippocampus of Tg+ mice but not in Tg− mice. Schaffer collateral paired‐pulse facilitation, input‐output responses, and LTP did not differ between Tg+ and Tg− mice, indicating that neurotransmitter release, short‐term, and long‐term synaptic plasticity are not impaired by MARCKS overexpression. In the Morris water maze, Tg+ mice exhibited a mild but significant spatial learning impairment during initial acquisition, and a more severe impairment during reversal training. Tg+ did not exhibit impaired swim speed or visible platform performance relative to Tg− mice, indicating the absence of gross sensorimotor deficits. Fear conditioning to either context or cue was not impaired in Tg+ mice. Behavioral deficits could not be attributed to differences in hippocampal PKC isozyme (α βII, γ, ϵ, ζ) or calmodulin expression, or alterations in hippocampal cytoarchitecture or infrapyramidal mossy fiber limb length. Collectively, these results indicate that elevations in MARCKS expression are detrimental to specific aspects of hippocampal function. © 2005 Wiley‐Liss, Inc.
Details
- Title: Subtitle
- Effect of myristoylated alanine‐rich C kinase substrate (MARCKS) overexpression on hippocampus‐dependent learning and hippocampal synaptic plasticity in MARCKS transgenic mice
- Creators
- Robert K McNamaraRifat J HussainErica J SimonDeborah J StumpoPerry J BlackshearTed AbelRobert H Lenox
- Resource Type
- Journal article
- Publication Details
- Hippocampus, Vol.15(5), pp.675-683
- Publisher
- Wiley Subscription Services, Inc., A Wiley Company; Hoboken
- DOI
- 10.1002/hipo.20089
- PMID
- 15889447
- ISSN
- 1050-9631
- eISSN
- 1098-1063
- Number of pages
- 9
- Grant note
- NIMH (RO1 MH59959; RO1 MH60244) Mental Retardation and Development Disabilities Research Center, Children's Hospital of Philadelphia (HD26979) NIA (RO1 AG18199) University of Pennsylvania Research Foundation Whitehall Foundation
- Language
- English
- Date published
- 2005
- Academic Unit
- Molecular Physiology and Biophysics; Psychiatry; Psychological and Brain Sciences; Iowa Neuroscience Institute; Neuroscience and Pharmacology; Biochemistry and Molecular Biology
- Record Identifier
- 9984065733802771
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