Journal article
Myristoylated alanine rich C kinase substrate (MARCKS) heterozygous mutant mice exhibit deficits in hippocampal mossy fiber-CA3 long-term potentiation
Hippocampus, Vol.16(5), pp.495-503
2006
DOI: 10.1002/hipo.20177
PMCID: PMC2914311
PMID: 16572394
Abstract
The myristoylated alanine-rich C kinase substrate (MARCKS) is a primary protein kinase C (PKC) substrate in brain thought to transduce PKC signaling into alterations in the filamentous (F) actin cytoskeleton. Within the adult hippocampus, MARCKS is highly expressed in the dentate gyrus (DG)-CA3 mossy fiber pathway, but is expressed at low levels in the CA3-CA1 Schaffer collateral-CA1 pathway. We have previously demonstrated that 50% reductions in MARCKS expression in heterozygous Marcks mutant mice produce robust deficits in spatial reversal learning, but not contextual fear conditioning, suggesting that only specific aspects of hippocampal function are impaired by reduction in MARCKS expression. To further elucidate the role of MARCKS in hippocampal synaptic plasticity, in the present study we examined basal synaptic transmission, paired-pulse facilitation, post-tetanic potentiation, and long-term potentiation (LTP) in the hippocampal mossy fiber-CA3 and Schaffer collateral-CA1 pathways of heterozygous Marcks mutant and wild-type mice. We found that LTP is significantly impaired in the mossy fiber-CA3 pathway, but not in the Schaffer collateral-CA1 pathway, in heterozygous Marcks mutant mice, whereas basal synaptic transmission, paired-pulse facilitation, and post-tetanic potentiation are unaffected in both pathways. These findings indicate that a 50% reduction in MARCKS expression impairs processes required for long-term, but not short-term, synaptic plasticity in the mossy fiber-CA3 pathway. The implications of these findings for the role of the mossy fiber-CA3 pathway in hippocampus-dependent learning processes are discussed.
Details
- Title: Subtitle
- Myristoylated alanine rich C kinase substrate (MARCKS) heterozygous mutant mice exhibit deficits in hippocampal mossy fiber-CA3 long-term potentiation
- Creators
- Rifat J Hussain - Department of Psychiatry, University of Pennsylvania School of Medicine, Clinical Research Building, Philadelphia, Pennsylvania, USADeborah J StumpoPerry J BlackshearRobert H LenoxTed AbelRobert K McNamara
- Resource Type
- Journal article
- Publication Details
- Hippocampus, Vol.16(5), pp.495-503
- DOI
- 10.1002/hipo.20177
- PMID
- 16572394
- PMCID
- PMC2914311
- NLM abbreviation
- Hippocampus
- ISSN
- 1050-9631
- eISSN
- 1098-1063
- Publisher
- United States
- Grant note
- P30 HD026979 / NICHD NIH HHS R01 MH060244 / NIMH NIH HHS R01 AG18199 / NIA NIH HHS R01 MH060244-06A1 / NIMH NIH HHS HD26979 / NICHD NIH HHS R01 MH59959 / NIMH NIH HHS R01 MH60244 / NIMH NIH HHS
- Language
- English
- Date published
- 2006
- Academic Unit
- Molecular Physiology and Biophysics; Psychiatry; Psychological and Brain Sciences; Iowa Neuroscience Institute; Neuroscience and Pharmacology; Biochemistry and Molecular Biology
- Record Identifier
- 9984065834402771
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