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Myristoylated alanine rich C kinase substrate (MARCKS) heterozygous mutant mice exhibit deficits in hippocampal mossy fiber-CA3 long-term potentiation.
Hippocampus 2006; 16(5):495-503H

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.

Authors+Show Affiliations

Department of Psychiatry, University of Pennsylvania School of Medicine, Clinical Research Building, Philadelphia, Pennsylvania, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

16572394

Citation

Hussain, Rifat J., et al. "Myristoylated Alanine Rich C Kinase Substrate (MARCKS) Heterozygous Mutant Mice Exhibit Deficits in Hippocampal Mossy fiber-CA3 Long-term Potentiation." Hippocampus, vol. 16, no. 5, 2006, pp. 495-503.
Hussain RJ, Stumpo DJ, Blackshear PJ, et al. Myristoylated alanine rich C kinase substrate (MARCKS) heterozygous mutant mice exhibit deficits in hippocampal mossy fiber-CA3 long-term potentiation. Hippocampus. 2006;16(5):495-503.
Hussain, R. J., Stumpo, D. J., Blackshear, P. J., Lenox, R. H., Abel, T., & McNamara, R. K. (2006). Myristoylated alanine rich C kinase substrate (MARCKS) heterozygous mutant mice exhibit deficits in hippocampal mossy fiber-CA3 long-term potentiation. Hippocampus, 16(5), pp. 495-503.
Hussain RJ, et al. Myristoylated Alanine Rich C Kinase Substrate (MARCKS) Heterozygous Mutant Mice Exhibit Deficits in Hippocampal Mossy fiber-CA3 Long-term Potentiation. Hippocampus. 2006;16(5):495-503. PubMed PMID: 16572394.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Myristoylated alanine rich C kinase substrate (MARCKS) heterozygous mutant mice exhibit deficits in hippocampal mossy fiber-CA3 long-term potentiation. AU - Hussain,Rifat J, AU - Stumpo,Deborah J, AU - Blackshear,Perry J, AU - Lenox,Robert H, AU - Abel,Ted, AU - McNamara,Robert K, PY - 2006/3/31/pubmed PY - 2006/6/22/medline PY - 2006/3/31/entrez SP - 495 EP - 503 JF - Hippocampus JO - Hippocampus VL - 16 IS - 5 N2 - 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. SN - 1050-9631 UR - https://www.unboundmedicine.com/medline/citation/16572394/Myristoylated_alanine_rich_C_kinase_substrate__MARCKS__heterozygous_mutant_mice_exhibit_deficits_in_hippocampal_mossy_fiber_CA3_long_term_potentiation_ L2 - https://doi.org/10.1002/hipo.20177 DB - PRIME DP - Unbound Medicine ER -