Deficient Hippocampal Long-Term Potentiation in α-Calcium-Calmodulin Kinase II Mutant Mice

American Association for the Advancement of Science (AAAS) - Tập 257 Số 5067 - Trang 201-206 - 1992
Alcino J. Silva1,2, Charles F. Stevens1,2, Susumu Tonegawa2,3, Yanyan Wang2,3
1Center for Cancer Research and Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139.
2Howard Hughes Medical Institute
3Salk Institute, La Jolla, CA 92037.

Tóm tắt

As a first step in a program to use genetically altered mice in the study of memory mechanisms, mutant mice were produced that do not express the α-calcium-calmodulin-dependent kinase II (α-CaMKII). The α-CaMKII is highly enriched in postsynaptic densities of hippocampus and neocortex and may be involved in the regulation of long-term potentiation (LTP). Such mutant mice exhibited mostly normal behaviors and presented no obvious neuroanatomical defects. Whole cell recordings reveal that postsynaptic mechanisms, including N -methyl-D-aspartate (NMDA) receptor function, are intact. Despite normal postsynaptic mechanisms, these mice are deficient in their ability to produce LTP and are therefore a suitable model for studying the relation between LTP and learning processes.

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Tài liệu tham khảo

ADRA, C.N., CLONING AND EXPRESSION OF THE MOUSE PGK-1 GENE AND THE NUCLEOTIDE-SEQUENCE OF ITS PROMOTER, GENE 60: 65 (1987).

10.1038/346724a0

10.1113/jphysiol.1973.sp010273

BURGIN, K.E., INSITU HYBRIDIZATION HISTOCHEMISTRY OF CA-2+ CALMODULIN-DEPENDENT PROTEIN-KINASE IN DEVELOPING RAT-BRAIN, JOURNAL OF NEUROSCIENCE 10: 1788 (1990).

10.1126/science.2660260

10.1038/356521a0

COLBRAN, R.J., CALCIUM CALMODULIN-DEPENDENT PROTEIN KINASE-II, BIOCHEMICAL JOURNAL 258: 313 (1989).

DAVIS, M, THE ROLE OF THE AMYGDALA IN FEAR-POTENTIATED STARTLE - IMPLICATIONS FOR ANIMAL-MODELS OF ANXIETY, TRENDS IN PHARMACOLOGICAL SCIENCES 13: 35 (1992).

DOUGLAS, R.J., HIPPOCAMPUS AND BEHAVIOR, PSYCHOLOGICAL BULLETIN 67: 416 (1967).

ERONDU, N.E., REGIONAL DISTRIBUTION OF TYPE-II CA-2+ CALMODULIN-DEPENDENT PROTEIN-KINASE IN RAT-BRAIN, JOURNAL OF NEUROSCIENCE 5: 3270 (1985).

FALLS, W.A., EXTINCTION OF FEAR-POTENTIATED STARTLE - BLOCKADE BY INFUSION OF AN NMDA ANTAGONIST INTO THE AMYGDALA, JOURNAL OF NEUROSCIENCE 12: 854 (1992).

10.1038/354076a0

HANSON, P.I., EXPRESSION OF A MULTIFUNCTIONAL CA-2+ CALMODULIN-DEPENDENT PROTEIN-KINASE AND MUTATIONAL ANALYSIS OF ITS AUTO-REGULATION, NEURON 3: 59 (1989).

JAHR, C.E., A QUANTITATIVE DESCRIPTION OF NMDA RECEPTOR-CHANNEL KINETIC-BEHAVIOR, JOURNAL OF NEUROSCIENCE 10: 1830 (1990).

JAHR, C.E., VOLTAGE DEPENDENCE OF NMDA-ACTIVATED MACROSCOPIC CONDUCTANCES PREDICTED BY SINGLE-CHANNEL KINETICS, JOURNAL OF NEUROSCIENCE 10: 3178 (1990).

LIN, J.W., EFFECTS OF SYNAPSIN-I AND CALCIUM CALMODULIN-DEPENDENT PROTEIN KINASE-II ON SPONTANEOUS NEUROTRANSMITTER RELEASE IN THE SQUID GIANT SYNAPSE, PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA 87: 8257 (1990).

LISMAN, J.E., FEASIBILITY OF LONG-TERM STORAGE OF GRADED INFORMATION BY THE CA-2+/CALMODULIN-DEPENDENT PROTEIN-KINASE MOLECULES OF THE POSTSYNAPTIC DENSITY, PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA 85: 5320 (1988).

MALENKA, R.C., AN ESSENTIAL ROLE FOR POSTSYNAPTIC CALMODULIN AND PROTEIN-KINASE ACTIVITY IN LONG-TERM POTENTIATION, NATURE 340: 554 (1989).

MALINOW, R, PRESYNAPTIC ENHANCEMENT SHOWN BY WHOLE-CELL RECORDINGS OF LONG-TERM POTENTIATION IN HIPPOCAMPAL SLICES, NATURE 346: 177 (1990).

10.1126/science.2549638

McGuinness, T. L., Journal of Biological Chemistry 260: 1696 (1985).

MILLER, S.G., REGULATION OF BRAIN TYPE-II CA-2+ CALMODULIN-DEPENDENT PROTEIN-KINASE BY AUTOPHOSPHORYLATION - A CA-2+-TRIGGERED MOLECULAR SWITCH, CELL 44: 861 (1986).

MILLER, S.G., SEQUENCES OF AUTOPHOSPHORYLATION SITES IN NEURONAL TYPE-II CAM KINASE THAT CONTROL CA-2+-INDEPENDENT ACTIVITY, NEURON 1: 593 (1988).

Morris R. G. M. Long-Term Potentiation: A Debate of Current Issue (1991).

10.1038/354073a0

SCHULMAN, H, MULTIFUNCTIONAL CA-2+/CALMODULIN-DEPENDENT PROTEIN-KINASE - DOMAIN-STRUCTURE AND REGULATION, TRENDS IN BIOCHEMICAL SCIENCES 14: 62 (1989).

10.1126/science.1321493

SILVA A.J. unpublished data.

THOMPSON, S, GERM LINE TRANSMISSION AND EXPRESSION OF A CORRECTED HPRT GENE PRODUCED BY GENE TARGETING IN EMBRYONIC STEM-CELLS, CELL 56: 313 (1989).