Impaired Spatial Learning in α-Calcium-Calmodulin Kinase II Mutant Mice

American Association for the Advancement of Science (AAAS) - Tập 257 Số 5067 - Trang 206-211 - 1992
Alcino J. Silva1,2, Richard Paylor3, Jeanne M. Wehner3, Susumu Tonegawa1,4
1Center for Cancer Research and Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139.
2Howard Hughes Medical Institute, Center for Cancer Research, Cambridge, MA.
3Institute for Behavioral Genetics, University of Colorado, Boulder, CO 80309.
4Howard Hughes Medical Institute

Tóm tắt

Although long-term potentiation (LTP) has been studied as the mechanism for hippocampus-dependent learning and memory, evidence for this hypothesis is still incomplete. The mice with a mutation in the α-calcium-calmodulin-dependent kinase II (α-CaMKII), a synaptic protein enriched in the hippocampus, are appropriate for addressing this issue because the hippocampus of these mice is deficient in LTP but maintains intact postsynaptic mechanisms. These mutant mice exhibit specific learning impairments, an indication that α-CaMKII has a prominent role in spatial learning, but that it is not essential for some types of non-spatial learning. The data considerably strengthen the contention that the synaptic changes exhibited in LTP are the basis for spatial memory.

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Tài liệu tham khảo

Bekkers, J. M., Cold Spring Harbor Symposia on Quantitative Biology 55: 131 (1990).

BENSON, D.L., DIFFERENTIAL GENE-EXPRESSION FOR GLUTAMIC-ACID DECARBOXYLASE AND TYPE-II CALCIUM-CALMODULIN DEPENDENT PROTEIN-KINASE IN BASAL GANGLIA, THALAMUS, AND HYPOTHALAMUS OF THE MONKEY, JOURNAL OF NEUROSCIENCE 11: 1540 (1991).

10.1113/jphysiol.1973.sp010273

BLISS, T. V. P., JOURNAL OF PHYSIOLOGY-LONDON 232: 357 (1973).

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

CASTRO, C.A., RECOVERY OF SPATIAL-LEARNING DEFICITS AFTER DECAY OF ELECTRICALLY INDUCED SYNAPTIC ENHANCEMENT IN THE HIPPOCAMPUS, NATURE 342: 545 (1989).

COLLINGRIDGE, G.L., EXCITATORY AMINO-ACID RECEPTORS AND SYNAPTIC PLASTICITY, TRENDS IN PHARMACOLOGICAL SCIENCES 11: 290 (1990).

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

DAVIS, S, THE NMDA RECEPTOR ANTAGONIST D-2-AMINO-5-PHOSPHONOPENTANOATE (D-AP5) IMPAIRS SPATIAL-LEARNING AND LTP INVIVO AT INTRACEREBRAL CONCENTRATIONS COMPARABLE TO THOSE THAT BLOCK LTP INVITRO, JOURNAL OF NEUROSCIENCE 12: 21 (1992).

DOUGLAS, R.J., HIPPOCAMPAL-LESIONS AND ACTIVITY, PSYCHONOMIC SCIENCE 1: 187 (1964).

Eccles J. C. The Physiolofy of Synapse (1964).

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

FOREMAN, N.P., HEAD-DIPPING IN RATS WITH SUPERIOR COLLICULAR, MEDIAL FRONTAL CORTICAL AND HIPPOCAMPAL-LESIONS, PHYSIOLOGY & BEHAVIOR 30: 711 (1983).

HASTY, P, INTRODUCTION OF A SUBTLE MUTATION INTO THE HOX-2.6 LOCUS IN EMBRYONIC STEM-CELLS, NATURE 350: 243 (1991).

Hebb D. O. The Organization of Behavior (1949).

KEITH, J.R., WHY NMDA-RECEPTOR-DEPENDENT LONG-TERM POTENTIATION MAY NOT BE A MECHANISM OF LEARNING AND MEMORY - REAPPRAISAL OF THE NMDA-RECEPTOR BLOCKADE STRATEGY, PSYCHOBIOLOGY 18: 251 (1990).

Kelly, P. T., Proceedings of the National Academy of Sciences of the United States of America 81: 945 (1984).

Kennedy, M. B., Proceedings of the National Academy of Sciences of the United States of America 80: 7357 (1983).

KIMBLE, D.P., EFFECTS OF BILATERAL HIPPOCAMPAL LESIONS IN RATS, JOURNAL OF COMPARATIVE AND PHYSIOLOGICAL PSYCHOLOGY 56: 273 (1963).

LEATON, R.N., HABITUATION OF STARTLE RESPONSE, LICK SUPPRESSION, AND EXPLORATORY-BEHAVIOR IN RATS WITH HIPPOCAMPAL-LESIONS, JOURNAL OF COMPARATIVE AND PHYSIOLOGICAL PSYCHOLOGY 95: 813 (1981).

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

10.1126/science.2549638

MCNAUGHTON, B.L., SYNAPTIC ENHANCEMENT IN FASCIA DENTATA - COOPERATIVITY AMONG COACTIVE AFFERENTS, BRAIN RESEARCH 157: 277 (1978).

MORRIS, RGM, SPATIAL LOCALIZATION DOES NOT REQUIRE THE PRESENCE OF LOCAL CUES, LEARNING AND MOTIVATION 12: 239 (1981).

10.1038/297681a0

MORRIS, RGM, SELECTIVE IMPAIRMENT OF LEARNING AND BLOCKADE OF LONG-TERM POTENTIATION BY AN N-METHYL-D-ASPARTATE RECEPTOR ANTAGONIST, AP5, NATURE 319: 774 (1986).

10.1126/science.1900642

PAYLOR R unpublished data.

ROBERTS, W.W., J COMP PHYSIOL PSYCH 55: 695 (1986).

SCHWARTZKROIN, P.A., LONG-LASTING FACILITATION OF A SYNAPTIC POTENTIAL FOLLOWING TETANIZATION IN INVITRO HIPPOCAMPAL SLICE, BRAIN RESEARCH 89: 107 (1975).

10.1126/science.1378648

STAUBLI, U, ANTAGONISM OF NMDA RECEPTORS IMPAIRS ACQUISITION BUT NOT RETENTION OF OLFACTORY MEMORY, BEHAVIORAL NEUROSCIENCE 103: 54 (1989).

SUTHERLAND, R.J., SPATIAL-MAPPING - DEFINITIVE DISRUPTION BY HIPPOCAMPAL OR MEDIAL FRONTAL CORTICAL DAMAGE IN THE RAT, NEUROSCIENCE LETTERS 31: 271 (1982).

SUTHERLAND, R.J., SOC NEUR ABSTR 17: 483 (1991).

TEITELBAUM, H, ACTIVITY CHANGES FOLLOWING PARTIAL HIPPOCAMPAL LESIONS IN RATS, JOURNAL OF COMPARATIVE AND PHYSIOLOGICAL PSYCHOLOGY 56: 284 (1963).

UPCHURCH, M, DIFFERENCES BETWEEN INBRED STRAINS OF MICE IN MORRIS WATER MAZE PERFORMANCE, BEHAVIOR GENETICS 18: 55 (1988).

UPCHURCH, M, DBA/2IBG MICE ARE INCAPABLE OF CHOLINERGICALLY-BASED LEARNING IN THE MORRIS WATER TASK, PHARMACOLOGY BIOCHEMISTRY AND BEHAVIOR 29: 325 (1988).

WEHNER, J.M., HIPPOCAMPAL PROTEIN-KINASE-C ACTIVITY IS REDUCED IN POOR SPATIAL LEARNERS, BRAIN RESEARCH 523: 181 (1990).

WHISHAW, I.Q., DECORTICATION ABOLISHES PLACE BUT NOT CUE LEARNING IN RATS, BEHAVIOURAL BRAIN RESEARCH 11: 123 (1984).

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American Association for the Advancement of Science (AAAS)

Tập 257 Số 5067

206-211

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