Inducible, pharmacogenetic approaches to the study of learning and memory
Here we introduce a strategy in which pharmacology is used to induce the effects of recessive mutations. For example, mice heterozygous for a null mutation of the K- ras gene (K- ras +/− ) show normal hippocampal mitogen-activated protein kinase (MAPK) activation, long-term potentiation (LTP) and co...
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| Veröffentlicht in: | Nature neuroscience 2001-12, Vol.4 (12), p.1238-1243 |
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| creator | Ohno, Masuo Frankland, Paul W. Chen, Adele P. Costa, Rui M. Silva, Alcino J. |
| description | Here we introduce a strategy in which pharmacology is used to induce the effects of recessive mutations. For example, mice heterozygous for a null mutation of the K-
ras
gene (K-
ras
+/−
) show normal hippocampal mitogen-activated protein kinase (MAPK) activation, long-term potentiation (LTP) and contextual conditioning. However, a dose of a mitogen-activated/extracellular-signal-regulated kinase (MEK) inhibitor, ineffective in wild-type controls, blocks MAPK activation, LTP and contextual learning in K-
ras
+/−
mutants. These indicate that K-Ras/MEK/MAPK signaling is critical in synaptic and behavioral plasticity. A subthreshold dose of NMDA receptor antagonists triggered a contextual learning deficit in mice heterozygous for a point mutation (T286A) in the αCaMKII gene, but not in K-
ras
+/−
mutants, demonstrating the specificity of the synergistic interaction between the MEK inhibitor and the K-
ras
+/−
mutation. This pharmacogenetic approach combines the high temporal specificity that pharmacological manipulations offer, with the molecular specificity of genetic disruptions. |
| doi_str_mv | 10.1038/nn771 |
| format | Article |
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ras
gene (K-
ras
+/−
) show normal hippocampal mitogen-activated protein kinase (MAPK) activation, long-term potentiation (LTP) and contextual conditioning. However, a dose of a mitogen-activated/extracellular-signal-regulated kinase (MEK) inhibitor, ineffective in wild-type controls, blocks MAPK activation, LTP and contextual learning in K-
ras
+/−
mutants. These indicate that K-Ras/MEK/MAPK signaling is critical in synaptic and behavioral plasticity. A subthreshold dose of NMDA receptor antagonists triggered a contextual learning deficit in mice heterozygous for a point mutation (T286A) in the αCaMKII gene, but not in K-
ras
+/−
mutants, demonstrating the specificity of the synergistic interaction between the MEK inhibitor and the K-
ras
+/−
mutation. This pharmacogenetic approach combines the high temporal specificity that pharmacological manipulations offer, with the molecular specificity of genetic disruptions.</description><identifier>ISSN: 1097-6256</identifier><identifier>EISSN: 1546-1726</identifier><identifier>DOI: 10.1038/nn771</identifier><identifier>PMID: 11713472</identifier><identifier>CODEN: NANEFN</identifier><language>eng</language><publisher>New York: Nature Publishing Group US</publisher><subject>aCaMKII gene ; Animal Genetics and Genomics ; Animals ; Avoidance Learning - drug effects ; Avoidance Learning - physiology ; Axons - drug effects ; Axons - metabolism ; Behavioral Sciences ; Biological Techniques ; Biomedical and Life Sciences ; Biomedicine ; Calcium-Calmodulin-Dependent Protein Kinase Type 2 ; Calcium-Calmodulin-Dependent Protein Kinases - deficiency ; Calcium-Calmodulin-Dependent Protein Kinases - genetics ; Conditioning (Psychology) - drug effects ; Conditioning (Psychology) - physiology ; Electric Stimulation ; Enzyme Inhibitors - pharmacology ; Excitatory Amino Acid Antagonists - pharmacology ; Excitatory Postsynaptic Potentials - drug effects ; Excitatory Postsynaptic Potentials - physiology ; Fear - drug effects ; Fear - physiology ; Female ; Gene targeting ; Genes, ras - drug effects ; Genes, ras - physiology ; Genetic aspects ; Heterozygote ; Hippocampus - drug effects ; Hippocampus - metabolism ; K-Ras gene ; Kinases ; Learning ; Learning - drug effects ; Learning - physiology ; Long-Term Potentiation - drug effects ; Long-Term Potentiation - physiology ; Male ; MAP Kinase Kinase 1 ; MAP Kinase Signaling System - drug effects ; MAP Kinase Signaling System - physiology ; Memory ; Memory - drug effects ; Memory - physiology ; Mice ; Mice, Knockout ; Mitogen-Activated Protein Kinase Kinases - antagonists & inhibitors ; Mitogen-Activated Protein Kinase Kinases - metabolism ; Mitogen-Activated Protein Kinases - antagonists & inhibitors ; Mitogen-Activated Protein Kinases - metabolism ; Mutation ; Mutation - drug effects ; Mutation - physiology ; Neurobiology ; Neurosciences ; Pharmacogenetics ; Phosphorylation ; Physiological aspects ; Protein-Serine-Threonine Kinases - antagonists & inhibitors ; Protein-Serine-Threonine Kinases - metabolism ; Proteins ; Publishing ; Receptors, N-Methyl-D-Aspartate - antagonists & inhibitors ; Receptors, N-Methyl-D-Aspartate - metabolism ; Stem cells</subject><ispartof>Nature neuroscience, 2001-12, Vol.4 (12), p.1238-1243</ispartof><rights>Springer Nature America, Inc. 2001</rights><rights>COPYRIGHT 2001 Nature Publishing Group</rights><rights>Copyright Nature Publishing Group Dec 2001</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c467t-f4736f871c03875014fb2626eb4996406328a65fde2e73ea368dc189937211f63</citedby><cites>FETCH-LOGICAL-c467t-f4736f871c03875014fb2626eb4996406328a65fde2e73ea368dc189937211f63</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1038/nn771$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1038/nn771$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>314,776,780,27901,27902,41464,42533,51294</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/11713472$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Ohno, Masuo</creatorcontrib><creatorcontrib>Frankland, Paul W.</creatorcontrib><creatorcontrib>Chen, Adele P.</creatorcontrib><creatorcontrib>Costa, Rui M.</creatorcontrib><creatorcontrib>Silva, Alcino J.</creatorcontrib><title>Inducible, pharmacogenetic approaches to the study of learning and memory</title><title>Nature neuroscience</title><addtitle>Nat Neurosci</addtitle><addtitle>Nat Neurosci</addtitle><description>Here we introduce a strategy in which pharmacology is used to induce the effects of recessive mutations. For example, mice heterozygous for a null mutation of the K-
ras
gene (K-
ras
+/−
) show normal hippocampal mitogen-activated protein kinase (MAPK) activation, long-term potentiation (LTP) and contextual conditioning. However, a dose of a mitogen-activated/extracellular-signal-regulated kinase (MEK) inhibitor, ineffective in wild-type controls, blocks MAPK activation, LTP and contextual learning in K-
ras
+/−
mutants. These indicate that K-Ras/MEK/MAPK signaling is critical in synaptic and behavioral plasticity. A subthreshold dose of NMDA receptor antagonists triggered a contextual learning deficit in mice heterozygous for a point mutation (T286A) in the αCaMKII gene, but not in K-
ras
+/−
mutants, demonstrating the specificity of the synergistic interaction between the MEK inhibitor and the K-
ras
+/−
mutation. This pharmacogenetic approach combines the high temporal specificity that pharmacological manipulations offer, with the molecular specificity of genetic disruptions.</description><subject>aCaMKII gene</subject><subject>Animal Genetics and Genomics</subject><subject>Animals</subject><subject>Avoidance Learning - drug effects</subject><subject>Avoidance Learning - physiology</subject><subject>Axons - drug effects</subject><subject>Axons - metabolism</subject><subject>Behavioral Sciences</subject><subject>Biological Techniques</subject><subject>Biomedical and Life Sciences</subject><subject>Biomedicine</subject><subject>Calcium-Calmodulin-Dependent Protein Kinase Type 2</subject><subject>Calcium-Calmodulin-Dependent Protein Kinases - deficiency</subject><subject>Calcium-Calmodulin-Dependent Protein Kinases - genetics</subject><subject>Conditioning (Psychology) - drug effects</subject><subject>Conditioning (Psychology) - physiology</subject><subject>Electric Stimulation</subject><subject>Enzyme Inhibitors - pharmacology</subject><subject>Excitatory Amino Acid Antagonists - pharmacology</subject><subject>Excitatory Postsynaptic Potentials - drug effects</subject><subject>Excitatory Postsynaptic Potentials - physiology</subject><subject>Fear - drug effects</subject><subject>Fear - physiology</subject><subject>Female</subject><subject>Gene targeting</subject><subject>Genes, ras - drug effects</subject><subject>Genes, ras - physiology</subject><subject>Genetic aspects</subject><subject>Heterozygote</subject><subject>Hippocampus - drug effects</subject><subject>Hippocampus - metabolism</subject><subject>K-Ras gene</subject><subject>Kinases</subject><subject>Learning</subject><subject>Learning - drug effects</subject><subject>Learning - physiology</subject><subject>Long-Term Potentiation - drug effects</subject><subject>Long-Term Potentiation - physiology</subject><subject>Male</subject><subject>MAP Kinase Kinase 1</subject><subject>MAP Kinase Signaling System - drug effects</subject><subject>MAP Kinase Signaling System - physiology</subject><subject>Memory</subject><subject>Memory - drug effects</subject><subject>Memory - physiology</subject><subject>Mice</subject><subject>Mice, Knockout</subject><subject>Mitogen-Activated Protein Kinase Kinases - antagonists & inhibitors</subject><subject>Mitogen-Activated Protein Kinase Kinases - metabolism</subject><subject>Mitogen-Activated Protein Kinases - antagonists & inhibitors</subject><subject>Mitogen-Activated Protein Kinases - metabolism</subject><subject>Mutation</subject><subject>Mutation - drug effects</subject><subject>Mutation - physiology</subject><subject>Neurobiology</subject><subject>Neurosciences</subject><subject>Pharmacogenetics</subject><subject>Phosphorylation</subject><subject>Physiological aspects</subject><subject>Protein-Serine-Threonine Kinases - antagonists & inhibitors</subject><subject>Protein-Serine-Threonine Kinases - metabolism</subject><subject>Proteins</subject><subject>Publishing</subject><subject>Receptors, N-Methyl-D-Aspartate - antagonists & inhibitors</subject><subject>Receptors, N-Methyl-D-Aspartate - metabolism</subject><subject>Stem cells</subject><issn>1097-6256</issn><issn>1546-1726</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2001</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><recordid>eNqFktuKFDEQhhtR3IP7ChIEXQR7zTnpy2XxMLAgeLgOmXSlp5fuZEzS4Ly9WWdgGC-UXFRIvlT9f6Wa5orgG4KZfh-CUuRJc04Ely1RVD6te9ypVlIhz5qLnB8wxkro7nlzRogijCt63qxWoV_cuJ7gHdpubJqtiwMEKKNDdrtN0boNZFQiKhtAuSz9DkWPJrApjGFANvRohjmm3YvmmbdThqtDvGx-fPzw_e5ze__l0-ru9r51XKrSeq6Y9FoRV1UrgQn3ayqphDXvOsmxZFRbKXwPFBQDy6TuHdFdxxQlxEt22Vzv81ZxPxfIxcxjdjBNNkBcstFEScyo4pV8809SUYY5k_K_INGM0tqxCr76C3yISwrVrqkFlSa8oxW62UODncCMwceSrKurh3l0MYAf6_kt0UJIIdRj-bcnDypT4FcZ7JKzWX37esq-3rMuxZwTeLNN42zTzhBsHgfB_BmEyr08KF3WM_RH6vDzR8-5XoUB0tHKaabfF3u2Fw</recordid><startdate>20011201</startdate><enddate>20011201</enddate><creator>Ohno, Masuo</creator><creator>Frankland, Paul W.</creator><creator>Chen, Adele P.</creator><creator>Costa, Rui M.</creator><creator>Silva, Alcino J.</creator><general>Nature Publishing Group US</general><general>Nature Publishing Group</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>ISR</scope><scope>3V.</scope><scope>7QG</scope><scope>7QP</scope><scope>7QR</scope><scope>7TK</scope><scope>7TM</scope><scope>7U7</scope><scope>7U9</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>88G</scope><scope>8AO</scope><scope>8FD</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>C1K</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M2M</scope><scope>M7P</scope><scope>P64</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>PSYQQ</scope><scope>Q9U</scope><scope>RC3</scope><scope>7X8</scope></search><sort><creationdate>20011201</creationdate><title>Inducible, pharmacogenetic approaches to the study of learning and memory</title><author>Ohno, Masuo ; Frankland, Paul W. ; Chen, Adele P. ; Costa, Rui M. ; Silva, Alcino J.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c467t-f4736f871c03875014fb2626eb4996406328a65fde2e73ea368dc189937211f63</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2001</creationdate><topic>aCaMKII gene</topic><topic>Animal Genetics and Genomics</topic><topic>Animals</topic><topic>Avoidance Learning - drug effects</topic><topic>Avoidance Learning - physiology</topic><topic>Axons - drug effects</topic><topic>Axons - metabolism</topic><topic>Behavioral Sciences</topic><topic>Biological Techniques</topic><topic>Biomedical and Life Sciences</topic><topic>Biomedicine</topic><topic>Calcium-Calmodulin-Dependent Protein Kinase Type 2</topic><topic>Calcium-Calmodulin-Dependent Protein Kinases - deficiency</topic><topic>Calcium-Calmodulin-Dependent Protein Kinases - genetics</topic><topic>Conditioning (Psychology) - drug effects</topic><topic>Conditioning (Psychology) - physiology</topic><topic>Electric Stimulation</topic><topic>Enzyme Inhibitors - pharmacology</topic><topic>Excitatory Amino Acid Antagonists - pharmacology</topic><topic>Excitatory Postsynaptic Potentials - drug effects</topic><topic>Excitatory Postsynaptic Potentials - physiology</topic><topic>Fear - drug effects</topic><topic>Fear - physiology</topic><topic>Female</topic><topic>Gene targeting</topic><topic>Genes, ras - drug effects</topic><topic>Genes, ras - physiology</topic><topic>Genetic aspects</topic><topic>Heterozygote</topic><topic>Hippocampus - drug effects</topic><topic>Hippocampus - metabolism</topic><topic>K-Ras gene</topic><topic>Kinases</topic><topic>Learning</topic><topic>Learning - drug effects</topic><topic>Learning - physiology</topic><topic>Long-Term Potentiation - drug effects</topic><topic>Long-Term Potentiation - physiology</topic><topic>Male</topic><topic>MAP Kinase Kinase 1</topic><topic>MAP Kinase Signaling System - drug effects</topic><topic>MAP Kinase Signaling System - physiology</topic><topic>Memory</topic><topic>Memory - drug effects</topic><topic>Memory - physiology</topic><topic>Mice</topic><topic>Mice, Knockout</topic><topic>Mitogen-Activated Protein Kinase Kinases - antagonists & inhibitors</topic><topic>Mitogen-Activated Protein Kinase Kinases - metabolism</topic><topic>Mitogen-Activated Protein Kinases - antagonists & inhibitors</topic><topic>Mitogen-Activated Protein Kinases - metabolism</topic><topic>Mutation</topic><topic>Mutation - drug effects</topic><topic>Mutation - physiology</topic><topic>Neurobiology</topic><topic>Neurosciences</topic><topic>Pharmacogenetics</topic><topic>Phosphorylation</topic><topic>Physiological aspects</topic><topic>Protein-Serine-Threonine Kinases - antagonists & inhibitors</topic><topic>Protein-Serine-Threonine Kinases - metabolism</topic><topic>Proteins</topic><topic>Publishing</topic><topic>Receptors, N-Methyl-D-Aspartate - antagonists & inhibitors</topic><topic>Receptors, N-Methyl-D-Aspartate - metabolism</topic><topic>Stem cells</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Ohno, Masuo</creatorcontrib><creatorcontrib>Frankland, Paul W.</creatorcontrib><creatorcontrib>Chen, Adele P.</creatorcontrib><creatorcontrib>Costa, Rui M.</creatorcontrib><creatorcontrib>Silva, Alcino J.</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Gale In Context: Science</collection><collection>ProQuest Central (Corporate)</collection><collection>Animal Behavior Abstracts</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Chemoreception Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Toxicology Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>Psychology Database (Alumni)</collection><collection>ProQuest Pharma Collection</collection><collection>Technology Research Database</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Natural Science Collection</collection><collection>Environmental Sciences and Pollution Management</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Engineering Research Database</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>ProQuest Biological Science Collection</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>ProQuest Psychology</collection><collection>Biological Science Database</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>ProQuest One Psychology</collection><collection>ProQuest Central Basic</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Nature neuroscience</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Ohno, Masuo</au><au>Frankland, Paul W.</au><au>Chen, Adele P.</au><au>Costa, Rui M.</au><au>Silva, Alcino J.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Inducible, pharmacogenetic approaches to the study of learning and memory</atitle><jtitle>Nature neuroscience</jtitle><stitle>Nat Neurosci</stitle><addtitle>Nat Neurosci</addtitle><date>2001-12-01</date><risdate>2001</risdate><volume>4</volume><issue>12</issue><spage>1238</spage><epage>1243</epage><pages>1238-1243</pages><issn>1097-6256</issn><eissn>1546-1726</eissn><coden>NANEFN</coden><abstract>Here we introduce a strategy in which pharmacology is used to induce the effects of recessive mutations. For example, mice heterozygous for a null mutation of the K-
ras
gene (K-
ras
+/−
) show normal hippocampal mitogen-activated protein kinase (MAPK) activation, long-term potentiation (LTP) and contextual conditioning. However, a dose of a mitogen-activated/extracellular-signal-regulated kinase (MEK) inhibitor, ineffective in wild-type controls, blocks MAPK activation, LTP and contextual learning in K-
ras
+/−
mutants. These indicate that K-Ras/MEK/MAPK signaling is critical in synaptic and behavioral plasticity. A subthreshold dose of NMDA receptor antagonists triggered a contextual learning deficit in mice heterozygous for a point mutation (T286A) in the αCaMKII gene, but not in K-
ras
+/−
mutants, demonstrating the specificity of the synergistic interaction between the MEK inhibitor and the K-
ras
+/−
mutation. This pharmacogenetic approach combines the high temporal specificity that pharmacological manipulations offer, with the molecular specificity of genetic disruptions.</abstract><cop>New York</cop><pub>Nature Publishing Group US</pub><pmid>11713472</pmid><doi>10.1038/nn771</doi><tpages>6</tpages></addata></record> |
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| issn | 1097-6256 1546-1726 |
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| source | MEDLINE; Nature; SpringerLink Journals - AutoHoldings |
| subjects | aCaMKII gene Animal Genetics and Genomics Animals Avoidance Learning - drug effects Avoidance Learning - physiology Axons - drug effects Axons - metabolism Behavioral Sciences Biological Techniques Biomedical and Life Sciences Biomedicine Calcium-Calmodulin-Dependent Protein Kinase Type 2 Calcium-Calmodulin-Dependent Protein Kinases - deficiency Calcium-Calmodulin-Dependent Protein Kinases - genetics Conditioning (Psychology) - drug effects Conditioning (Psychology) - physiology Electric Stimulation Enzyme Inhibitors - pharmacology Excitatory Amino Acid Antagonists - pharmacology Excitatory Postsynaptic Potentials - drug effects Excitatory Postsynaptic Potentials - physiology Fear - drug effects Fear - physiology Female Gene targeting Genes, ras - drug effects Genes, ras - physiology Genetic aspects Heterozygote Hippocampus - drug effects Hippocampus - metabolism K-Ras gene Kinases Learning Learning - drug effects Learning - physiology Long-Term Potentiation - drug effects Long-Term Potentiation - physiology Male MAP Kinase Kinase 1 MAP Kinase Signaling System - drug effects MAP Kinase Signaling System - physiology Memory Memory - drug effects Memory - physiology Mice Mice, Knockout Mitogen-Activated Protein Kinase Kinases - antagonists & inhibitors Mitogen-Activated Protein Kinase Kinases - metabolism Mitogen-Activated Protein Kinases - antagonists & inhibitors Mitogen-Activated Protein Kinases - metabolism Mutation Mutation - drug effects Mutation - physiology Neurobiology Neurosciences Pharmacogenetics Phosphorylation Physiological aspects Protein-Serine-Threonine Kinases - antagonists & inhibitors Protein-Serine-Threonine Kinases - metabolism Proteins Publishing Receptors, N-Methyl-D-Aspartate - antagonists & inhibitors Receptors, N-Methyl-D-Aspartate - metabolism Stem cells |
| title | Inducible, pharmacogenetic approaches to the study of learning and memory |
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