Aging redistributes medial prefrontal neuronal excitability and impedes extinction of trace fear conditioning
Abstract Cognitive flexibility is critical for survival and reflects the malleability of the central nervous system (CNS) in response to changing environmental demands. Normal aging results in difficulties modifying established behaviors, which may involve medial prefrontal cortex (mPFC) dysfunction...
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| Veröffentlicht in: | Neurobiology of aging 2012-08, Vol.33 (8), p.1744-1757 |
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| container_title | Neurobiology of aging |
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| creator | Kaczorowski, Catherine C Davis, Scott J Moyer, James R |
| description | Abstract Cognitive flexibility is critical for survival and reflects the malleability of the central nervous system (CNS) in response to changing environmental demands. Normal aging results in difficulties modifying established behaviors, which may involve medial prefrontal cortex (mPFC) dysfunction. Using extinction of conditioned fear in rats to assay cognitive flexibility, we demonstrate that extinction deficits reminiscent of mPFC dysfunction first appear during middle age, in the absence of hippocampus-dependent context deficits. Emergence of aging-related extinction deficits paralleled a redistribution of neuronal excitability across two critical mPFC regions via two distinct mechanisms. First, excitability decreased in regular spiking neurons of infralimbic-mPFC (IL), a region whose activity is required for extinction. Second, excitability increased in burst spiking neurons of prelimbic-mPFC (PL), a region whose activity hinders extinction. Experiments using synaptic blockers revealed that these aging-related differences were intrinsic. Thus, changes in IL and PL intrinsic excitability may contribute to cognitive flexibility impairments observed during normal aging. |
| doi_str_mv | 10.1016/j.neurobiolaging.2011.03.020 |
| format | Article |
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Normal aging results in difficulties modifying established behaviors, which may involve medial prefrontal cortex (mPFC) dysfunction. Using extinction of conditioned fear in rats to assay cognitive flexibility, we demonstrate that extinction deficits reminiscent of mPFC dysfunction first appear during middle age, in the absence of hippocampus-dependent context deficits. Emergence of aging-related extinction deficits paralleled a redistribution of neuronal excitability across two critical mPFC regions via two distinct mechanisms. First, excitability decreased in regular spiking neurons of infralimbic-mPFC (IL), a region whose activity is required for extinction. Second, excitability increased in burst spiking neurons of prelimbic-mPFC (PL), a region whose activity hinders extinction. Experiments using synaptic blockers revealed that these aging-related differences were intrinsic. Thus, changes in IL and PL intrinsic excitability may contribute to cognitive flexibility impairments observed during normal aging.</description><identifier>ISSN: 0197-4580</identifier><identifier>EISSN: 1558-1497</identifier><identifier>DOI: 10.1016/j.neurobiolaging.2011.03.020</identifier><identifier>PMID: 21531046</identifier><language>eng</language><publisher>United States: Elsevier Inc</publisher><subject>Aging ; Aging - physiology ; Animals ; Burst spiking ; Central nervous system ; Cognitive ability ; Cognitive flexibility ; Conditioning, Classical - physiology ; Cortex (prefrontal) ; Excitability ; Extinction ; Extinction, Psychological - physiology ; Fear - physiology ; Fear conditioning ; Firing pattern ; Infralimbic ; Internal Medicine ; Intrinsic excitability ; Male ; Nerve Net - physiology ; Nervous system ; Neurology ; Neurons ; Prefrontal Cortex - physiology ; Prelimbic ; Rats ; Rats, Inbred F344 ; Regular spiking ; Trace fear conditioning</subject><ispartof>Neurobiology of aging, 2012-08, Vol.33 (8), p.1744-1757</ispartof><rights>Elsevier Inc.</rights><rights>2012 Elsevier Inc.</rights><rights>Copyright © 2012 Elsevier Inc. All rights reserved.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c474t-6623fe73c985be9ceec004e229c4da7edc4cbbda47a519c9767342c5ebe482763</citedby><cites>FETCH-LOGICAL-c474t-6623fe73c985be9ceec004e229c4da7edc4cbbda47a519c9767342c5ebe482763</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.neurobiolaging.2011.03.020$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,780,784,3550,27924,27925,45995</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/21531046$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Kaczorowski, Catherine C</creatorcontrib><creatorcontrib>Davis, Scott J</creatorcontrib><creatorcontrib>Moyer, James R</creatorcontrib><title>Aging redistributes medial prefrontal neuronal excitability and impedes extinction of trace fear conditioning</title><title>Neurobiology of aging</title><addtitle>Neurobiol Aging</addtitle><description>Abstract Cognitive flexibility is critical for survival and reflects the malleability of the central nervous system (CNS) in response to changing environmental demands. Normal aging results in difficulties modifying established behaviors, which may involve medial prefrontal cortex (mPFC) dysfunction. Using extinction of conditioned fear in rats to assay cognitive flexibility, we demonstrate that extinction deficits reminiscent of mPFC dysfunction first appear during middle age, in the absence of hippocampus-dependent context deficits. Emergence of aging-related extinction deficits paralleled a redistribution of neuronal excitability across two critical mPFC regions via two distinct mechanisms. First, excitability decreased in regular spiking neurons of infralimbic-mPFC (IL), a region whose activity is required for extinction. Second, excitability increased in burst spiking neurons of prelimbic-mPFC (PL), a region whose activity hinders extinction. Experiments using synaptic blockers revealed that these aging-related differences were intrinsic. Thus, changes in IL and PL intrinsic excitability may contribute to cognitive flexibility impairments observed during normal aging.</description><subject>Aging</subject><subject>Aging - physiology</subject><subject>Animals</subject><subject>Burst spiking</subject><subject>Central nervous system</subject><subject>Cognitive ability</subject><subject>Cognitive flexibility</subject><subject>Conditioning, Classical - physiology</subject><subject>Cortex (prefrontal)</subject><subject>Excitability</subject><subject>Extinction</subject><subject>Extinction, Psychological - physiology</subject><subject>Fear - physiology</subject><subject>Fear conditioning</subject><subject>Firing pattern</subject><subject>Infralimbic</subject><subject>Internal Medicine</subject><subject>Intrinsic excitability</subject><subject>Male</subject><subject>Nerve Net - physiology</subject><subject>Nervous system</subject><subject>Neurology</subject><subject>Neurons</subject><subject>Prefrontal Cortex - physiology</subject><subject>Prelimbic</subject><subject>Rats</subject><subject>Rats, Inbred F344</subject><subject>Regular spiking</subject><subject>Trace fear conditioning</subject><issn>0197-4580</issn><issn>1558-1497</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2012</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqNUk1v1DAQtRCILoW_gHLgwCVh7DhxIiGkqqK0UiUOwNlyJpPKS2IvtoO6_x6HLUhw6slj633I7w1jbzhUHHj7bl85WoMfrJ_NnXV3lQDOK6grEPCE7XjTdCWXvXrKdsB7VcqmgzP2IsY9ACip2ufsTPCm5iDbHVsuNo0i0GhjCnZYE8ViyTczF4dAU_Au5fG3pcsD3aNNZrCzTcfCuLGwy4HGzKH7ZB0m613hpyIFg1RMZEKB3o12e88-L9mzycyRXj2c5-zb1cevl9fl7edPN5cXtyVKJVPZtqKeSNXYd81APRIhgCQhepSjUTSixGEYjVSm4T32qlW1FNjQQLITqq3P2duT7iH4HyvFpBcbkebZOPJr1Bxq2XEODX8EVGTvTnRdhr4_QTH4GHM4-hDsYsIxg_TWjd7rf7vRWzcaap1FMv31g9M65IT_kv-UkQFXJwDlaH5aCjqiJYe5jUCY9OjtY50-_CeEs3UWzfydjhT3fg25y_w3HYUG_WXbk21NciIAvRL1L3GowCU</recordid><startdate>20120801</startdate><enddate>20120801</enddate><creator>Kaczorowski, Catherine C</creator><creator>Davis, Scott J</creator><creator>Moyer, James R</creator><general>Elsevier Inc</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>7X8</scope><scope>7TK</scope></search><sort><creationdate>20120801</creationdate><title>Aging redistributes medial prefrontal neuronal excitability and impedes extinction of trace fear conditioning</title><author>Kaczorowski, Catherine C ; Davis, Scott J ; Moyer, James R</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c474t-6623fe73c985be9ceec004e229c4da7edc4cbbda47a519c9767342c5ebe482763</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2012</creationdate><topic>Aging</topic><topic>Aging - physiology</topic><topic>Animals</topic><topic>Burst spiking</topic><topic>Central nervous system</topic><topic>Cognitive ability</topic><topic>Cognitive flexibility</topic><topic>Conditioning, Classical - physiology</topic><topic>Cortex (prefrontal)</topic><topic>Excitability</topic><topic>Extinction</topic><topic>Extinction, Psychological - physiology</topic><topic>Fear - physiology</topic><topic>Fear conditioning</topic><topic>Firing pattern</topic><topic>Infralimbic</topic><topic>Internal Medicine</topic><topic>Intrinsic excitability</topic><topic>Male</topic><topic>Nerve Net - physiology</topic><topic>Nervous system</topic><topic>Neurology</topic><topic>Neurons</topic><topic>Prefrontal Cortex - physiology</topic><topic>Prelimbic</topic><topic>Rats</topic><topic>Rats, Inbred F344</topic><topic>Regular spiking</topic><topic>Trace fear conditioning</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Kaczorowski, Catherine C</creatorcontrib><creatorcontrib>Davis, Scott J</creatorcontrib><creatorcontrib>Moyer, James R</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>Neurosciences Abstracts</collection><jtitle>Neurobiology of aging</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Kaczorowski, Catherine C</au><au>Davis, Scott J</au><au>Moyer, James R</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Aging redistributes medial prefrontal neuronal excitability and impedes extinction of trace fear conditioning</atitle><jtitle>Neurobiology of aging</jtitle><addtitle>Neurobiol Aging</addtitle><date>2012-08-01</date><risdate>2012</risdate><volume>33</volume><issue>8</issue><spage>1744</spage><epage>1757</epage><pages>1744-1757</pages><issn>0197-4580</issn><eissn>1558-1497</eissn><abstract>Abstract Cognitive flexibility is critical for survival and reflects the malleability of the central nervous system (CNS) in response to changing environmental demands. 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| subjects | Aging Aging - physiology Animals Burst spiking Central nervous system Cognitive ability Cognitive flexibility Conditioning, Classical - physiology Cortex (prefrontal) Excitability Extinction Extinction, Psychological - physiology Fear - physiology Fear conditioning Firing pattern Infralimbic Internal Medicine Intrinsic excitability Male Nerve Net - physiology Nervous system Neurology Neurons Prefrontal Cortex - physiology Prelimbic Rats Rats, Inbred F344 Regular spiking Trace fear conditioning |
| title | Aging redistributes medial prefrontal neuronal excitability and impedes extinction of trace fear conditioning |
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