Phospholipase C beta 4 in the medial septum controls cholinergic theta oscillations and anxiety behaviors
Anxiety is among the most prevalent and costly diseases of the CNS, but its underlying mechanisms are not fully understood. Although attenuated theta rhythms have been observed in human subjects with increased anxiety, no study has been done on the possible physiological link between these two manif...
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| Veröffentlicht in: | The Journal of neuroscience 2009-12, Vol.29 (49), p.15375-15385 |
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| creator | Shin, Jonghan Gireesh, Gangadharan Kim, Seong-Wook Kim, Duk-Soo Lee, Sukyung Kim, Yeon-Soo Watanabe, Masahiko Shin, Hee-Sup |
| description | Anxiety is among the most prevalent and costly diseases of the CNS, but its underlying mechanisms are not fully understood. Although attenuated theta rhythms have been observed in human subjects with increased anxiety, no study has been done on the possible physiological link between these two manifestations. We found that the mutant mouse for phospholipase C beta 4 (PLC-beta 4(-/-)) showed attenuated theta rhythm and increased anxiety, presenting the first animal model for the human condition. PLC-beta 4 is abundantly expressed in the medial septum, a region implicated in anxiety behavior. RNA interference-mediated PLC-beta 4 knockdown in the medial septum produced a phenotype similar to that of PLC-beta 4(-/-) mice. Furthermore, increasing cholinergic signaling by administering an acetylcholinesterase inhibitor cured the anomalies in both cholinergic theta rhythm and anxiety behavior observed in PLC-beta 4(-/-) mice. These findings suggest that (1) PLC-beta 4 in the medial septum is involved in controlling cholinergic theta oscillation and (2) cholinergic theta rhythm plays a critical role in suppressing anxiety. We propose that defining the cholinergic theta rhythm profile may provide guidance in subtyping anxiety disorders in humans for more effective diagnosis and treatments. |
| doi_str_mv | 10.1523/JNEUROSCI.3126-09.2009 |
| format | Article |
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Although attenuated theta rhythms have been observed in human subjects with increased anxiety, no study has been done on the possible physiological link between these two manifestations. We found that the mutant mouse for phospholipase C beta 4 (PLC-beta 4(-/-)) showed attenuated theta rhythm and increased anxiety, presenting the first animal model for the human condition. PLC-beta 4 is abundantly expressed in the medial septum, a region implicated in anxiety behavior. RNA interference-mediated PLC-beta 4 knockdown in the medial septum produced a phenotype similar to that of PLC-beta 4(-/-) mice. Furthermore, increasing cholinergic signaling by administering an acetylcholinesterase inhibitor cured the anomalies in both cholinergic theta rhythm and anxiety behavior observed in PLC-beta 4(-/-) mice. These findings suggest that (1) PLC-beta 4 in the medial septum is involved in controlling cholinergic theta oscillation and (2) cholinergic theta rhythm plays a critical role in suppressing anxiety. We propose that defining the cholinergic theta rhythm profile may provide guidance in subtyping anxiety disorders in humans for more effective diagnosis and treatments.</description><identifier>EISSN: 1529-2401</identifier><identifier>DOI: 10.1523/JNEUROSCI.3126-09.2009</identifier><identifier>PMID: 20007462</identifier><language>eng</language><publisher>United States</publisher><subject>Acetylcholine - metabolism ; Animals ; Anxiety - drug therapy ; Anxiety - physiopathology ; Cholinesterase Inhibitors - pharmacology ; Electroencephalography ; Gene Knockdown Techniques ; Gene Silencing ; Immunohistochemistry ; Inverted Repeat Sequences ; Mice ; Mice, Knockout ; Neurons - drug effects ; Neurons - physiology ; Neuropsychological Tests ; Phenylcarbamates - pharmacology ; Phospholipase C beta - genetics ; Phospholipase C beta - metabolism ; Rivastigmine ; RNA Interference ; Septum of Brain - drug effects ; Septum of Brain - physiopathology ; Theta Rhythm</subject><ispartof>The Journal of neuroscience, 2009-12, Vol.29 (49), p.15375-15385</ispartof><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27923,27924</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/20007462$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Shin, Jonghan</creatorcontrib><creatorcontrib>Gireesh, Gangadharan</creatorcontrib><creatorcontrib>Kim, Seong-Wook</creatorcontrib><creatorcontrib>Kim, Duk-Soo</creatorcontrib><creatorcontrib>Lee, Sukyung</creatorcontrib><creatorcontrib>Kim, Yeon-Soo</creatorcontrib><creatorcontrib>Watanabe, Masahiko</creatorcontrib><creatorcontrib>Shin, Hee-Sup</creatorcontrib><title>Phospholipase C beta 4 in the medial septum controls cholinergic theta oscillations and anxiety behaviors</title><title>The Journal of neuroscience</title><addtitle>J Neurosci</addtitle><description>Anxiety is among the most prevalent and costly diseases of the CNS, but its underlying mechanisms are not fully understood. Although attenuated theta rhythms have been observed in human subjects with increased anxiety, no study has been done on the possible physiological link between these two manifestations. We found that the mutant mouse for phospholipase C beta 4 (PLC-beta 4(-/-)) showed attenuated theta rhythm and increased anxiety, presenting the first animal model for the human condition. PLC-beta 4 is abundantly expressed in the medial septum, a region implicated in anxiety behavior. RNA interference-mediated PLC-beta 4 knockdown in the medial septum produced a phenotype similar to that of PLC-beta 4(-/-) mice. Furthermore, increasing cholinergic signaling by administering an acetylcholinesterase inhibitor cured the anomalies in both cholinergic theta rhythm and anxiety behavior observed in PLC-beta 4(-/-) mice. These findings suggest that (1) PLC-beta 4 in the medial septum is involved in controlling cholinergic theta oscillation and (2) cholinergic theta rhythm plays a critical role in suppressing anxiety. We propose that defining the cholinergic theta rhythm profile may provide guidance in subtyping anxiety disorders in humans for more effective diagnosis and treatments.</description><subject>Acetylcholine - metabolism</subject><subject>Animals</subject><subject>Anxiety - drug therapy</subject><subject>Anxiety - physiopathology</subject><subject>Cholinesterase Inhibitors - pharmacology</subject><subject>Electroencephalography</subject><subject>Gene Knockdown Techniques</subject><subject>Gene Silencing</subject><subject>Immunohistochemistry</subject><subject>Inverted Repeat Sequences</subject><subject>Mice</subject><subject>Mice, Knockout</subject><subject>Neurons - drug effects</subject><subject>Neurons - physiology</subject><subject>Neuropsychological Tests</subject><subject>Phenylcarbamates - pharmacology</subject><subject>Phospholipase C beta - genetics</subject><subject>Phospholipase C beta - metabolism</subject><subject>Rivastigmine</subject><subject>RNA Interference</subject><subject>Septum of Brain - drug effects</subject><subject>Septum of Brain - physiopathology</subject><subject>Theta Rhythm</subject><issn>1529-2401</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2009</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNo1kEFPwzAMhSMkxMbgL0y5cepwnLRpj6gaMDQxBOxcpW1Kg9qmNCli_55OjINlS_7e07MJWTJYsRD57dPzev-6e0s3K84wCiBZIUByRubTNglQAJuRS-c-AUACkxdkhsdRRDgn5qW2rq9tY3rlNE1prr2igpqO-lrTVpdGNdTp3o8tLWznB9s4WhwFnR4-THHEJoV1hWka5Y3tHFVdOdWP0f4w-dXq29jBXZHzSjVOX5_6guzv1-_pY7DdPWzSu23QMwE-EFFccOAVyIghj5EhVgiRAkSuI80QcimKsNIVihDjqoyTJFcl56GGHOKcL8jNn28_2K9RO5-1xhV6CtdpO7pMcsESKeN4IpcncsynQ7N-MK0aDtn_d_gvScNnCA</recordid><startdate>20091209</startdate><enddate>20091209</enddate><creator>Shin, Jonghan</creator><creator>Gireesh, Gangadharan</creator><creator>Kim, Seong-Wook</creator><creator>Kim, Duk-Soo</creator><creator>Lee, Sukyung</creator><creator>Kim, Yeon-Soo</creator><creator>Watanabe, Masahiko</creator><creator>Shin, Hee-Sup</creator><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>7X8</scope></search><sort><creationdate>20091209</creationdate><title>Phospholipase C beta 4 in the medial septum controls cholinergic theta oscillations and anxiety behaviors</title><author>Shin, Jonghan ; 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Although attenuated theta rhythms have been observed in human subjects with increased anxiety, no study has been done on the possible physiological link between these two manifestations. We found that the mutant mouse for phospholipase C beta 4 (PLC-beta 4(-/-)) showed attenuated theta rhythm and increased anxiety, presenting the first animal model for the human condition. PLC-beta 4 is abundantly expressed in the medial septum, a region implicated in anxiety behavior. RNA interference-mediated PLC-beta 4 knockdown in the medial septum produced a phenotype similar to that of PLC-beta 4(-/-) mice. Furthermore, increasing cholinergic signaling by administering an acetylcholinesterase inhibitor cured the anomalies in both cholinergic theta rhythm and anxiety behavior observed in PLC-beta 4(-/-) mice. These findings suggest that (1) PLC-beta 4 in the medial septum is involved in controlling cholinergic theta oscillation and (2) cholinergic theta rhythm plays a critical role in suppressing anxiety. We propose that defining the cholinergic theta rhythm profile may provide guidance in subtyping anxiety disorders in humans for more effective diagnosis and treatments.</abstract><cop>United States</cop><pmid>20007462</pmid><doi>10.1523/JNEUROSCI.3126-09.2009</doi><tpages>11</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Acetylcholine - metabolism Animals Anxiety - drug therapy Anxiety - physiopathology Cholinesterase Inhibitors - pharmacology Electroencephalography Gene Knockdown Techniques Gene Silencing Immunohistochemistry Inverted Repeat Sequences Mice Mice, Knockout Neurons - drug effects Neurons - physiology Neuropsychological Tests Phenylcarbamates - pharmacology Phospholipase C beta - genetics Phospholipase C beta - metabolism Rivastigmine RNA Interference Septum of Brain - drug effects Septum of Brain - physiopathology Theta Rhythm |
| title | Phospholipase C beta 4 in the medial septum controls cholinergic theta oscillations and anxiety behaviors |
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