dc.creator | Jacobs, Michelle Marie | |
dc.date.accessioned | 2020-08-21T20:56:33Z | |
dc.date.available | 2011-01-20 | |
dc.date.issued | 2009-01-20 | |
dc.identifier.uri | https://etd.library.vanderbilt.edu/etd-01192009-142814 | |
dc.identifier.uri | http://hdl.handle.net/1803/10453 | |
dc.description.abstract | RNA transcripts encoding the 2C-subtype of the serotonin (5HT2C) receptor are modified by adenosine-to-inosine editing events to generate as many as twenty-four 5HT2C receptor protein isoforms. These modified receptors are expressed in a region-specific manner in the central nervous system (CNS) and demonstrate differences in their constitutive activity and efficacy to interact with specific G-proteins. To determine the physiologic relevance of 5HT2C RNA editing, I generated mutant mice solely expressing the non-edited isoform (5HT2C-INI) of the receptor. Heterozygous mutant dams display profound behavioral deficits in maternal care including poor nest formation and altered pup retrieval that affect growth and anxiety-related behavior in both wild-type and mutant offspring. Treatment with a selective 5HT2C inverse agonist rescues deficits in pup retrieval, indicating that altered 5HT2C signaling underlies the observed alterations in maternal behavior. These studies not only indicate a role for 5HT2C signaling in maternal care, but also demonstrate the importance of normal patterns of 5HT2C RNA editing in vivo. | |
dc.format.mimetype | application/pdf | |
dc.subject | G-protein coupling | |
dc.subject | adaptive compensation | |
dc.subject | RNA editing | |
dc.subject | constitutive activity | |
dc.subject | Serotonin -- Receptors | |
dc.subject | Serotonin -- Physiological effect | |
dc.subject | Parental behavior in animals | |
dc.title | Altered Isoform Expression of the Serotonin 2C Receptor Disrupts Normal Maternal Care | |
dc.type | dissertation | |
dc.contributor.committeeMember | Randy Blakely | |
dc.contributor.committeeMember | Elaine Sanders-Bush | |
dc.contributor.committeeMember | Maureen Gannon | |
dc.contributor.committeeMember | Ronald Emeson | |
dc.type.material | text | |
thesis.degree.name | PHD | |
thesis.degree.level | dissertation | |
thesis.degree.discipline | Neuroscience | |
thesis.degree.grantor | Vanderbilt University | |
local.embargo.terms | 2011-01-20 | |
local.embargo.lift | 2011-01-20 | |
dc.contributor.committeeChair | Pat Levitt | |