Undergraduate Honors Thesis
Conditional knockout of Crhr2 in serotonergic neurons decreases the expression of htr1a in the dorsal raphe nucleus Public Deposited
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Stressful environmental cues contribute to the etiology of anxiety and affective disorders. Stressors trigger the release of corticotropin-releasign hormone (Crh), which contributes to control of anxiety-related behaviors through actions at the receptors Crhr1 and Crhr2 in the dorsal and median raphe nuclei (DR and MnR). Previous studies of Crhr2 effects on anxiety-like behavior entailed nonspecific, organism-wide knock out of Crhr2, potentially affecting signaling in the many peripheral and central nervous system tissues expressing Crhr2. Consequently, anxiolytic effects resulting from the nonspecific loss of Crhr2 expression throughout the CNS could not be attributed to changes in Crh-mediated signaling in the DR or MnR. In this study, we used a Cre-loxP knockout system with a Pet1-driven Cre recombinase in mice to generate a conditional Crhr2 knockout specific to serotonergic (5-HT) neurons (KOR2-5HT), allowing for a more precise characterization of Crhr2 signaling on DR and MnR function. In order to evaluate potential effects of Crhr2 deletion on 5-HT signaling in these nuclei, we measured gene expression of the inhibitory autoreceptor Htr1a, which modulates both neuronal excitation and firing rate. In situ hybridization histochemical analysis of brainstem tissue revealed a decrease in of htr1a transcripts in all subdivisions of the DR but not in the MnR in KOR2-5HT mice. Given that Crhr2 couples primarily to excitatory G proteins, this finding suggests that downregulation of inhibitory Htr1a receptors compensates for the loss of excitatory Crhr2 signaling in the DR in order to preserve normal firing rates, and that this mechanism is less pertinent to serotonergic signaling in the MnR.
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- 2015-01-01
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- 2020-01-28
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conditionalKnockoutOfCrhr2InSerotonergicNeuronsDecreasesT.pdf | 2019-12-02 | Public | Download |