Type of Thesis
Molecular, Cellular, & Developmental Biology
Dr. Christopher A. Lowry
Exposure to stressors triggers the release of corticotropin-releasing hormone (Crh), which mediates the physiological and behavioral stress response through activation of corticotropin-releasing hormone receptor type-1 and 2 (CRHR2). Crhr2 is a G protein-coupled-receptor found on the surface of cells across the brain, including serotonergic neurons in the dorsal raphe nucleus (DRN). Studies performing global knockout of Crhr2 show anxiolytic effects, but cannot attribute these effects to changes in Crh signaling in specific neural systems. This study utilized a Pet1-driven Cre-mediated knockout of Crhr2 from serotonergic neurons to elucidate the effects of Crh signaling on serotonergic neurons in the DRN. To measure the impact of deletion of Crhr2 in serotonergic neurons on genes that are important modulators of serotonergic signaling, we measured mRNA expression levels of serotonin transporter gene slc6a4. Using in situ hybridization histochemistry we analyzed slc6a4 mRNA expression across subregions of the DRN and median raphe nucleus. We found a localized decrease in the expression levels of slc6a4 mRNA in the mid-rostrocaudal region of the ventral dorsal raphe nucleus (DRV). A decrease in slc6a4 mRNA, if representative of levels of serotonin transporter protein expression and trafficking to the plasma membrane, would suggest an increase in the serotonergic signaling of brain regions innervated by this population of neurons. Crhr2 primarily has an excitatory role in neuronal signaling and deletion of Crhr2 would remove an important excitatory input to these neurons. Decreased slc6a4 mRNA expression could implicate a possible compensatory role for the loss of excitatory Crhr2 in the mid-rostrocaudal DRV.
Malzbender, Joseph H., "Conditional Knockout of Crhr2 in Serotonergic Neurons Decreases the Expression of slc6a4 mRNA in the Ventral Dorsal Raphe Nucleus" (2016). Undergraduate Honors Theses. 1089.