Type of Thesis
Stressful events have been shown to increase noradrenergic signaling in key limbic areas, such as the hypothalamus, the amygdala, and the locus coeruleus. The basolateral amygdaloid nucleus (BL) is known to play a central role in the mediation of fear and anxiety responses to potentially harmful stimuli. In order to study the effects of altered noradrenergic signaling in the BL on downstream projection targets, we preferentially overexpressed or knocked-down transcription of microRNA-19b (miR-19b) in order to selectively alter the expression of the β1-adrenergic receptor (Adrb1) in the BL of mice. Lentiviral constructs were injected directly into the BL of experimental subjects using stereotaxic surgery, after which mice underwent behavioral testing to assess for anxiety- and fear-like behavior. Mice were sacrificed 52 days following infection with lentiviral vectors. Key brain areas downstream of the BL were microdissected and analyzed using high performance liquid chromatography with electrochemical detection for norepinephrine and 3-methoxy-4-hydroxyphenylglycol concentrations. We observed altered noradrenergic metabolism in brain structures intimately involved in the regulation of anxiety and fear responses, such as the hippocampus and the hypothalamus. Briefly, we saw decreases in noradrenergic metabolism in the paraventricular nucleus of the hypothalamus and the dorsal hippocampus for miR-19b OE, and conversely, increases in noradrenergic metabolism in these same brain regions for miR-19b KD. These data suggest that miR-19b, acting within the BL to modulate Adrb1 expression, can alter noradrenergic metabolism in downstream limbic structures, likely by affecting presynaptic modulation of glutamatergic outputs from the BL to target structures. Our data will hopefully guide further study into noradrenergic limbic circuitry, and thus may provide a deeper understanding of anxiety and affective disorders that plague today’s society.
Fields, Brandon, "The effects of microRNA-19b overexpression and knockdown in the basolateral amygdaloid nucleus on noradrenergic metabolism" (2014). Undergraduate Honors Theses. 90.