Studies on the mode of CRF action in the optic tectum of the African Clawed Frog, Xenopus laevis

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Stress and anxiety induce the expression of defensive behaviors, which help animals escape from the source of danger or motivational conflict. An important brain area for coordinating the behavioral response to visual threats is the superior colliculus of the brain, an area involved in subconscious visual detection and response. Previous work in our lab showed that optic tectum (OT), the homolog of superior colliculus in non-mammalian vertebrates, contributes to decision making on predator avoidance/prey capture tradeoffs. The neuropeptide corticotropin releasing factor (CRF) modulates discrete aspects of prey capture and predator avoidance, but the mechanisms underlying this modulation are unknown. This dissertation consists of my research exploring two potential pathways that can communicate with CRF signaling pathway in OT. In the third and the fourth chapter of my dissertation, we tested the hypothesis that CRF signaling pathway and GABA signaling pathway communicate in OT by modulating Ca2+ flux. The third chapter using dual-labeling immunofluorescence and laser confocal microscopy successfully showed interactions between CRF neurons and GABAergic neurons, which provided neuroanatomical evidence for the direct GABA regulation on CRF signaling pathway. The fourth chapter used the fluorescent Ca2+ marker to show the real-time Ca2+ concentration in response to CRF, but failed to prove the Ca2+ flux was able to be regulated by CRF or GABA. The last chapter used microscopy, RIA and LCMS to explore a feedback loop from HPA axis to CRF neurons in OT and validate a noninvasive assay measuring predator-induced physiological changes in juvenile Xenopus laevis. We found neuroanatomical evidence for HPA axis feedback on CRF neurons in OT and a noninvasive assay measuring stressor-induced corticosterone in water samples, whose receptors were colocalized with CRF. This indicated a potential feedback loop from the downstream neuroendocrinal response to the upstream visual stressor perception. These experiments will not only help understand the complexity of the communication between GABA and CRF signaling pathway in OT, but also provide new pointcuts on studying the feedback regulation of CRF-mediated visual stressor processing in OT.

Embargo status: Restricted until 01/2030. To request the author grant access, click on the PDF link to the left.

stress, Gamma-aminobutyric acid (GABA), Corticotropin-releasing factor (CRF), optic tectum, xenopus, corticosterone