Contribution of CRF and 5-HT in the anterodorsal BNST to phasic and sustained fear in freely behaving mice


Rodent data suggest that short-lasting (phasic) fear responses rely on the central amygdala, whereas more long-lasting (sustained) fear responses critically depend on the bed nucleus of the stria terminalis (BNST). This project is based on the hypothesis that sustained fear can be decisively modulated by corticotropin releasing factor (CRF) and serotonin (5-HT) in the antero-dorsal BNST (sdBNST) (s. Figure).  The overall aim of the project is to elucidate key mechanisms in the adBNST underlying phasic/sustained fear with special focus on the contribution of CRF1- and 5-HT receptor-mediated processes. To address this project, we are going to use pharmacological and optogenetical approaches in combination with established fear conditioning protocols in the phasic/sustained fear mouse model.

Schematic drawing illustrating hypothetical contribution of CRF- and 5-HT-mediated processes in the adBNST to phasic and sustained fear modulation after fear conditioning. Dashed lines indicate inhibitory synaptic connections, solid black arrows excitatory. CeA: central amygdala, BLA: basolateral amygdala, adBNST: anterodorsal part of bed nucleus of stria terminalis, DRN: dorsal raphe nucleus. (modified from Hammack et al., 2009; Guo and Rainnie, 2010).