Bernabe CS, Caliman IF, Abreu ARR, Shekhar A, Johnson PL (2016) A unique subdivision of serotonergic neurons in the dorsal raphe nucleus projects to the basolateral amygdala complex to enhance fear-conditioned behaviors. Neuroscience 2016 Abstracts 74.23 / GGG14. Society for Neuroscience, San Diego, CA.
Summary: The basolateral and lateral amygdala nuclei complex (BLC) is implicated in a number of emotional responses including fear and anxiety. Previous studies have shown that increased serotonin release in the BLC enhances fear conditioned behaviors, and we recently demonstrated that pharmacologically depleting serotonin in the BLC using 5,7-dihydroxytryptamine (5,7,DHT) injections disrupted fear conditioned behaviors. In 2005 Abrams and colleagues determined that there were robust BLC projections that originate from the midline dorsal (DRD) and ventral (DRV) subdivisions of the dorsal raphe nucleus (DRN), but it was not determined that they were serotonergic. Here we injected a saporin (SAP) toxin coupled to a serotonin transporter (SERT) into the BLC to selectively lesion local serotonergic fibers which replicated disrupted fear conditioning behaviors that was observed in the BLC 5,7DHT study. Since the SERT-SAP can retrogradely lesion the associated cell bodies (Shen et al., 2007) via fast retrograde microtubule associated transport, we also injected the retrograde tracer cholera toxin B (CtB) into the BLC via same the cannula that SERT-SAP was injected. This was done to not only verify loss of serotonergic neurons in DRN subdivisions, but also to specifically verify BLC projecting serotonergic neurons. We later used immunohistochemistry (IHC) to detect SERT in the BLC and observed a 90% decrease in local SERT-immunoreactive fibers. We also verified that almost all CtB-immunoreactive BLC projecting neurons in DRN were also positive for tryptophan hydroxylase (TPH: a serotonergic specific enzyme). We further determined that BLC projecting neurons immunoreactive for both CtB and TPH were primarily located within the midline DRD and DRV divisions of the DRN, and not in the lateral wing (DRVL) divisions of DRN. Regardless of location, the SERT-SAP group had 72% to 74% less CtB/TPH-double immunoreactive neurons than control-SAP group. These data elucidate the roles of serotonergic networks in the pathophysiology of fear, and especially focus on the origins of these pathways as a way to identify potential novel therapeutic targets.
Related Products: Anti-SERT-SAP (Cat. #IT-23)