Dissecting The Functional Heterogeneity Of Serotonergic Systems That Regulate Fear And Panic

Central serotonin systems are major target for treating anxiety disorders with the use of selective serotonin (5-HT) reuptake inhibitors (SSRIs). Yet SSRIs tend to increase anxiety initially having their anxiolytic properties 2-3 weeks after daily treatment. There is pharmacological/electrophysiological evidence that 5-HT is largely excitatory in pro-fear regions such as the basolateral amygdala (BLA), but inhibitory on pro-panic orexin neurons in the perifornical hypothalamus (PeF). Using retrograde tracing we determined that the BLA and PeF are innervated by distinct serotonergic networks in the dorsal (DR) and median (MR) raphe with BLA projections outnumbering PeF projections 2:1. Here we sought to elucidate the role of these serotonergic networks on learned fear and innate panic responses.