SAT605 Growth Hormone Action In Somatostatin Neurons Regulates Anxiety And Fear Memory

Abstract

Abstract Disclosure: W.O. dos Santos: None. V.A. Juliano: None. H.R. Vieira: None. R. Frazao: None. C.D. Munhoz: None. J. Donato: None. Dysfunctions in growth hormone (GH) secretion increase the prevalence of anxiety and depression. Furthermore, GH receptor (GHR) signaling in the amygdala has been associated with fear memory, a key feature of post-traumatic stress disorder. However, it is currently unknown which neuronal population is targeted by GH action to influence neuropsychiatric diseases. Here we showed that approximately 60% of somatostatin (SST)-expressing neurons in the extended amygdala are directly responsive to GH. GHR ablation in SST-expressing cells (SSTΔGHR mice) led to increased anxiety in the light-dark box and elevated plus maze tests, whereas SSTΔGHR females showed no changes in anxiety, compared to control animals. Using auditory Pavlovian fear conditioning, both male and female SSTΔGHR mice exhibited a significant reduction in fear memory. In contrast, GHR ablation in SST neurons did not affect memory in the novel object recognition test. The gene expression was analyzed in a bilateral micropunch comprising the central nucleus of the amygdala and basolateral complex of male mice. Increased mRNA expression of Gabbr2 (GABAB2 receptor), Syp (synaptophysin), and Bdnf were observed in the amygdala of SSTΔGHR mice. In conclusion, GHR expression in SST neurons is necessary to regulate anxiety in males, but not in female mice. GHR ablation in SST neurons also decreases fear memory and affects the gene expression in the amygdala. Our findings identified for the first time a specific neuronal population responsible for mediating the effects of GH on behavioral aspects associated with neuropsychiatric diseases. Presentation: Saturday, June 17, 2023