Elsaafien Khalid, Kirchner Matthew K, Scott Karen A, Spector Eliot A, Mowry Francesca E, Sumners Colin, Stern Javier E, de Kloet Annette D, Krause Eric G
Neuroscience Institute, College of Arts and Sciences, Georgia State University, Atlanta, Georgia 30303.
Center for Neuroinflammation and Cardiometabolic Diseases, College of Arts and Sciences Georgia State University, Atlanta, Georgia 30303.
J Neurosci. 2025 Mar 19;45(12):e1482242025. doi: 10.1523/JNEUROSCI.1482-24.2025.
Relief from psychological stress confers cardio-protection by altering brain activity and lowering blood pressure; however, the neuronal circuits orchestrating these effects are unknown. Here, we used male mice to discern neuronal circuits conferring stress relief and reduced blood pressure. We found that neurons residing in the central nucleus of the amygdala (CeA) expressing angiotensin type 2 receptors (ATR), deemed CeA, innervate brain nuclei regulating stress responding. In vivo optogenetic excitation of CeA lowered blood pressure, and this effect was abrogated by systemic hexamethonium or antagonism of GABA receptors within the CeA. Intriguingly, in vivo optogenetic excitation of CeA was also potently anxiolytic. Delivery of an ATR agonist into the CeA recapitulated the hypotensive and anxiolytic effects, but ablating ATR(s) from the CeA was anxiogenic. The results suggest that the excitation of CeA couples lowered blood pressure with anxiolysis. The implication is that therapeutics targeting CeA may provide stress relief and protection against cardiovascular disease.
心理压力的缓解通过改变大脑活动和降低血压来赋予心脏保护作用;然而,协调这些效应的神经回路尚不清楚。在这里,我们使用雄性小鼠来识别赋予压力缓解和血压降低作用的神经回路。我们发现,杏仁核中央核(CeA)中表达2型血管紧张素受体(ATR)的神经元,即CeA神经元,支配调节应激反应的脑核。CeA的体内光遗传学兴奋可降低血压,而全身注射六甲铵或CeA内GABA受体的拮抗作用可消除这种效应。有趣的是,CeA的体内光遗传学兴奋也具有显著的抗焦虑作用。将ATR激动剂注入CeA可重现降压和抗焦虑作用,但从CeA中去除ATR会产生致焦虑作用。结果表明,CeA的兴奋将血压降低与抗焦虑作用联系起来。这意味着靶向CeA的疗法可能提供压力缓解并预防心血管疾病。