焦虑症是最普遍的心理健康障碍之一。几行证据暗示了皮质区域,如内侧前额叶皮质,眶额叶皮质,和岛状皮层以及海马在动物模型中自上而下调节焦虑样行为。两种啮齿动物模型的焦虑,以及抗焦虑药物治疗,导致多个前脑区域的伴随激活。这里,我们试图研究前脑主神经元的化学激活或抑制对焦虑和绝望样行为的影响。我们分别使用hM3Dq或hM4Di设计者受体(DREADD)专门激活或抑制了Ca2/钙调蛋白依赖性蛋白激酶IIα(CamKIIα)阳性前脑兴奋性神经元。通过立即早期基因表达的增加证实了电路激活,c-Fos,在海马和大脑皮层.然后,我们检查了DREADD介导的前脑兴奋性神经元激活对焦虑和绝望样行为行为测试的影响。我们的结果表明,前脑兴奋性神经元的急性hM3DqDREADD激活导致开放视野中焦虑样行为的显着下降,明暗避免,和高架迷宫测试。相比之下,hM3DqDREADD激活前脑兴奋性神经元不会改变尾巴悬吊或强迫游泳测试中的绝望样行为。急性hM4DiDREADD抑制CamKIIα阳性前脑兴奋性神经元不会改变焦虑或绝望样行为。一起来看,我们的结果证明,前脑兴奋性神经元的化学遗传激活降低了小鼠的焦虑样行为。
Anxiety disorders are amongst the most prevalent mental health disorders. Several lines of evidence have implicated cortical regions such as the medial prefrontal cortex, orbitofrontal cortex, and insular cortex along with the hippocampus in the top-down modulation of anxiety-like behaviour in animal models. Both rodent models of anxiety, as well as treatment with anxiolytic drugs, result in the concomitant activation of multiple forebrain regions. Here, we sought to examine the effects of chemogenetic activation or inhibition of forebrain principal neurons on anxiety and despair-like behaviour. We acutely activated or inhibited Ca2+/calmodulin-dependent protein kinase II α (CamKIIα)-positive forebrain excitatory neurons using the
hM3Dq or the hM4Di Designer Receptor Exclusively Activated by Designer Drug (DREADD) respectively. Circuit activation was confirmed via an increase in expression of the immediate early gene, c-Fos, within both the hippocampus and the neocortex. We then examined the influence of DREADD-mediated activation of forebrain excitatory neurons on behavioural tests for anxiety and despair-like behaviour. Our results indicate that acute
hM3Dq DREADD activation of forebrain excitatory neurons resulted in a significant decline in anxiety-like behaviour on the open field, light-dark avoidance, and the elevated plus maze test. In contrast,
hM3Dq DREADD activation of forebrain excitatory neurons did not alter despair-like behaviour on either the tail suspension or forced swim tests. Acute hM4Di DREADD inhibition of CamKIIα-positive forebrain excitatory neurons did not modify either anxiety or despair-like behaviour. Taken together, our results demonstrate that chemogenetic activation of excitatory neurons in the forebrain decreases anxiety-like behaviour in mice.