Laboratory of Systems Neuroscience, Department of Physiology, University of Bern, Bühlplatz 5, 3012 Bern, Switzerland.
Laboratory of Systems Neuroscience, Department of Physiology, University of Bern, Bühlplatz 5, 3012 Bern, Switzerland.
Prog Neurobiol. 2022 Dec;219:102368. doi: 10.1016/j.pneurobio.2022.102368. Epub 2022 Oct 20.
Anxiety is an aversive mood reflecting the anticipation of potential threats. The ventral hippocampus (vH) is a key brain region involved in the genesis of anxiety responses. Recent studies have shown that anxiety is mediated by the activation of vH pyramidal neurons targeting various limbic structures. Throughout the cortex, the activity of pyramidal neurons is controlled by GABA-releasing inhibitory interneurons and the GABAergic system represents an important target of anxiolytic drugs. However, how the activity of vH inhibitory interneurons is related to different anxiety behaviours has not been investigated so far. Here, we integrated in vivo electrophysiology with behavioural phenotyping of distinct anxiety exploration behaviours in rats. We showed that pyramidal neurons and interneurons of the vH are selectively active when animals explore specific compartments of the elevated-plus-maze (EPM), an anxiety task for rodents. Moreover, rats with prior goal-related experience exhibited low-anxiety exploratory behaviour and showed a larger trajectory-related activity of vH interneurons during EPM exploration compared to high anxiety rats. Finally, in low anxiety rats, trajectory-related vH interneurons exhibited opposite activity to pyramidal neurons specifically in the open arms (i.e. more anxiogenic) of the EPM. Our results suggest that vH inhibitory micro-circuits could act as critical elements underlying different anxiety states.
焦虑是一种厌恶情绪,反映了对潜在威胁的预期。腹侧海马体(vH)是参与焦虑反应发生的关键脑区。最近的研究表明,焦虑是通过靶向各种边缘结构的 vH 锥体神经元的激活来介导的。在整个皮层中,锥体神经元的活动受 GABA 释放抑制性中间神经元的控制,而 GABA 能系统是抗焦虑药物的重要靶点。然而,迄今为止,vH 抑制性中间神经元的活动与不同的焦虑行为有何关系尚不清楚。在这里,我们将体内电生理学与大鼠不同焦虑探索行为的行为表型相结合进行研究。我们表明,当动物探索高架十字迷宫(EPM)的特定隔间时,vH 的锥体神经元和中间神经元是选择性活跃的,EPM 是一种用于啮齿动物的焦虑任务。此外,具有先前目标相关经验的大鼠表现出低焦虑探索行为,并在 EPM 探索期间显示出更大的与轨迹相关的 vH 中间神经元活动,而高焦虑大鼠则表现出更小的与轨迹相关的 vH 中间神经元活动。最后,在低焦虑大鼠中,与轨迹相关的 vH 中间神经元在 EPM 的开放臂(即更焦虑)中表现出与锥体神经元相反的活动。我们的研究结果表明,vH 抑制性微电路可能是不同焦虑状态的关键因素。
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