Altered hippocampal-prefrontal communication during anxiety-related avoidance in mice deficient for the autism-associated gene Pogz.
Altered hippocampal-prefrontal communication during anxiety-related avoidance in mice deficient for the autism-associated gene Pogz.
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DOI：
10.7554/elife.54835
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发表时间：
2020-11-06
期刊：
影响因子：
7.7
通讯作者：
Sohal VS
中科院分区：
文献类型：
--
作者：
Cunniff MM;Markenscoff-Papadimitriou E;Ostrowski J;Rubenstein JL;Sohal VS
许多基因与自闭症有关。然而，目前尚不清楚这些基因的破坏会导致神经回路的长期变化，以及这些回路的变化如何导致异常行为。为了解决这些问题，我们研究了 Pogz（一种高置信度自闭症基因）杂合小鼠的行为和生理学。 Pogz+/- 小鼠在高架十字迷宫 (EPM) 中表现出与焦虑相关的回避减少。众所周知，腹侧海马 (vHPC) 和内侧前额叶皮层 (mPFC) 之间的 Theta 频率通信对于 EPM 中的正常回避是必要的。我们发现体内 vHPC 和 mPFC 之间的 θ 频率同步存在缺陷。当我们以更高分辨率检查 vHPC-mPFC 通信时，前额叶 GABA 能中间神经元的 vHPC 输入被特别破坏，而锥体神经元的输入保持完整。这些发现说明了高置信度自闭症基因的丢失如何通过在对特定行为重要的通路中引起抑制回路功能障碍来损害远距离交流。
Many genes have been linked to autism. However, it remains unclear what long-term changes in neural circuitry result from disruptions in these genes, and how these circuit changes might contribute to abnormal behaviors. To address these questions, we studied behavior and physiology in mice heterozygous for Pogz, a high confidence autism gene. Pogz+/- mice exhibit reduced anxiety-related avoidance in the elevated plus maze (EPM). Theta-frequency communication between the ventral hippocampus (vHPC) and medial prefrontal cortex (mPFC) is known to be necessary for normal avoidance in the EPM. We found deficient theta-frequency synchronization between the vHPC and mPFC in vivo. When we examined vHPC–mPFC communication at higher resolution, vHPC input onto prefrontal GABAergic interneurons was specifically disrupted, whereas input onto pyramidal neurons remained intact. These findings illustrate how the loss of a high confidence autism gene can impair long-range communication by causing inhibitory circuit dysfunction within pathways important for specific behaviors.