Department of Psychiatry, Weill Institute for Neurosciences, and Kavli Institute for Fundamental Neuroscience, University of California, San Francisco, San Francisco, United States.
Elife. 2020 Nov 6;9:e54835. doi: 10.7554/eLife.54835.
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 , a high confidence autism gene. 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.
许多基因都与自闭症有关。然而，目前尚不清楚这些基因的破坏会导致神经回路的哪些长期变化，以及这些回路变化如何导致异常行为。为了解决这些问题，我们研究了杂合子（一种高可信度自闭症基因）的小鼠的行为和生理学。杂合子小鼠在高架十字迷宫（EPM）中表现出焦虑相关回避减少。已知腹侧海马体（vHPC）和内侧前额叶皮层（mPFC）之间的θ频带通信对于正常回避是必要的。我们发现 vHPC 和 mPFC 之间的θ频带同步存在缺陷。当我们以更高的分辨率检查 vHPC-mPFC 通信时，发现 vHPC 对前额叶 GABA 能中间神经元的输入被特异性破坏，而对锥体神经元的输入则保持完整。这些发现说明了高可信度自闭症基因的缺失如何通过引起对特定行为重要的通路中的抑制性回路功能障碍来损害长程通信。
