Donahue Margaret M, Robson Emma, Colgin Laura Lee
Center for Learning and Memory, The University of Texas at Austin, Austin, TX 78712.
Institute for Neuroscience, The University of Texas at Austin, Austin, TX 78712.
bioRxiv. 2025 Feb 13:2024.10.18.619112. doi: 10.1101/2024.10.18.619112.
Fragile X Syndrome (FXS) is a neurodevelopmental disorder that can cause impairments in spatial cognition and memory. The hippocampus is thought to support spatial cognition through the activity of place cells, neurons with spatial receptive fields. Coordinated firing of place cell populations is organized by different oscillatory patterns in the hippocampus during specific behavioral states. Theta rhythms organize place cell populations during awake exploration. Sharp wave-ripples organize place cell population reactivation during waking rest. Here, we examined the coordination of CA1 place cell populations during active behavior and subsequent rest in a rat model of FXS ( knockout rats). While the organization of individual place cells by the theta rhythm was normal, the coordinated activation of sequences of place cells during individual theta cycles was impaired in knockout rats. Further, the subsequent replay of place cell sequences was impaired during waking rest following active exploration. Together, these results expand our understanding of how genetic modifications that model those observed in FXS affect hippocampal physiology and suggest a potential mechanism underlying impaired spatial cognition in FXS.
脆性X综合征（FXS）是一种神经发育障碍，可导致空间认知和记忆受损。海马体被认为通过位置细胞（具有空间感受野的神经元）的活动来支持空间认知。在特定行为状态下，海马体中不同的振荡模式会组织位置细胞群体的协同放电。θ节律在清醒探索期间组织位置细胞群体。尖锐波涟漪在清醒休息期间组织位置细胞群体的重新激活。在此，我们研究了FXS大鼠模型（基因敲除大鼠）在主动行为和随后休息期间CA1位置细胞群体的协调性。虽然θ节律对单个位置细胞的组织是正常的，但在基因敲除大鼠中，单个θ周期内位置细胞序列的协同激活受损。此外，在主动探索后的清醒休息期间，位置细胞序列的后续重放也受损。这些结果共同扩展了我们对模拟FXS中观察到的基因修饰如何影响海马体生理学的理解，并提示了FXS中空间认知受损的潜在机制。
