<br>光遗传学揭示海马 CA1 和 CA3 中矛盾的网络稳定性,Current Biology

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光遗传学揭示海马 CA1 和 CA3 中矛盾的网络稳定性
Current Biology ( IF 8.1 ) Pub Date : 2023-04-05 , DOI: 10.1016/j.cub.2023.03.032
Laurel Watkins de Jong ₁ , Mohammadreza Mohagheghi Nejad ₂ , Euisik Yoon ₃ , Sen Cheng ₂ , Kamran Diba ₄

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兴奋性神经元之间的循环连接和抑制性神经元的反馈强度是神经元回路的动力学和计算特性的关键决定因素。为了更好地了解海马 CA1 和 CA3 区域的这些电路特性，我们对麻醉下和安静清醒的大鼠进行光遗传学操作，结合大规模单位记录，使用不同光敏视蛋白的光抑制和光激发。在这两个区域中，我们都看到了惊人的矛盾反应：部分细胞在光抑制期间增加了放电，而其他细胞在光激发期间减少了放电。这些矛盾的反应在 CA3 中比在 CA1 中更为突出，但值得注意的是，CA1 中间神经元显示出响应 CA3 光抑制的放电增加。这些观察结果在模拟中得到了重述，我们将 CA1 和 CA3 建模为抑制稳定网络，其中强烈的循环激励通过反馈抑制来平衡。为了直接测试抑制稳定模型，我们针对 (GAD-Cre) 抑制细胞进行了大规模光抑制，发现两个区域的中间神经元在光抑制时都会增加放电，正如预测的那样。我们的结果强调了光遗传学操作过程中经常出现的自相矛盾的回路动力学，并表明与长期存在的教条相反，CA1 和 CA3 海马区域都表现出强烈的反复兴奋，并通过抑制来稳定。

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Optogenetics reveals paradoxical network stabilizations in hippocampal CA1 and CA3

Recurrent connectivity between excitatory neurons and the strength of feedback from inhibitory neurons are critical determinants of the dynamics and computational properties of neuronal circuits. Toward a better understanding of these circuit properties in regions CA1 and CA3 of the hippocampus, we performed optogenetic manipulations combined with large-scale unit recordings in rats under anesthesia and in quiet waking, using photoinhibition and photoexcitation with different light-sensitive opsins. In both regions, we saw striking paradoxical responses: subsets of cells increased firing during photoinhibition, while other cells decreased firing during photoexcitation. These paradoxical responses were more prominent in CA3 than in CA1, but, notably, CA1 interneurons showed increased firing in response to photoinhibition of CA3. These observations were recapitulated in simulations where we modeled both CA1 and CA3 as inhibition-stabilized networks in which strong recurrent excitation is balanced by feedback inhibition. To directly test the inhibition-stabilized model, we performed large-scale photoinhibition directed at (GAD-Cre) inhibitory cells and found that interneurons in both regions increased firing when photoinhibited, as predicted. Our results highlight the often-paradoxical circuit dynamics that are evidenced during optogenetic manipulations and indicate that, contrary to long-standing dogma, both CA1 and CA3 hippocampal regions display strongly recurrent excitation, which is stabilized through inhibition.

更新日期：2023-04-05

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