Laboratory for Neuronal Circuit Dynamics, Imperial College London, London W12 0NN, UK.
Institute of Psychopharmacology, Central Institute of Mental Health, Medical Faculty Mannheim, University of Heidelberg, 69115 Heidelberg, Germany.
Int J Mol Sci. 2023 May 30;24(11):9463. doi: 10.3390/ijms24119463.
(1) From mouse to man, shaking behavior (head twitches and/or wet dog shakes) is a reliable readout of psychedelic drug action. Shaking behavior like psychedelia is thought to be mediated by serotonin 2A receptors on cortical pyramidal cells. The involvement of pyramidal cells in psychedelic-induced shaking behavior remains hypothetical, though, as experimental in vivo evidence is limited. (2) Here, we use cell type-specific voltage imaging in awake mice to address this issue. We intersectionally express the genetically encoded voltage indicator VSFP Butterfly 1.2 in layer 2/3 pyramidal neurons. We simultaneously capture cortical hemodynamics and cell type-specific voltage activity while mice display psychedelic shaking behavior. (3) Shaking behavior is preceded by high-frequency oscillations and overlaps with low-frequency oscillations in the motor cortex. Oscillations spectrally mirror the rhythmics of shaking behavior and reflect layer 2/3 pyramidal cell activity complemented by hemodynamics. (4) Our results reveal a clear cortical fingerprint of serotonin-2A-receptor-mediated shaking behavior and open a promising methodological avenue relating a cross-mammalian psychedelic effect to cell-type specific brain dynamics.
（1）从老鼠到人，震颤行为（头部抽搐和/或湿狗抖动）是致幻药物作用的可靠指标。像迷幻药一样的震颤行为被认为是由皮质锥体神经元上的 5-羟色胺 2A 受体介导的。然而，锥体细胞在致幻剂引起的震颤行为中的参与仍然是假设的，因为实验体内证据有限。（2）在这里，我们使用清醒小鼠中的细胞类型特异性电压成像来解决这个问题。我们在层 2/3 锥体神经元中交叉表达基因编码的电压指示剂 VSFPbutterfly 1.2。当老鼠表现出致幻性震颤行为时，我们同时捕获皮质血液动力学和细胞类型特异性电压活动。（3）震颤行为之前是高频振荡，与运动皮层中的低频振荡重叠。振荡在频谱上反映了震颤行为的节奏，并反映了补充血液动力学的层 2/3 锥体细胞活动。（4）我们的结果揭示了 5-羟色胺 2A 受体介导的震颤行为的明显皮质指纹，并为将跨哺乳动物致幻效应与特定于细胞类型的大脑动力学联系起来开辟了一条有前途的方法学途径。
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