Liu Yuehan, Zhang Jing, Guo Dian, Li Yipeng, Zhang Haolin, Park Hyeon-Cheol, Jing Wenhe, Lu Hui, Li Xingde
Johns Hopkins University, Department of Electrical and Computer Engineering, Baltimore, Maryland, United States.
Johns Hopkins University, Department of Biomedical Engineering, Baltimore, Maryland, United States.
Neurophotonics. 2025 Apr;12(2):025016. doi: 10.1117/1.NPh.12.2.025016. Epub 2025 Jun 18.
The recently developed two-photon (2P) fiberscope offers attractive opportunities in neuroscience by enabling high-resolution neural imaging in freely behaving rodents. However, like other miniature 2P devices, it involves a tether (for fiber and scanner drive wires), which inevitably limits the animal's movement, especially its rotation.
We aim to develop a platform for 2P fiberscopes (and other tethered miniature devices), enabling rotational resistance-free neuroimaging in freely rotating/walking rodents.
We introduced a proactive optoelectrical commutator (pOEC) capable of real-time sensing and compensation for a tiny torque buildup in the tether (with a preselected threshold), preemptively eliminating the rotational resistance when the mouse physically rotates the fiberscope.
Experimental results demonstrated that the pOEC effectively compensates for torque buildup in the fiberscope, thereby maintaining stable 2P imaging performance. In addition, the system minimizes the rotational resistance imposed by the head-mounted tether, enabling near-zero rotational burden during 2P neural imaging in freely behaving mice. Investigations of neural activity further revealed that a considerable proportion of motor cortex neurons exhibited statistically significant changes in their firing patterns when the mouse was restricted by tether-induced rotational resistance or completely immobilized via head fixation.
The results indicated that rotational restriction induced visible impacts on neuronal activities. Our platform offers a promising opportunity for studying dynamic neural circuit functions under nearly natural conditions with minimized impacts by the rotational restriction.
最近开发的双光子（2P）纤维镜通过在自由活动的啮齿动物中实现高分辨率神经成像，为神经科学提供了诱人的机会。然而，与其他微型2P设备一样，它涉及一根系绳（用于光纤和扫描仪驱动线），这不可避免地限制了动物的活动，尤其是其旋转。
我们旨在开发一个用于2P纤维镜（和其他系留微型设备）的平台，在自由旋转/行走的啮齿动物中实现无旋转阻力的神经成像。
我们引入了一种主动光电换向器（pOEC），它能够实时感知并补偿系绳中微小扭矩的积累（达到预选阈值），在小鼠实际旋转纤维镜时预先消除旋转阻力。
实验结果表明，pOEC有效地补偿了纤维镜中的扭矩积累，从而保持了稳定的2P成像性能。此外，该系统将头戴式系绳施加的旋转阻力降至最低，在自由活动小鼠的2P神经成像过程中实现了近乎零的旋转负担。对神经活动的研究进一步表明，当小鼠受到系绳引起的旋转阻力限制或通过头部固定完全固定时，相当一部分运动皮层神经元的放电模式表现出统计学上的显著变化。
结果表明，旋转限制对神经元活动产生了明显影响。我们的平台为在近乎自然的条件下研究动态神经回路功能提供了一个有前景的机会，同时将旋转限制的影响降至最低。
