Recently, a collaboration between the research teams led by Bi Guoqiang at the Institute of Brain Disorders and Brain Cognitive Research, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences / Shenzhen-Hong Kong Institute of Brain Science, University of Science and Technology of China, and Zhou Pengcheng at Shenzhen Polytechnic University (provisional) has resulted in the development of TINIscope, the world's lightest head-mounted fluorescence microscope, weighing merely 0.43 grams. This innovative device has successfully achieved synchronous imaging of calcium activities in four subregions of the hippocampus in freely moving mice.
Experimental mice wearing four TINIscope microscopes - real-life images.
These microscopes offer neuroscientists a crucial new tool to explore the cross-brain region coordination at the neuronal level in animals' perception, cognition, and behavior. The related research was recently published in the "National Science Review."
Traditional head-mounted devices weigh around 2 grams, and implanting four devices on the heads of small animals such as mice would impede their normal free movement due to the substantial additional weight. In this study, researchers utilized image sensor (CMOS) chips with serial output functionality and smaller dimensions, eliminating the use of serializer chips, thereby minimizing the additional circuitry functions in the head-mounted part and addressing signal transmission issues.
In terms of optics, the fluorescence excitation optical path (LED side) and the acquisition optical path (CMOS side) of the head-mounted device are typically arranged vertically, with the larger CMOS side in the vertical direction in traditional devices. However, the limited head space of mice makes it impossible to place four devices simultaneously. Researchers modified the TINIscope's optical design to make it easier to arrange on the head. The TINIscope allows for easy adjustment of angles during installation and enables synchronous imaging of two brain areas with a minimum spacing of 1.2 millimeters, essentially achieving synchronous recording of any four target brain areas. Researchers also developed a reorientation device and a complete experimental acquisition system to address the issue of cable entanglement during animals' free movement.
Additionally, researchers marked neurons in the four subregions of the mouse hippocampus with calcium concentration indicator proteins and used TINIscope for synchronous imaging of the four brain areas, validating the reliability of the data collected by the devices. Through quantitative behavioral analysis, wearing four devices did not significantly affect the mice's free movement. Researchers recorded neuronal activity in the four hippocampal subregions of mice in both the T-maze and open-field environments, finding that approximately 25% of neuronal subpopulations exhibited spatial modulation characteristics.
Screenshot of the paper.
