Exploring the relationship between neuronal dynamics and ethologically relevant behaviour involves recording neuronal-population activity using technologies that are compatible with unrestricted animal behaviour. However, head-mounted microscopes that accommodate weight limits to allow for free animal behaviour typically compromise field of view, resolution or depth range, and are susceptible to movement-induced artefacts. Here we report a miniaturized head-mounted fluorescent mesoscope that we systematically optimized for calcium imaging at single-neuron resolution, for increased fields of view and depth of field, and for robustness against motion-generated artefacts. Weighing less than 2.5 g, the mesoscope enabled recordings of neuronal-population activity at up to 16 Hz, with 4 μm resolution over 300 μm depth-of-field across a field of view of 3.6 × 3.6 mm² in the cortex of freely moving mice. We used the mesoscope to record large-scale neuronal-population activity in socially interacting mice during free exploration and during fear-conditioning experiments, and to investigate neurovascular coupling across multiple cortical regions.

探索神经元动力学与行为学相关行为之间的关系涉及使用与不受限制的动物行为兼容的技术来记录神经元群体活动。然而，头戴式显微镜适应重量限制以允许动物自由活动，通常会损害视野、分辨率或深度范围，并且容易受到运动引起的伪影的影响。在这里，我们报告了一种小型头戴式荧光介观镜，我们系统地优化了单神经元分辨率的钙成像，以增加视野和景深，并提高对运动产生的伪影的鲁棒性。该介观镜重量不到 2.5 g，能够以高达 16 Hz 的频率记录神经元群活动，在自由运动的皮层中，在 3.6 × 3.6 mm ²的视野范围内，分辨率为 4 μm，景深超过 300 μm老鼠。我们使用介观镜记录了社交互动小鼠在自由探索和恐惧调节实验期间的大规模神经元群活动，并研究了跨多个皮质区域的神经血管耦合。