How individual neurons perform sensorimotor integration in vivo is poorly understood because it is difficult to measure activity within morphologically complex 3D structures, such as dendrites. Another challenge arises from brain-motion artifacts that are inevitably present in experiments on awake-behaving animals, which cause small structures like dendrites to move in and out of the region of interest. To overcome these issues, our laboratory has developed two cutting-edge techniques: 2-photon acousto-optic lens (AOL) 3D microscopy, which achieves ultra-fast recordings and selective imaging of regions of interest distributed within the imaging volume, and real-time, on-line motion compensation, which nearly eliminates brain-motion artifacts during the experiment. Combining these tools with our novel semi-automated 3D dendritic tracing has enabled stable and reliable recordings simultaneously from somata, dendrites, and synaptic spines. We thus carried out, for the first time, selective imaging of neuronal activity from a large fraction of the entire dendritic tree of excitatory pyramidal cells in motor and visual cortices in awake behaving mice. Our results are revealing the spatial and temporal extent of dendritic activity within and across various types of neurons, brain regions, and levels of network activity, providing fundamental insights into how sensorimotor information is integrated by single cells and routed through neural circuits in vivo.
Findings from this research have been and will continue to be shared with scientists and the public. The broader impacts include: advancing neuroscience research and technology, developing collaborations and innovation, and sparking public interest in the brain. The potential socio-economic impacts include: advancing scientific knowledge via presenting data at international specialized scientific conferences and publications in respected international peer-reviewed open-access journals to give broad visibility to scientists and the public; facilitating international collaborations aimed at exploiting 3D imaging technologies; and making pertinent data-sets, metadata, and computer codes available for further exploitation via mining, verification, and reuse. The potential societal impacts include: improving our mechanistic understanding of normal brain function; development of new methods to test and treat brain disorder and disease; new ways of visualizing neuronal computations in 3D for use as educational tools; and inspiring the next generation of scientists through laboratory demonstrations and non-specialist presentations.
