@article {49535, title = {Brain-wide circuit interrogation at the cellular level guided by online analysis of neuronal function.}, journal = {Nature Methods}, volume = {15}, year = {2018}, month = {2018 Nov 30}, pages = {1117-1125}, abstract = {

Whole-brain imaging allows for comprehensive functional mapping of distributed neural pathways, but neuronal perturbation experiments are usually limited to targeting predefined regions or genetically identifiable cell types. To complement whole-brain measures of activity with brain-wide manipulations for testing causal interactions, we introduce a system that uses measuredactivity patterns to guide optical perturbations of any subset of neurons in the same fictively behaving larval zebrafish. First, a light-sheet microscope collects whole-brain data that are rapidly analyzed by a distributed computing system to generate functional brain maps. On the basis of these maps, the experimenter can then optically ablate neurons and image activity changes across the brain. We applied this method to characterize contributions of behaviorally tuned populations to the optomotor response. We extended the system to optogenetically stimulate arbitrary subsets of neurons during whole-brain imaging. These open-source methods enable delineating the contributions of neurons to brain-wide circuit dynamics and behavior in individual animals.

}, doi = {10.1038/s41592-018-0221-x}, author = {Vladimirov, Nikita and Wang, Chen and H{\"o}ckendorf, Burkhard and Pujala, Avinash and Tanimoto, Masashi and Mu, Yu and Yang, Chao-Tsung and Wittenbach, Jason and Freeman, Jeremy and Preibisch, Stephan and Koyama, Minoru and Keller, Philipp J and Ahrens, Misha B} } @article {47239, title = {Minimally invasive microendoscopy system for in vivo functional imaging of deep nuclei in the mouse brain.}, journal = {Biomedical Optics Express}, volume = {6}, year = {2015}, month = {2015 Nov 1}, pages = {4546-56}, abstract = {

The ability to image neurons anywhere in the mammalian brain is a major goal of optical microscopy. Here we describe a minimally invasive microendoscopy system for studying the morphology and function of neurons at depth. Utilizing a guide cannula with an ultrathin wall, we demonstrated in vivo two-photon fluorescence imaging of deeply buried nuclei such as the striatum (2.5 mm depth), substantia nigra (4.4 mm depth) and lateral hypothalamus (5.0 mm depth) in mouse brain. We reported, for the first time, the observation of neuronal activity with subcellular resolution in the lateral hypothalamus and substantia nigra of head-fixed awake mice.

}, issn = {2156-7085}, doi = {10.1364/BOE.6.004546}, author = {Bocarsly, Miriam E and Jiang, Wan-Chen and Wang, Chen and Dudman, Joshua T and Ji, Na and Aponte, Yeka} } @article {45373, title = {Multiplexed aberration measurement for deep tissue imaging in vivo.}, journal = {Nature Methods}, year = {2014}, month = {2014 Aug 17}, abstract = {

We describe an adaptive optics method that modulates the intensity or phase of light rays at multiple pupil segments in parallel to determine the sample-induced aberration. Applicable to fluorescent protein-labeled structures of arbitrary complexity, it allowed us to obtain diffraction-limited resolution in various samples in vivo. For the strongly scattering mouse brain, a single aberration correction improved structural and functional imaging of fine neuronal processes over a large imaging volume.

}, issn = {1548-7105}, doi = {10.1038/nmeth.3068}, author = {Wang, Chen and Liu, Rui and Milkie, Daniel E and Sun, Wenzhi and Tan, Zhongchao and Kerlin, Aaron and Chen, Tsai-Wen and Kim, Douglas S and Ji, Na} } @article {6675, title = {Characterization and improvement of three-dimensional imaging performance of GRIN-lens-based two-photon fluorescence endomicroscopes with adaptive optics.}, journal = {Optics Express}, volume = {21}, year = {2013}, month = {2013 Nov 4}, pages = {27142-54}, abstract = {

Inherent aberrations of gradient index (GRIN) lenses used in fluorescence endomicroscopes deteriorate imaging performance. Using adaptive optics, we characterized and corrected the on-axis and off-axis aberrations of a GRIN lens with NA 0.8 at multiple focal planes. We demonstrated a rotational-transformation-based correction procedure, which enlarged the imaging area with diffraction-limited resolution with only two aberration measurements. 204.8 {\texttimes} 204.8 {\textmu}m2 images of fluorescent beads and brain slices before and after AO corrections were obtained, with evident improvements in both image sharpness and brightness after AO correction. These results show great promises of applying adaptive optical two-photon fluorescence endomicroscope to three-dimensional (3D) imaging.

}, issn = {1094-4087}, doi = {10.1364/OE.21.027142}, author = {Wang, Chen and Ji, Na} } @article {1449, title = {Cortical representations of olfactory input by trans-synaptic tracing.}, journal = {Nature}, volume = {472}, year = {2010}, month = {2010 Dec 22}, pages = {191-6}, abstract = {

In the mouse, each class of olfactory receptor neurons expressing a given odorant receptor has convergent axonal projections to two specific glomeruli in the olfactory bulb, thereby creating an odour map. However, it is unclear how this map is represented in the olfactory cortex. Here we combine rabies-virus-dependent retrograde mono-trans-synaptic labelling with genetics to control the location, number and type of {\textquoteright}starter{\textquoteright} cortical neurons, from which we trace their presynaptic neurons. We find that individual cortical neurons receive input from multiple mitral cells representing broadly distributed glomeruli. Different cortical areas represent the olfactory bulb input differently. For example, the cortical amygdala preferentially receives dorsal olfactory bulb input, whereas the piriform cortex samples the whole olfactory bulb without obvious bias. These differences probably reflect different functions of these cortical areas in mediating innate odour preference or associative memory. The trans-synaptic labelling method described here should be widely applicable to mapping connections throughout the mouse nervous system.

}, issn = {1476-4687}, doi = {10.1038/nature09714}, author = {Miyamichi, Kazunari and Amat, Fernando and Moussavi, Farshid and Wang, Chen and Wickersham, Ian and Wall, Nicholas R and Taniguchi, Hiroki and Tasic, Bosiljka and Huang, Z Josh and He, Zhigang and Callaway, Edward M and Horowitz, Mark A and Luo, Liqun} }