@article {69110, title = {Imaging neuronal voltage beyond the scattering limit}, journal = {Nat Methods}, year = {2025}, month = {2025 May 19}, abstract = {

Voltage imaging is a promising technique for high-speed recording of neuronal population activity. However, tissue scattering severely limits its application in dense neuronal populations. Here, we adopted the principle of localization microscopy, a technique that enables super-resolution imaging of single-molecules, to resolve dense neuronal activities\ in vivo. Leveraging the sparse activation of neurons during action potentials (APs), we precisely localize the fluorescence change associated with each AP, creating a super-resolution image of neuronal activities. This approach, termed\ Activity\ Localization\ Imaging (ALI), identifies overlapping neurons and separates their activities with over 10-fold greater precision than what tissue scattering permits. Using ALI, we simultaneously recorded over a hundred densely-labeled CA1 neurons, creating a map of hippocampal theta oscillation at single-cell and single-cycle resolution.

Preprint:\ https://doi.org/10.1101/2023.12.03.56840

}, doi = {10.1038/s41592-025-02692-5}, url = {https://doi.org/10.1038/s41592-025-02692-5}, author = {Tsai-Wen Chen and Xian-Bin Huang and Sarah E. Plutkis and Katie L. Holland and Luke D. Lavis and Bei-Jung Lin} } @article {69256, title = {Dendritic voltage imaging maps the biophysical basis of plateau potentials in the hippocampus}, journal = {bioRxiv}, year = {2024}, month = {2024 Mar 7}, abstract = {

Dendrites on neurons integrate synaptic inputs to determine spike timing. Dendrites also convey back-propagating action potentials (bAPs) which interact with synaptic inputs to produce plateau potentials and to mediate synaptic plasticity. The biophysical rules which govern the timing, spatial structures, and ionic character of dendritic excitations are not well understood. We developed molecular, optical, and computational tools to map sub-millisecond voltage dynamics throughout the dendritic trees of CA1 pyramidal neurons under diverse optogenetic and synaptic stimulus patterns, in acute brain slices. We observed history-dependent bAP propagation in distal dendrites, driven by locally generated Na+ spikes (dSpikes). Dendritic depolarization creates a transient window for dSpike propagation, opened by A-type KV channel inactivation, and closed by slow NaV inactivation. Collisions of dSpikes with synaptic inputs triggered calcium channel and N-methyl-D-aspartate receptor (NMDAR)-dependent plateau potentials, with accompanying complex spikes at the soma. This hierarchical ion channel network acts as a spike-rate accelerometer, providing an intuitive picture of how dendritic excitations shape associative plasticity rules.Competing Interest StatementThe authors have declared no competing interest.

}, doi = {10.1101/2023.06.02.543490}, url = {https://www.biorxiv.org/content/early/2024/03/07/2023.06.02.543490}, author = {Pojeong Park and J. David Wong-Campos and Daniel Itkis and Byung Hun Lee and Yitong Qi and Hunter C. Davis and Jonathan B. Grimm and Sarah E. Plutkis and Luke Lavis and Adam Ezra Cohen} } @article {69227, title = {A series of spontaneously blinking dyes for super-resolution microscopy}, journal = {bioRxiv}, year = {2024}, month = {2024 Feb 24}, abstract = {

Spontaneously blinking fluorophores permit the detection and localization of individual molecules without reducing buffers or caging groups, thus simplifying single-molecule localization microscopy (SMLM). The intrinsic blinking properties of such dyes are dictated by molecular structure and modulated by environment, which can limit utility. We report a series of tuned spontaneously blinking dyes with duty cycles that span two orders of magnitude, allowing facile SMLM in cells and dense biomolecular structures.

}, doi = {10.1101/2024.02.23.581625}, url = {https://www.biorxiv.org/content/early/2024/02/24/2024.02.23.581625}, author = {Katie L. Holland and Sarah E. Plutkis and Timothy A. Daugird and Abhishek Sau and Jonathan B. Grimm and Brian P. English and Qinsi Zheng and Sandeep Dave and Fariha Rahman and Liangqi Xie and Peng Dong and Ariana N. Tkachuk and Timothy A. Brown and Robert H. Singer and Zhe Liu and Catherine G. Galbraith and Siegfried M. Musser and Wesley R. Legant and Luke D. Lavis} } @article {68792, title = {Voltage dynamics of dendritic integration and back-propagation in vivo}, journal = {bioRxiv}, year = {2023}, month = {2023 May 26}, abstract = {

Neurons integrate synaptic inputs within their dendrites and produce spiking outputs, which then propagate down the axon and back into the dendrites where they contribute to plasticity. Mapping the voltage dynamics in dendritic arbors of live animals is crucial for understanding neuronal computation and plasticity rules. Here we combine patterned channelrhodopsin activation with dual-plane structured illumination voltage imaging, for simultaneous perturbation and monitoring of dendritic and somatic voltage in Layer 2/3 pyramidal neurons in anesthetized and awake mice. We examined the integration of synaptic inputs and compared the dynamics of optogenetically evoked, spontaneous, and sensory-evoked back-propagating action potentials (bAPs). Our measurements revealed a broadly shared membrane voltage throughout the dendritic arbor, and few signatures of electrical compartmentalization among synaptic inputs. However, we observed spike rate acceleration-dependent propagation of bAPs into distal dendrites. We propose that this dendritic filtering of bAPs may play a critical role in activity-dependent plasticity.

}, doi = {10.1101/2023.05.25.542363}, url = {https://doi.org/10.1101/2023.05.25.542363}, author = {J. David Wong-Campos and Pojeong Park and Hunter Davis and Yitong Qi and He Tian and Daniel G. Itkis and Doyeon Kim and Sarah E. Plutkis and Luke Lavis and Adam E. Cohen} }