@article {69847, title = {Fast, accurate, and versatile data analysis platform for the quantification of molecular spatiotemporal signals.}, journal = {Cell}, year = {2025}, month = {2025 Apr 04}, abstract = {

Optical recording of intricate molecular dynamics is becoming an indispensable technique for biological studies, accelerated by the development of new or improved biosensors and microscopy technology. This creates major computational challenges to extract and quantify biologically meaningful spatiotemporal patterns embedded within complex and rich data sources, many of which cannot be captured with existing methods. Here, we introduce activity quantification and analysis (AQuA2), a fast, accurate, and versatile data analysis platform built upon advanced machine-learning techniques. It decomposes complex live-imaging-based datasets into elementary signaling events, allowing accurate and unbiased quantification of molecular activities and identification of consensus functional units. We demonstrate applications across a wide range of biosensors, cell types, organs, animal models, microscopy techniques, and imaging approaches. As exemplar findings, we show how AQuA2 identified drug-dependent interactions between neurons and astroglia, as well as distinct sensorimotor signal propagation patterns in the mouse spinal cord.

Preprint:\ https://doi.org/10.1101/2024.05.02.592259

}, issn = {1097-4172}, doi = {10.1016/j.cell.2025.03.012}, url = {https://doi.org/10.1016/j.cell.2025.03.012}, author = {Mi, Xuelong and Chen, Alex Bo-Yuan and Duarte, Daniela and Carey, Erin and Taylor, Charlotte R and Braaker, Philipp N and Bright, Mark and Almeida, Rafael G and Lim, Jing-Xuan and Ruetten, Virginia M S and Wang, Yizhi and Wang, Mengfan and Zhang, Weizhan and Zheng, Wei and Reitman, Michael E and Huang, Yongkang and Wang, Xiaoyu and Li, Lei and Deng, Hanfei and Shi, Song-Hai and Poskanzer, Kira E and Lyons, David A and Nimmerjahn, Axel and Ahrens, Misha B and Yu, Guoqiang} } @article {67821, title = {A genetically defined insula-brainstem circuit selectively controls motivational vigor.}, journal = {Cell}, year = {2021}, month = {2021 Dec 07}, abstract = {

The anterior insular cortex (aIC) plays a critical role in cognitive and motivational control of behavior, but the underlying neural mechanism remains elusive. Here, we show that aIC neurons expressing Fezf2 (aIC), which are the pyramidal tract neurons, signal motivational vigor and invigorate need-seeking behavior through projections to the brainstem nucleus tractus solitarii (NTS). aIC neurons and their postsynaptic NTS neurons acquire anticipatory activity through learning, which encodes the perceived value and the vigor of actions to pursue homeostatic needs. Correspondingly, aIC {\textrightarrow} NTS circuit activity controls vigor, effort, and striatal dopamine release but only if the action is learned and the outcome is needed. Notably, aIC neurons do not represent taste or valence. Moreover, aIC {\textrightarrow} NTS activity neither drives reinforcement nor influences total consumption. These results pinpoint specific functions of aIC {\textrightarrow} NTS circuit for selectively controlling motivational vigor and suggest that motivation is subserved, in part, by aIC{\textquoteright}s top-down regulation of dopamine signaling.

}, issn = {1097-4172}, doi = {10.1016/j.cell.2021.11.019}, author = {Deng, Hanfei and Xiao, Xiong and Yang, Tao and Ritola, Kimberly and Hantman, Adam and Li, Yulong and Huang, Z Josh and Li, Bo} } @article {65739, title = {A genetically defined compartmentalized striatal direct pathway for negative reinforcement.}, journal = {Cell}, volume = {181}, year = {2020}, month = {2020 Oct 1}, pages = {211}, abstract = {

The striosome compartment within the dorsal striatum has been implicated in reinforcement learning and regulation of motivation, but how striosomal neurons contribute to these functions remains elusive. Here, we show that a genetically identified striosomal population, which expresses the Teashirt family zinc finger 1 (Tshz1) and belongs to the direct pathway, drives negative reinforcement and is essential for aversive learning in mice. Contrasting a "conventional" striosomal direct pathway, the Tshz1 neurons cause aversion, movement suppression, and negative reinforcement once activated, and they receive a distinct set of synaptic inputs. These neurons are predominantly excited by punishment rather than reward and represent the anticipation of punishment or the motivation for avoidance. Furthermore, inhibiting these neurons impairs punishment-based learning without affecting reward learning or movement. These results establish a major role of striosomal neurons in behaviors reinforced by punishment and moreover uncover functions of the direct pathway unaccounted for in classic models.

}, issn = {1097-4172}, doi = {10.1016/j.cell.2020.08.032}, author = {Xiao, Xiong and Deng, Hanfei and Furlan, Alessandro and Yang, Tao and Zhang, Xian and Hwang, Ga-Ram and Tucciarone, Jason and Wu, Priscilla and He, Miao and Palaniswamy, Ramesh and Ramakrishnan, Charu and Ritola, Kimberly and Hantman, Adam and Deisseroth, Karl and Osten, Pavel and Huang, Z Josh and Li, Bo} }