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Distinct synaptic plasticity rules operate across dendritic compartments in vivo during learning

Science (New York, N.Y.) 2025年第6744期388卷 322-328页

作者： William J Wright Nathan G Hedrick Takaki Komiyama Department of Neurobiology University of California San Diego La Jolla CA USA. Center for Neural Circuits and Behavior University of California San Diego La Jolla CA USA. Department of Neurosciences University of California San Diego La Jolla CA USA. Halıcıoğlu Data Science Institute University of California San Diego La Jolla CA USA. Kavli Institute for Brain and Mind University of California San Diego La Jolla CA USA.

Synaptic plasticity underlies learning by modifying specific synaptic inputs to reshape neural activity and behavior. However, the rules governing which synapses will undergo different forms of plasticity in vivo during learning and whether these rules are uniform within individual neurons remain unclear. Using in vivo longitudinal imaging with single-synapse resolution in the mouse motor cortex during motor learning, we found that apical and basal dendrites of layer 2/3 (L2/3) pyramidal neurons showed distinct activity-dependent synaptic plasticity rules. The strengthening of apical and of basal synapses is predicted by local coactivity with nearby synapses and activity coincident with postsynaptic action potentials, respectively. Blocking postsynaptic spiking diminished basal synaptic potentiation without affecting apical plasticity. Thus, individual neurons use multiple activity-dependent plasticity rules in a compartment-specific manner in vivo during learning.

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Motor learning refines thalamic influence on motor cortex

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Nature 2025年 1-10页

作者： Ramot, Assaf Taschbach, Felix H. Yang, Yun C. Hu, Yuxin Chen, Qiyu Morales, Bobbie C. Wang, Xinyi C. Wu, An Tye, Kay M. Benna, Marcus K. Komiyama, Takaki Department of Neurobiology University of California San Diego La Jolla CA United States Center for Neural Circuits and Behavior University of California San Diego La Jolla CA United States Department of Neurosciences University of California San Diego La Jolla CA United States Halıcıoğlu Data Science Institute University of California San Diego La Jolla CA United States Salk Institute for Biological Studies Howard Hughes Medical Institute La Jolla CA United States Kavli Institute for the Brain and Mind La Jolla CA United States

The primary motor cortex (M1) is central for the learning and execution of dexterous motor skills1, 2–3, and its superficial layer (layers 2 and 3;hereafter, L2/3) is a key locus of learning-related plasticity1,4, 5–6. It remains unknown how motor learning shapes the way in which upstream regions activate M1 circuits to execute learned movements. Here, using longitudinal axonal imaging of the main inputs to M1 L2/3 in mice, we show that the motor thalamus is the key input source that encodes learned movements in experts (animals trained for two weeks). We then use optogenetics to identify the subset of M1 L2/3 neurons that are strongly driven by thalamic inputs before and after learning. We find that the thalamic influence on M1 changes with learning, such that the motor thalamus preferentially activates the M1 neurons that encode learned movements in experts. Inactivation of the thalamic inputs to M1 in experts impairs learned movements. Our study shows that motor learning reshapes the thalamic influence on M1 to enable the reliable execution of learned movements. © The Author(s), under exclusive licence to Springer Nature Limited 2025.

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Transparent artifact-free graphene electrodes for compact closed-loop optogenetics systems

Transparent artifact-free graphene electrodes for compact cl...

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International Electron Devices Meeting (IEDM)

作者： Xin Liu Yichen Lu Ege Iseri Chi Ren Haixin Liu Takaki Komiyama Duygu Kuzum Department of Electrical and Computer Engineering University of California San Diego USA Center for Neural Circuits and Behavior University of California San Diego La Jolla CA USA University of California San Diego La Jolla CA US

ISBN: (纸本)9781538635605;9781538635599

Graphene offers unique advantages for implantable neural systems by combining properties like optical transparency, flexibility, high conductivity and biocompatibility in a single material. Here we report the first demonstration of a graphene-based compact closed-loop optogenetics system with the capability of recording and processing of neural activity in real time to control the light stimulation. We develop a process flow for high-yield large-area fabrication of transparent graphene microelectrode arrays on clear flexible substrates. Transparent graphene electrodes completely eliminate light-induced artifacts, which hinder the development of compact closed-loop optogenetics systems with conventional metal microelectrodes. We successfully demonstrate closed-loop operation with transparent graphene electrodes for simultaneous optical stimulation and electrical recordings without light artifacts.

关键词： Graphene Microelectrodes Gold Calcium Substrates Biomedical optical imaging

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Selectively driving cholinergic fibers optically in the thalamic reticularnucleus promotes sleep

Selectively driving cholinergic fibers optically in the thal...

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中国睡眠研究会第九届学术年会

作者： Kun-Ming Ni Xiao-Jun Hou Ci-Hang Yang Ping Dong Yue Li Ying Zhang Ping Jiang Darwin K Berg Shumin Duan Xiao-Ming Li Department of Neurobiology Institute of NeuroscienceKey Laboratory of Medical Neurobiology of the Ministry of Health of ChinaCollaborative Innovation Center for Brain ScienceZhejiang University School of Medicine Fuzhou Children's Hospital Neurobiology Section Division of Biological SciencesCenter for Neural Circuits and BehaviorUniversity of California Soft Matter Research Center Zhejiang University

Cholinergic projections from the basal forebrain and brainstem are thought to play important roles in rapid eye movement(REM) sleep and *** transgenic mice in which channelrhdopsin-2 is selectively expressed in cholinergic neurons,we show that optical stimulation of cholinergic inputs to the thalamic reticular nucleus(TRN) activates local GABAergic neurons to promote sleep and protect non-rapid eye movement(NREM) *** does not affect REM ***,direct activation of cholinergic input to the TRN shortens the time to sleep onset and generates spindle oscillations that correlate with NREM *** does so by evoking excitatory postsynaptic currents via a7-containing nicotinic acetylcholine receptors and inducing bursts of action potentials in local GABAergic *** findings stand in sharp contrast to previous reports of cholinergic activity driving *** results provide new insight into the mechanisms controlling sleep.

关键词： Selectively driving cholinergic fibers optically in the thalamic reticularnucleus promotes sleep

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Selectively driving cholinergic fibersoptically in the thalamic reticular nucleuspromotes sleep

Selectively driving cholinergic fibersoptically in the thala...

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第九届海内外华人神经科学家研讨会(The 9th Symposium for Chinese Neuroscientists Worldwide)

作者： Kun-Ming Ni Xiao-Jun Hou Ci-Hang Yang Ping Dong Yue Li Ying Zhang Ping Jiang Darwin K Berg Shumin Duan Xiao-Ming Li Department of Neurobiology Institute of NeuroscienceKey Laboratory of MedicalNeurobiology of the Mi Department of Neurobiology Institute of NeuroscienceKey Laboratory of MedicalNeurobiology of the Mi Neurobiology Section Division ofBiological SciencesCenter for Neural Circuits and BehaviorUniversi Department of Neurobiology Institute of NeuroscienceKey Laboratory of MedicalNeurobiology of the Mi

Cholinergic projections from the basal forebrain and brainstem are thought to play important roles in rapid eye movement(REM)sleep and *** transgenic mice in which channelrhdopsin-2is selectively expressed in cholinergic neurons,we show that optical stimulationof cholinergic inputs to the thalamic reticular nucleus(TRN)activates local GABAergic neurons topromote sleep and protect non-rapid eye movement(NREM)*** does not affect REM ***,direct activation of cholinergic input to the TRN shortens the time to sleep onset andgenerates spindle oscillations that correlate with NREM *** does so by evoking excitatorypostsynaptic currents via a7-containing nicotinic acetylcholine receptors and inducing bursts ofaction potentials in local GABAergic *** findings stand in sharp contrast to previousreports of cholinergic activity driving *** results provide new insight into the mechanismscontrolling sleep.

关键词： Cholinergic neuron The thalamic reticular nucleus Sleep

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Selectively driving cholinergic fibersoptically in the thalamic reticular nucleuspromotes sleep

Selectively driving cholinergic fibersoptically in the thala...

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第九届海内外华人神经科学家研讨会

作者： Kun-Ming Ni Xiao-Jun Hou Ci-Hang Yang Ping Dong Yue Li Ying Zhang Ping Jiang Darwin K Berg Shumin Duan Xiao-Ming Li Department of Neurobiology Institute of Neuroscience Key Laboratory of Medical Neurobiology of the Ministry of Health of China Collaborative Innovation Centerfor Brain Science Zhejiang University School of Medicine Fuzhou Children's Hospital Neurobiology Section Division of Biological Sciences Center for Neural Circuits and Behavior University of California Soft Matter Research Center Zhejiang University

Cholinergic projections from the basal forebrain and brainstem are thought to play important roles in rapid eye movement(REM) sleep and arousal. Using transgenic mice in which channelrhdopsin-2is selectively expressed in cholinergic neurons, we show that optical stimulationof cholinergic inputs to the thalamic reticular nucleus(TRN) activates local GABAergic neurons topromote sleep and protect non-rapid eye movement(NREM) sleep. It does not affect REM ***, direct activation of cholinergic input to the TRN shortens the time to sleep onset andgenerates spindle oscillations that correlate with NREM sleep. It does so by evoking excitatorypostsynaptic currents via a7-containing nicotinic acetylcholine receptors and inducing bursts ofaction potentials in local GABAergic neurons. These findings stand in sharp contrast to previousreports of cholinergic activity driving arousal. Our results provide new insight into the mechanismscontrolling sleep.

关键词： Cholinergic neuron The thalamic reticular nucleus Sleep

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Distinguishing externally from saccade-induced motion in visual cortex (vol 610, pg 135, 2022)

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NATURE 2022年第7934期611卷 E5-E5页

作者： Miura, Satoru K. Scanziani, Massimo Center for Neural Circuits and Behavior Neurobiology Section and Department of Neuroscience University of California San Diego La Jolla CA USA Department of Physiology University of California San Francisco San Francisco CA USA Howard Hughes Medical Institute University of California San Francisco San Francisco CA USA

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Strength in numbersAssociated Content

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Nature 2013年第7433期493卷 482-483页

作者： Morgan Sheng Roberto Malinow Richard Huganir Morgan Sheng is in the Department of Neuroscience Genentech Inc. South San Francisco California 94080 USA. Division of Biology and the Department of Neurosciences Roberto Malinow is in the Center for Neural Circuits and Behavior Neurobiology Section University of California San Diego La Jolla California 92093 USA. Richard Huganir is in the Department of Neuroscience Howard Hughes Medical Institute Johns Hopkins University School of Medicine Baltimore Maryland 21205 USA.

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Partitioning variability in animal behavioral videos using semi-supervised variational autoencoders

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PLoS Computational Biology 2021年第9期17卷 e1009439-e1009439页

作者： Whiteway, Matthew R. Biderman, Dan Friedman, Yoni Dipoppa, Mario Buchanan, E. Kelly Wu, Anqi Zhou, John Bonacchi, Niccolò Miska, Nathaniel J. Noel, Jean-Paul Rodriguez, Erica Schartner, Michael Socha, Karolina Urai, Anne E. Salzman, C. Daniel Cunningham, John P. Paninski, Liam Center for Theoretical Neuroscience Columbia University New YorkNY United States Mortimer B. Zuckerman Mind Brain Behavior Institute Columbia University New YorkNY United States Grossman Center for the Statistics of Mind Columbia University New YorkNY United States Department of Statistics Columbia University New YorkNY United States Department of Neuroscience Columbia University New YorkNY United States Department of Brain and Cognitive Sciences Massachusetts Institute of Technology BostonMA United States Department of Computer Science Columbia University New YorkNY United States Champalimaud Centre for the Unknown Lisbon Portugal Sainsbury-Wellcome Centre for Neural Circuits and Behavior University College London London United Kingdom Center for Neural Science New York University New YorkNY United States Institute of Ophthalmology University College London London United Kingdom Cognitive Psychology Unit Leiden University Leiden Netherlands Department of Psychiatry Columbia University New YorkNY United States New York State Psychiatric Institute New YorkNY United States Kavli Institute for Brain Sciences New YorkNY United States

Recent neuroscience studies demonstrate that a deeper understanding of brain function requires a deeper understanding of behavior. Detailed behavioral measurements are now often collected using video cameras, resulting in an increased need for computer vision algorithms that extract useful information from video data. Here we introduce a new video analysis tool that combines the output of supervised pose estimation algorithms (e.g. DeepLabCut) with unsupervised dimensionality reduction methods to produce interpretable, low-dimensional representations of behavioral videos that extract more information than pose estimates alone. We demonstrate this tool by extracting interpretable behavioral features from videos of three different head-fixed mouse preparations, as well as a freely moving mouse in an open field arena, and show how these interpretable features can facilitate downstream behavioral and neural analyses. We also show how the behavioral features produced by our model improve the precision and interpretation of these downstream analyses compared to using the outputs of either fully supervised or fully unsupervised methods alone. Copyright: © 2021 Whiteway et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

关键词： Video cameras

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Loss of MeCP2 in cholinergic neurons causes part of RTT-like phenotypes via α7 receptor in hippocampus

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Cell research 2016年第6期26卷 728-42页

作者： Ying Zhang Shu-Xia Cao Peng Sun Hai-Yang He Ci-Hang Yang Xiao-Juan Chen Chen-Jie Shen Xiao-Dong Wang Zhong Chen Darwin K Berg Shumin Duan Xiao-Ming Li Department of Neurobiology Institute of Neuroscience Key Laboratory of Medical Neurobiology of the Ministry of Health of China Collaborative Innovation Center for Brain Science Zhejiang University School of Medicine Hangzhou Zhejiang 310058 China. Neurobiology Section Division of Biological Sciences and Center for Neural Circuits and Behavior University of California San Diego La Jolla CA 92093-0357 USA. Soft Matter Research Center Zhejiang University Hangzhou Zhejiang China.

Mutations in the X-linked MECP2 gene cause Rett syndrome (RTT), an autism spectrum disorder characterized by impaired social interactions, motor abnormalities, cognitive defects and a high risk of epilepsy. Here, we showed that conditional deletion of Mecp2 in cholinergic neurons caused part of RTT-like phenotypes, which could be rescued by re-expressing Mecp2 in the basal forebrain (BF) cholinergic neurons rather than in the caudate putamen of conditional knockout (Chat-Mecp2(-/y)) mice. We found that choline acetyltransferase expression was decreased in the BF and that α7 nicotine acetylcholine receptor signaling was strongly impaired in the hippocampus of Chat-Mecp2(-/y) mice, which is sufficient to produce neuronal hyperexcitation and increase seizure susceptibility. Application of PNU282987 or nicotine in the hippocampus rescued these phenotypes in Chat-Mecp2(-/y) mice. Taken together, our findings suggest that MeCP2 is critical for normal function of cholinergic neurons and dysfunction of cholinergic neurons can contribute to numerous neuropsychiatric phenotypes.

关键词： MeCP2 cholinergic system Rett syndrome RTT-like phenotypes

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