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Reexamining the Role of Dendrites in Neuronal Function

重新审视树突在神经元功能中的作用

基本信息

批准号：
10721626
负责人：
Jayeeta Basu
金额：
$ 268.12万
依托单位：
COLUMBIA UNIV NEW YORK MORNINGSIDE
依托单位国家：
美国
项目类别：
财政年份：
2023
资助国家：
美国
起止时间：
2023-08-01 至 2028-07-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10721626
关键词：
3-Dimensional Action Potentials Affect Anatomy Axon Biophysical Process Brain Calibration Cells Communities Computer Models Computing Methodologies Data Data Set Dendrites Dendritic Spines Development Dimensions Disease Elements Engineering Excitatory Postsynaptic Potentials Future Generations Goals Holography Image In Vitro Inhibitory Synapse Laboratories Logic Maps Measurement Measures Mediating Mental disorders Methods Microscopy Modeling Molecular Morphology Mus Neurons Neurosciences Outcome Output Pathologic Play Pyramidal Cells Research Research Personnel Resolution Role Sensory Series Site Structure Synapses Synaptic Potentials Testing Textbooks Tissues Trees Vertebral column Visual Cortex WFS1 gene Work analog area striata biophysical analysis cell type design experimental study hippocampal pyramidal neuron improved in vivo knowledge graph nervous system disorder network models neuronal cell body novel optogenetics patch clamp phenomenological models public database reconstruction response screening synergism two-photon ultra high resolution voltage

项目摘要

The textbook model of a neuron is one where dendrites merely serve as recipients of excitatory or inhibitory synaptic inputs, integrated at the soma to generate action potentials. However, dendrites generate local spikes that could be critical nonlinear decision points, and recent data suggest that excitatory inputs may only have an effect in the neuronal output if they are activated together in clusters, triggering dendritic spikes. We want to re-examine the role of dendrites in neuronal function in vivo and help usher in, a new “dendrocentric” paradigm of how neurons work, as opposed to the current “somacentric” one. To bring this change, we will assemble a “Dendrite Consortium” of complementary laboratories, expert in genetically-encoded voltage indicators, volumetric two-photon imaging, holographic optogenetics and optochemistry, dendritic patching, EM connectomics, superresolution synaptic mapping and computational models. Wwe will use holographic optogenetics to activate dendritic spines in arbitrary patters (as if one were “playing the piano”), while imaging voltage in 3D with new GEVIs in dendrites from a subtype of L2/3 pyramidal neuron from mouse visual cortex in vivo during sensory stimulation and spontaneous activity, combining this with direct patch recordings from dendrites. These experiments will characterize the functional regimes that generate dendritic spikes in vivo and elucidate their biophysical mechanisms and overall impact on somatic spiking. We will then use connectomics and expansion microscopy to reconstruct complete morphologies and synapse compositions of these dendrites, including imaged ones. These combined functional and structural data will be used to build a rigorous computational model of the neurons, where the functional and computational roles of dendritic spikes will be explored numerically and systematically. Through a collective, integrated effort, we will elucidate the computational logic and functional roles of dendrites and help usher in a new working model of a neuron. We will also generate for the field open-access morphological, functional and computational datasets of complete dendritic trees from one pyramidal neuron subtype, activated by sensory stimulation or intracortical activity. These datasets, including “Rosetta” ones of the same exact neuron, could enable answers to outstanding basic questions on dendritic function in normal and pathological states, as dendrites are central functional elements in all brain circuits and are affected in many neurological and mental disorders.

在教科书中，神经元的模型是树突仅仅作为接收信号的细胞