Reexamining the Role of Dendrites in Neuronal Function

神经元的教科书模型是树突仅仅作为 兴奋性或抑制性突触输入，整合在索马以产生动作 潜力然而，树突产生的局部尖峰可能是临界非线性的， 决策点，最近的数据表明，兴奋性输入可能只在 神经元输出，如果它们在集群中被激活，触发树突棘波。 我们希望重新研究树突在体内神经元功能中的作用， 在，一个新的“树木中心”的神经元如何工作的范例，而不是目前的 “体细胞中心”1。为了实现这一变化，我们将组建一个“树枝状联盟”， 互补实验室，基因编码电压指示器专家，体积 双光子成像，全息光遗传学和光化学，树突修补， EM连接组学，超分辨率突触映射和计算模型。WWE 将使用全息光遗传学来激活任意模式的树突棘（就像 一个是“弹钢琴”），而在树突中用新的GEVI在3D中成像电压 来自小鼠体内视皮层的L2/3锥体神经元亚型， 感觉刺激和自发活动，将其与直接贴片记录相结合 从树突。这些实验将描述产生的功能机制， 树突棘在体内，并阐明其生物物理机制和整体影响 关于躯体刺激然后，我们将使用连接组学和扩展显微镜， 重建这些树突的完整形态和突触组成， 包括成像的。这些组合的功能和结构数据将用于 建立一个严格的神经元计算模型，其中的功能和 本文将对树突棘波的计算作用进行系统的数值研究。 通过集体的、综合的努力，我们将阐明计算逻辑， 树突的功能作用，并帮助引入一个新的神经元工作模型。我们将 还生成该领域的开放获取形态，功能和计算 来自一种锥体神经元亚型的完整树突树的数据集，由 感觉刺激或皮质内活动。这些数据集，包括“罗塞塔”的数据集， 同样的神经元，可以回答悬而未决的基本问题， 树突在正常和病理状态下的功能，因为树突是中枢功能 所有大脑回路中的元素，并在许多神经和精神疾病的影响。

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.