局部谷氨酸介导的树突峰电位改变皮质锥体神经元的状态。

Local glutamate-mediated dendritic plateau potentials change the state of the cortical pyramidal neuron.

机构信息

Institute for Systems Genomics, UConn Health, Farmington, Connecticut.

Department of Physiology and Pharmacology, SUNY Downstate, Brooklyn, New York.

出版信息

J Neurophysiol. 2021 Jan 1;125(1):23-42. doi: 10.1152/jn.00734.2019. Epub 2020 Oct 21.

Abstract

Dendritic spikes in thin dendritic branches (basal and oblique dendrites) are traditionally inferred from spikelets measured in the cell body. Here, we used laser-spot voltage-sensitive dye imaging in cortical pyramidal neurons (rat brain slices) to investigate the voltage waveforms of dendritic potentials occurring in response to spatially restricted glutamatergic inputs. Local dendritic potentials lasted 200-500 ms and propagated to the cell body, where they caused sustained 10- to 20-mV depolarizations. Plateau potentials propagating from dendrite to soma and action potentials propagating from soma to dendrite created complex voltage waveforms in the middle of the thin basal dendrite, comprised of local sodium spikelets, local plateau potentials, and backpropagating action potentials, superimposed on each other. Our model replicated these voltage waveforms across a gradient of glutamatergic stimulation intensities. The model then predicted that somatic input resistance () and membrane time constant (tau) may be reduced during dendritic plateau potential. We then tested these model predictions in real neurons and found that the model correctly predicted the direction of and tau change but not the magnitude. In summary, dendritic plateau potentials occurring in basal and oblique branches put pyramidal neurons into an activated neuronal state ("prepared state"), characterized by depolarized membrane potential and smaller but faster membrane responses. The prepared state provides a time window of 200-500 ms, during which cortical neurons are particularly excitable and capable of following afferent inputs. At the network level, this predicts that sets of cells with simultaneous plateaus would provide cellular substrate for the formation of functional neuronal ensembles. In cortical pyramidal neurons, we recorded glutamate-mediated dendritic plateau potentials with voltage imaging and created a computer model that recreated experimental measures from dendrite and cell body. Our model made new predictions, which were then tested in experiments. Plateau potentials profoundly change neuronal state: a plateau potential triggered in one basal dendrite depolarizes the soma and shortens membrane time constant, making the cell more susceptible to firing triggered by other afferent inputs.

摘要

在薄树突分支(基底和斜树突)中的树突棘通常是从胞体中测量的棘波推断出来的。在这里,我们使用皮质锥体神经元(大鼠脑切片)中的激光点电压敏感染料成像来研究响应空间受限的谷氨酸能输入而发生的树突电位的电压波形。局部树突电位持续 200-500ms,并传播到胞体,在那里它们引起持续的 10-20mV 去极化。从树突传播到胞体的平台电位和从胞体传播到树突的动作电位在薄基底树突的中部产生复杂的电压波形,由局部钠棘波、局部平台电位和逆行动作电位叠加而成。我们的模型在不同的谷氨酸刺激强度梯度上复制了这些电压波形。然后,该模型预测,在树突平台电位期间,体细胞输入电阻()和膜时间常数(tau)可能会降低。然后,我们在真实神经元中测试了这些模型预测,并发现模型正确预测了和 tau 变化的方向,但没有预测到幅度。总之,基底和斜枝中的树突平台电位使锥体神经元进入激活的神经元状态(“准备状态”),其特征是膜电位去极化和较小但更快的膜响应。准备状态提供了 200-500ms 的时间窗口,在此期间,皮质神经元特别容易兴奋并能够跟随传入输入。在网络水平上,这表明同时具有平台的细胞组将为功能性神经元集合体的形成提供细胞基础。在皮质锥体神经元中,我们使用电压成像记录了谷氨酸介导的树突平台电位,并创建了一个计算机模型,该模型从树突和胞体重现了实验测量值。我们的模型提出了新的预测,然后在实验中进行了测试。平台电位深刻地改变了神经元状态:一个基底树突中的平台电位引发去极化,使胞体缩短膜时间常数,使细胞更容易受到其他传入输入触发的放电。

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