Creation of Neuronal Ensembles and Cell-Specific Homeostatic Plasticity through Chronic Sparse Optogenetic Stimulation
Creation of Neuronal Ensembles and Cell-Specific Homeostatic Plasticity through Chronic Sparse Optogenetic Stimulation
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DOI：
10.1523/jneurosci.1104-22.2022
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发表时间：
2023-01-04
影响因子：
5.3
通讯作者：
Buonomano, Dean V.
中科院分区：
文献类型：
--
作者：
Liu, Benjamin;Seay, Michael J.;Buonomano, Dean V.
皮质计算来自嵌入复杂皮质回路中的神经元的动力学。在这些电路中，具有共同功能连接性的子网的神经元合奏以经验依赖的方式出现。在这里，我们通过通过慢性光遗传学刺激差异地激活亚群，从而引起了两性小鼠的离体皮质回路中的集合。我们观察到电压相关性的降低，重要的是刺激和未刺激的种群之间的突触脱钩。我们还观察到在刺激人群中的起伏期间发射速率下降。这些集合特异性的变化伴随着刺激人群中内在兴奋性的降低，以及刺激和未刺激的锥体神经元之间的连通性降低。通过将内在兴奋性和连接性的经验观察到的变化纳入尖峰神经网络模型，我们能够证明内在兴奋性和连通性的变化构成了触发速率的降低，但仅涉及观察到的去相关的连接性变化。我们的发现有助于确定慢性图案刺激能力在皮质回路内创建合奏的能力的机制，并且重要的是，尽管Up-States是一种全球范围内的网络范围范围的现象，但功能上不同的合奏可以通过差异率和相关性来维护其身份。
Cortical computations emerge from the dynamics of neurons embedded in complex cortical circuits. Within these circuits, neuronal ensembles, which represent subnetworks with shared functional connectivity, emerge in an experience-dependent manner. Here we induced ensembles in ex vivo cortical circuits from mice of either sex by differentially activating subpopulations through chronic optogenetic stimulation. We observed a decrease in voltage correlation, and importantly a synaptic decoupling between the stimulated and nonstimulated populations. We also observed a decrease in firing rate during Upstates in the stimulated population. These ensemble-specific changes were accompanied by decreases in intrinsic excitability in the stimulated population, and a decrease in connectivity between stimulated and nonstimulated pyramidal neurons. By incorporating the empirically observed changes in intrinsic excitability and connectivity into a spiking neural network model, we were able to demonstrate that changes in both intrinsic excitability and connectivity accounted for the decreased firing rate, but only changes in connectivity accounted for the observed decorrelation. Our findings help ascertain the mechanisms underlying the ability of chronic patterned stimulation to create ensembles within cortical circuits and, importantly, show that while Up-states are a global network-wide phenomenon, functionally distinct ensembles can preserve their identity during Up-states through differential firing rates and correlations.