期刊
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
卷 117, 期 17, 页码 9554-9565出版社
NATL ACAD SCIENCES
DOI: 10.1073/pnas.2000671117
关键词
modeling; basal ganglia; network; compartmental models; computational analysis
资金
- Swedish Medical Research Council [VR-M-K2013-62X-03026, VR-M-2015-02816, VR-M-2018-02453, VR-M-2017-02806, VR-M 2015-02403]
- European Union [604102, FP7/2007-2013]
- EU/Horizon 2020 [720270, 785907]
- National Institute on Alcohol Abuse and Alcoholism [2R01AA016022]
- Knut & Alice Wallenberg Foundation [KAW 2014.0051]
- European Research Council [ERC 282012]
- Swedish Brain Foundation [FO2018-0107]
- Karolinska Institutet Strategic Program for Neuroscience
- Karolinska Institutet doctoral fund
- Karolinska Institutet
The basal ganglia play an important role in decision making and selection of action primarily based on input from cortex, thalamus, and the dopamine system. Their main input structure, striatum, is central to this process. It consists of two types of projection neurons, together representing 95% of the neurons, and 5% of interneurons, among which are the cholinergic, fast-spiking, and low threshold-spiking subtypes. The membrane properties, somadendritic shape, and intrastriatal and extrastriatal synaptic interactions of these neurons are quite well described in the mouse, and therefore they can be simulated in sufficient detail to capture their intrinsic properties, as well as the connectivity. We focus on simulation at the striatal cellular/microcircuit level, in which the molecular/subcellular and systems levels meet. We present a nearly full-scale model of the mouse striatum using available data on synaptic connectivity, cellular morphology, and electrophysiological properties to create a microcircuit mimicking the real network. A striatal volume is populated with reconstructed neuronal morphologies with appropriate cell densities, and then we connect neurons together based on appositions between neurites as possible synapses and constrain them further with available connectivity data. Moreover, we simulate a subset of the striatum involving 10,000 neurons, with input from cortex, thalamus, and the dopamine system, as a proof of principle. Simulation at this biological scale should serve as an invaluable tool to understand the mode of operation of this complex structure. This platform will be updated with new data and expanded to simulate the entire striatum.
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