Blue Brain builds next-generation models of thalamocortical neurons
The EPFL Blue Brain Project has built the first next-generation models of thalamocortical neurons. These digital models of thalamocortical neurons were built using state-of-the art optimization techniques, which directly constrain unknown parameter values with experimental data. Thalamocortical neurons are essential components in the transmission of information from the outside world to higher order brain areas, such as the neocortex. These neurons fire action potentials in distinct modes, which are associated with different brain states, such as wakefulness and sleep. These findings are the first phase towards the complete modelling of the rodent thalamus, which is the next step for the Blue Brain Project. In addition, the experimental and modelling community can now use these data and models in their analysis and modelling workflows.
Thalamocortical (TC) neurons are one of the main components of the thalamocortical system, which is implicated in key functions including sensory transmission and the transition between brain states. These functions are reflected at the cellular level by the ability to generate action potentials in two distinct modes, called burst and tonic firing. “Capturing the different firing modes of thalamocortical neurons is a key part of our work to understand the cellular and synaptic basis of diverse brain states”, remarks Prof. Sean Hill.
Although the general properties of TC neurons are known, scientists have until now, lacked a detailed characterization of their morphological and electrical properties in the ventrobasal (VB) thalamus. The researchers at Blue Brain began by collecting single cell experimental data from research conducted at the Laboratory of Neural Microcircuitry lab (LNMC) at EPFL. Co-authors at LNMC, Jane Yi and Ying Shi, applied standardized experimental procedures to characterize these neurons, by measuring their 3D shapes and their functional properties. Next the Blue Brain researchers extended existing techniques to capture the multiple firing modes of thalamic neurons. The findings were then compared with additional experimental data, generalization tested and significant deviations from the experimental variability were rejected.
“We built models of these neurons, by using state-of-the art optimisation techniques, which allowed us to directly constrain unknown parameter values with experimental data,” explains Lead Scientist, Elisabetta Iavarone. “The models and their analysis also showed that automatic parameter search can be applied to capture complex firing behavior, such as the co-existence of tonic firing and low-threshold bursting over a wide range of parameter sets and in combination with different neuron morphologies.”
Now the Blue Brain Project and scientists have biophysically detailed models of VB TC neurons that have been explicitly constrained with experimental data from rats and which can be readily integrated in a data-driven pipeline to reconstruct and simulate circuit activity in the thalamocortical system, thereby providing a tool to understand the role of these neurons within the thalamocortical system.
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Iavarone E., Yi J., Shi Y., Zandt B.J., O’Reilly C., Van Geit W., Rössert C., Markram, H., Hill, S.L. (2019) Experimentally-constrained biophysical models of tonic and burst firing modes in thalamocortical neurons. PLOS Computational Biology 15(5): 1-23. e1006753.
Image - Thalamocortical neurons from the sensory thalamus. Three-dimensional reconstructions of neuron morphologies from the sensory thalamus with their electrical properties as recorded in experiments and models.
This study was supported by general funding to the EPFL Blue Brain Project from the Swiss government’s ETH Board of the Swiss Federal Institutes of Technology.