Lausanne: Scientists have created the first computer model of the metabolic coupling between neuron and glia, an essential feature of brain function. Confirming previous experimental data, the model is now being integrated into the brain modeling efforts developed by the Blue Brain Project.
The brain uses glucose for energy in a very
efficient manner. However, given the brain’s structure and metabolic
constraints, the way it achieves this efficiency is a mystery. The key
is the little-understood relationship between neurons, blood vessels and
the other cells of the brain, the glia. Scientists at École
Polytechnique Fédérale de Lausanne (EPFL) and the King Abdullah
University of Science and Technology (KAUST) have now developed the
first computer model of this relationship, which has successfully
matched previous experimental in vivo and in vitro data in the field.
The model, published in PLOS Computational Biology, is now being integrated into the detailed brain model of the Blue Brain Project.
brain is more than neurons passing information between them. Over half
of the brain is actually composed by glial cells, which support and
insulate neurons, supply them with energy substrates, protect them from
pathogens and even clear out dead neurons from the brain. In fact, glial
cells, neurons and the brain’s blood vessels form a functional unit,
the neuron-glia-vascular unit (NGV) that regulates the brain’s energy
A team led by Pierre Magistretti (EPFL, KAUST),
working with Renaud Jolivet (University College London), has now
developed a detailed computer model that accurately captures the
dynamics of this relationship. Specifically, the model shows how glucose
is shuttled between the three elements of the unit to produce energy
for activated neurons.
Previous experiments from Magistretti’s
group show that glucose flows from a type of glia cells called
“astrocytes” to neurons in the form of lactate. However, some
theoretical studies have proposed that lactate could go the other way –
from neurons to astrocytes. This has major implications for our
understanding of brain energy metabolism.
The model has now
confirmed in quantitative terms that lactate flows from astrocytes to
neurons. It is also the first such model to successfully simulate the
actual timeframe of this process, a breakthrough that provides a
measurable picture of how neurons and glial cells tightly coordinate
brain energy metabolism.
A better understanding of the metabolic
relationships between neurons and glia has also important implications
for understanding the signals detected with functional brain imaging
techniques, such as fMRI and PET, which monitor glucose utilization,
blood flow or oxygen consumption changes that occur in register with
“This is the first time-dependent and
multi-scale model of the neuron-glia-blood vessel that accurately
reflects experimental observations from multiple cells types and
organisms,” says Pierre Magistretti. The model is now being integrated
with the accurate brain model being developed by the Blue Brain Project
at EPFL. “By adding the extra layer of neuron-glial dynamics, we can
take a step toward more accurately modeling the real working of the
This work represents a collaboration of EPFL with the
University College London, and King Abdullah University of Science and
Technology (KAUST). It was partly supported by a grant from KAUST for a
collaboration between the Blue Brain Project at EPFL and the KAUST-EPFL
Alliance for Neuro-inspired High Performance Computing.
Jolivet R, Coggan JS, Allaman I, Magistretti PJ. Multi-timescale Modeling of Activity-Dependent Metabolic Coupling in the Neuron-Glia-Vasculature Ensemble. PLOS Computational Biology 26 February 2015. DOI: 10.1371/journal.pcbi.1004036