The differential gene expression of brain areas explains the generation of complex neural dynamics

A study led by Gustavo Deco, ICREA research professor and director of the Center for Brain and Cognition, in collaboration with Morten L. Kringelbach, a researcher at the universities of Oxford (UK) and Aarhus (Denmark), together with researchers from the Max Planck Institute and several centres in Australia, published on 14 July in Science Advances.

Brain regions vary in their molecular and cellular composition , but how this heterogeneity shapes neuronal dynamics is unclear. Ideally, one could model regional heterogeneity using empirically observed estimates of areal variations in excitatory and inhibitory cell counts or a related measure of cell type-specific activity. A group of researchers has studied the dynamical consequences of regional heterogeneity using a biophysical model of whole-brain functional magnetic resonance imaging (MRI) dynamics in humans.

Gustavo Deco , ICREA research professor at the UPF Department of Information and Communication Technologies ( DTIC ) and director of the Center for Brain and Cognition ( CBC ), is the first author of a paper published in the journal Science Advances on 14 July explaining this research. The study was conducted together with Morten L. Kringelbach , a researcher at the universities of Oxford (UK) and Aarhus (Denmark), researchers at the Max Planck Institute and also involved the participation of centres in Australia.

The study identifies the key role of transcriptional variations in excitatory and inhibitory receptor (E:I) gene expression in the generation of complex neuronal dynamics

At first, biophysical models of large-scale brain activity treated all local population dynamics as homogeneous, driven by subpopulations of inhibitory and excitatory neurons with uniform properties across all brain regions. However, for more than a century, heterogeneity in regional cytoarchitecture has been noted and subsequent work has provided mounting evidence for large-scale cortical gradients in gene expression, cellular composition, connectivity, and function. Thus, quantitative variations of local circuit properties across the cortex also play an important role in shaping complex neural dynamics, likely through their influence on the local ratio, or balance, of excitatory and inhibitory cell activity.

The authors of this paper present a model that uses transcriptional data of the whole brain to restrict regional heterogeneity and adjust the dynamics of each region according to specific regional measures of gene expression of inhibitor and excitatory receptors.

"We show how models in which transcriptional variations in excitatory and inhibitory receptor (E:I) gene expression constrain regional heterogeneity more accurately reproduce the spatiotemporal structure of empirical functional connectivity estimates than do models constrained by global gene expression profiles or MRI-derived estimates of myeloarchitecture", Deco points out in his work.

And he adds: "Moreover, we show that regional transcriptional heterogeneity is essential for yielding both ignition-like dynamics, which are thought to support conscious processing , and a wide variance of regional-activity time scales, which supports a broad dynamical range". Therefore, in their article the authors identify a key role for E:I heterogeneity in generating complex neuronal dynamics and demonstrate the viability of using transcriptomic data to constrain models of large-scale brain function.

Reference work:

Gustavo Deco, Morten L. Kringelbach, Aurina Arnatkeviciute, Stuart Oldham , Kristina Sabaroedin, Nigel C. Rogasch, Kevin M. Aquino, Alex Fornito (2021), " Dynamical consequences of regional heterogeneity in the brain’s transcriptional landscape ", Science Advances, 14 de juliol. DOI: 10.1126/sciadv.abf4752

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