A Neuron-Glial Perspective for Computational Neuroscience

International audienceThere is growing excitement around glial cells, as compelling evidence point to new, previously unimaginable roles for these cells in information processing of the brain, with the potential to affect behavior and higher cognitive functions. Among their many possible functions, glial cells could be involved in practically every aspect of the brain physiology in health and disease. As a result, many investigators in the field welcome the notion of a Neuron-Glial paradigm of brain function, as opposed to Ramon y Cayal's more classical neuronal doctrine which identifies neurons as the prominent, if not the only, cells capable of a signaling role in the brain. The demonstration of a brain-wide Neuron-Glial paradigm however remains elusive and so does the notion of what neuron-glial interactions could be functionally relevant for the brain computational tasks. In this perspective, we present a selection of arguments inspired by available experimental and modeling studies with the aim to provide a biophysical and conceptual platform to computational neuroscience no longer as a mere prerogative of neuronal signaling but rather as the outcome of a complex interaction between neurons and glial cells

Conferring the ability to utilize inorganic polyphosphate on ATP-specific NAD kinase

NAD kinase (NADK) is a crucial enzyme for production of NADP(+). ATP-specific NADK prefers ATP to inorganic polyphosphate [poly(P)] as a phosphoryl donor, whereas poly(P)/ATP-NADK utilizes both ATP and poly(P), and is employed in industrial mass production of NADP(+). Poly(P)/ATP-NADKs are distributed throughout Gram-positive bacteria and Archaea, whereas ATP-specific NADKs are found in Gram-negative α- and γ-proteobacteria and eukaryotes. In this study, we succeeded in conferring the ability to utilize poly(P) on γ-proteobacterial ATP-specific NADKs through a single amino-acid substitution; the substituted amino-acid residue is therefore important in determining the phosphoryl-donor specificity of γ-proteobacterial NADKs. We also demonstrate that a poly(P)/ATP-NADK created through this method is suitable for the poly(P)-dependent mass production of NADP(+). Moreover, based on our results, we provide insight into the evolution of bacterial NADKs, in particular, how NADKs evolved from poly(P)/ATP-NADKs into ATP-specific NADKs