No abstract

The initiation and propagation of action potentials (APs) places high demands on the energetic resources of neural tissue. Each AP forces ATP-driven ion pumps to work harder to restore the ionic concentration gradients, thus consuming more energy. Here, we ask whether the ionic currents underlying the AP can be predicted theoretically from the principle of minimum energy consumption. A long-held supposition that APs are energetically wasteful, based on theoretical analysis of the squid giant axon AP, has recently been overturned by studies that measured the currents contributing to the AP in several mammalian neurons. In the single compartment models studied here, AP energy consumption varies greatly among vertebrate and invertebrate neurons, with several mammalian neuron models using close to the capacitive minimum of energy needed. Strikingly, energy consumption can increase by more than ten-fold simply by changing the overlap of the Na+ and K+ currents during the AP without changing the APs shape. As a consequence, the height and width of the AP are poor predictors of energy consumption. In the Hodgkin–Huxley model of the squid axon, optimizing the kinetics or number of Na+ and K+ channels can whittle down the number of ATP molecules needed for each AP by a factor of four. In contrast to the squid AP, the temporal profile of the currents underlying APs of some mammalian neurons are nearly perfectly matched to the optimized properties of ionic conductances so as to minimize the ATP cost.

Understanding how organisms establish their form during embryogenesis and regeneration represents a major knowledge gap in biological pattern formation. It has been recently suggested that morphogenesis could be understood in terms of cellular information processing and the ability of cell groups to model shape. Here, we offer a proof of principle that self-assembly is an emergent property of cells that share a common (genetic and epigenetic) model of organismal form. This behaviour is formulated in terms of variational free-energy minimization—of the sort that has been used to explain action and perception in neuroscience. In brief, casting the minimization of thermodynamic free energy in terms of variational free energy allows one to interpret (the dynamics of) a system as inferring the causes of its inputs—and acting to resolve uncertainty about those causes. This novel perspective on the coordination of migration and differentiation of cells suggests an interpretation of genetic codes as parametrizing a generative model—predicting the signals sensed by cells in the target morphology—and epigenetic processes as the subsequent inversion of that model. This theoretical formulation may complement bottom-up strategies—that currently focus on molecular pathways—with (constructivist) top-down approaches that have proved themselves in neuroscience and cybernetics.