Association of aerobic glycolysis with the structural connectome reveals a benefit–risk balancing mechanism in the human brain

Aerobic glycolysis (AG), that is, the nonoxidative metabolism of glucose, contributes significantly to anabolic pathways, rapid energy generation, task-induced activity, and neuroprotection; yet high AG is also associated with pathological hallmarks such as amyloid-β deposition. An important yet unresolved question is whether and how the metabolic benefits and risks of brain AG is structurally shaped by connectome wiring. Using positron emission tomography and magnetic resonance imaging techniques as well as computational models, we investigate the relationship between brain AG and the macroscopic connectome. Specifically, we propose a weighted regional distance-dependent model to estimate the total axonal projection length of a brain node. This model has been validated in a macaque connectome derived from tract-tracing data and shows a high correspondence between experimental and estimated axonal lengths. When applying this model to the human connectome, we find significant associations between the estimated total axonal projection length and AG across brain nodes, with higher levels primarily located in the default-mode and prefrontal regions. Moreover, brain AG significantly mediates the relationship between the structural and functional connectomes. Using a wiring optimization model, we find that the estimated total axonal projection length in these high-AG regions exhibits a high extent of wiring optimization. If these high-AG regions are randomly rewired, their total axonal length and vulnerability risk would substantially increase. Together, our results suggest that high-AG regions have expensive but still optimized wiring cost to fulfill metabolic requirements and simultaneously reduce vulnerability risk, thus revealing a benefit–risk balancing mechanism in the human brain.

Wiring optimization explanation in neuroscience: What is special about it?

This paper examines the explanatory distinctness of wiring optimization models in neuroscience. Wiring optimization models aim to represent the organizational features of neural and brain systems as optimal (or near-optimal) solutions to wiring optimization problems. My claim is that that wiring optimization models provide design explanations. In particular, they support ideal interventions on the decision variables of the relevant design problem and assess the impact of such interventions on the viability of the target system.

Sloppy morphological tuning in identified neurons of the crustacean stomatogastric ganglion

Neuronal physiology depends on a neuron’s ion channel composition and unique morphology. Variable ion channel compositions can produce similar neuronal physiologies across animals. Less is known regarding the morphological precision required to produce reliable neuronal physiology. Theoretical studies suggest that moraphology is tightly tuned to minimize wiring and conduction delay of synaptic events. We utilize high-resolution confocal microscopy and custom computational tools to characterize the morphologies of four neuron types in the stomatogastric ganglion (STG) of the crab Cancer borealis. Macroscopic branching patterns and fine cable properties are variable within and across neuron types. We compare these neuronal structures to synthetic minimal spanning neurite trees constrained by a wiring cost equation and find that STG neurons do not adhere to prevailing hypotheses regarding wiring optimization principles. In this highly modulated and oscillating circuit, neuronal structures appear to be governed by a space-filling mechanism that outweighs the cost of inefficient wiring.

Neuroanatomy and Cosmology

This article aims to examine the possible relation between neuroanatomy and cosmology. It describes brain-wiring optimization and suggests that such extreme neural network organization is a prerequisite for brain functioning, and it states that it is possible that other set of brain-enabling conditions of the universe exist. It also discusses the relation between brain-wiring minimization and optimization landscapes and between brain-wiring optimization and the anthropic principle.