Scaling of brain metabolism with a fixed energy budget per neuron: implications for neuronal activity, plasticity and evolution

Abstract

It is usually considered that larger brains have larger neurons, which consume more energy individually, and are therefore accompanied by a larger number of glial cells per neuron. These notions, however, have never been tested. Based on glucose and oxygen metabolic rates in awake animals and their recently determined numbers of neurons, here I show that, contrary to the expected, the estimated glucose use per neuron is remarkably constant, varying only by 40% across the six species of rodents and primates (including humans). The estimated average glucose use per neuron does not correlate with neuronal density in any structure. This suggests that the energy budget of the whole brain per neuron is fixed across species and brain sizes, such that total glucose use by the brain as a whole, by the cerebral cortex and also by the cerebellum alone are linear functions of the number of neurons in the structures across the species (although the average glucose consumption per neuron is at least 10× higher in the cerebral cortex than in the cerebellum). These results indicate that the apparently remarkable use in humans of 20% of the whole body energy budget by a brain that represents only 2% of body mass is explained simply by its large number of neurons. Because synaptic activity is considered the major determinant of metabolic cost, a conserved energy budget per neuron has several profound implications for synaptic homeostasis and the regulation of firing rates, synaptic plasticity, brain imaging, pathologies, and for brain scaling in evolution.

Figure 1. Scaling of total glucose use by the whole brain, cerebral cortex and cerebellum.

a, total glucose use by the whole brain (+), cerebral cortex (black circles) and cerebellum (white circles) scales with structure mass raised to similar exponents of 0.873, 0.850 and 0.844. b, total glucose use by the whole brain (+), cerebral cortex (black circles) and cerebellum (white circles) scales with the number of neurons in each structure in a manner that is best described as a linear function. Whole brain: power exponent 0.988, p<0.0001; linear fit, r² = 1.0, p<0.0001. Cerebral cortex: power exponent 0.944, p = 0.0002; linear fit, r² = 1.0, p<0.0001. Cerebellum: power exponent 0.880, p = 0.0001; linear fit, r² = 1.0, p<0.0001.

Figure 2. Scaling of average specific glucose use in the brain and neuronal density.

a, Average glucose use per gram of brain tissue scales linearly with neuronal density. Each point represents the average values for the present species indicated (see Table 1). Average glucose use per gram of brain tissue is best described as a linear function of neuronal density across the species (r2 = 0.906, p = 0.0034), or as a power function of neuronal density with an exponent close to unity (0.986, p = 0.0041). b, Neuronal density in the whole brain varies across the six species in the present sample as a power function of brain mass with an exponent of −0.116 (p = 0.0071). c, Neuronal density in the whole brain is not a universal function of brain mass: while it does not vary significantly with brain mass across insectivores (crosses), it decreases slightly with brain mass raised to an exponent of −0.123 across primates (p = 0.0016, unfilled symbols); more steeply with brain mass raised to an exponent of −0.367 across rodents (p = 0.0011, filled symbols); and with an intermediate exponent of −0.172 across the ensemble of species (p<0.0001). For subsets of mammalian species, the scaling exponent depends on the particular species.