Energy supply per neuron is constrained by capillary density in the mouse brain.

Neuronal densities vary enormously across sites within a brain. Does the density of the capillary bed vary accompanying the presumably larger energy requirement of sites with more neurons, or with larger neurons, or is energy supply constrained by a mostly homogeneous capillary bed? Here we find evidence for the latter, with a capillary bed that represents typically between 0.7 and 1.5% of the volume of the parenchyma across various sites in the mouse brain, whereas neuronal densities vary by at least 100-fold. As a result, the ratio of capillary cells per neuron decreases uniformly with increasing neuronal density and therefore with smaller average neuronal size across sites. Thus, given the relatively constant capillary density compared to neuronal density in the brain, blood and energy availability per neuron is presumably dependent on how many neurons compete for the limited supply provided by a mostly homogeneous capillary bed. Additionally, we find that local capillary density is not correlated with local synapse densities, although there is a small but significant correlation between lower neuronal density (and therefore larger neuronal size) and more synapses per neuron within the restricted range of 6,500-9,500 across cortical sites. Further, local variations in the glial/neuron ratio are not correlated with local variations in the number of synapses per neuron or local synaptic densities. These findings suggest that it is not that larger neurons, neurons with more synapses, or even sites with more synapses more energy, but simply that larger neurons (in low density sites) have more energy available per cell and for the totality of its synapses than smaller neurons (in high density sites) due to competition for limited resources supplied by a capillary bed of fairly homogeneous density throughout the brain.