Functional Implications of the Glia/Neuron Ratio in Vertebrate’s Brain Physiology and Evolution

Glial cells outnumber or equal neurons in many brain regions, and the ratio of glia to neurons (the glia/neuron ratio) is now recognized as a key parameter influencing brain physiology and evolution. Historically, the human brain was erroneously believed to have a glia/neuron ratio of about 10:1, but improved cell counting techniques show roughly a 1:1 overall ratio (von Bartheld et al., 2016). Importantly, this ratio is not constant: it varies widely across species and brain structures in a systematic manner (Herculano-Houzel, 2014). Larger brains and regions with lower neuronal density have higher glia/neuron ratios, reflecting more glial support per neuron (Herculano-Houzel, 2014). Such variations carry significant functional implications. Glial cells – including astrocytes, oligodendrocytes, microglia, and others – play critical roles in metabolic support of neurons, modulation of synaptic activity, maintenance of homeostasis, and immune defense. An increased glia/neuron ratio in certain brains or regions may enhance metabolic capacity, synaptic plasticity, and signaling integration, potentially contributing to cognitive abilities. Conversely, abnormal glia/neuron ratios or dysfunctional glia are linked to neurological and psychiatric diseases, from Alzheimer’s disease to depression. In this article, we review developments since 2014 regarding the functional significance of glia/neuron ratios, focusing on how interspecies and inter-regional differences in this ratio relate to brain metabolism, synaptic function, cognitive processing, and evolution, as well as the emerging evidence of glial involvement in disease. We include comparative analyses across species, discuss evolutionary interpretations of scaling rules, and highlight recent high-impact findings (e.g., human glial cell transplantation enhancing mouse cognition). Visual summaries are provided, including a comparative “dashboard” of glia/neuron ratios across species and brain structures with functional interpretations. Our synthesis underscores that the glia/neuron ratio is not a mere number but a reflection of fundamental design principles of brain architecture, with broad implications for physiology, evolution, and medicine.