Allometric rules for mammalian cortical layer 5 neuron biophysics

Nature. 2021 Dec;600(7888):274-278. doi: 10.1038/s41586-021-04072-3. Epub 2021 Nov 10.


The biophysical properties of neurons are the foundation for computation in the brain. Neuronal size is a key determinant of single neuron input-output features and varies substantially across species1-3. However, it is unknown whether different species adapt neuronal properties to conserve how single neurons process information4-7. Here we characterize layer 5 cortical pyramidal neurons across 10 mammalian species to identify the allometric relationships that govern how neuronal biophysics change with cell size. In 9 of the 10 species, we observe conserved rules that control the conductance of voltage-gated potassium and HCN channels. Species with larger neurons, and therefore a decreased surface-to-volume ratio, exhibit higher membrane ionic conductances. This relationship produces a conserved conductance per unit brain volume. These size-dependent rules result in large but predictable changes in somatic and dendritic integrative properties. Human neurons do not follow these allometric relationships, exhibiting much lower voltage-gated potassium and HCN conductances. Together, our results in layer 5 neurons identify conserved evolutionary principles for neuronal biophysics in mammals as well as notable features of the human cortex.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Biophysics*
  • Cell Size*
  • Cerebral Cortex / anatomy & histology
  • Cerebral Cortex / cytology*
  • Cerebral Cortex / physiology
  • Dendrites / physiology
  • Electric Conductivity
  • Humans
  • Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels / metabolism
  • Male
  • Mammals*
  • Potassium Channels, Voltage-Gated / metabolism
  • Pyramidal Cells / cytology*
  • Pyramidal Cells / physiology*
  • Species Specificity


  • Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels
  • Potassium Channels, Voltage-Gated