Allometric rules for mammalian cortical layer 5 neuron biophysics

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 species 1 – 3 . However, it is unknown whether different species adapt neuronal properties to conserve how single neurons process information 4 – 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. Analyses of layer 5 cortical pyramidal neurons in 10 mammalian species show that human neurons are distinct in that they do not follow the expected allometric relationship between neuron size and membrane conductance.