Cellular and Synaptic Diversity of Layer 2-3 Pyramidal Neurons in Human Individuals

Understanding the functional principles of the human brain requires deep insight into the neuronal and network physiology. To what extent such principles of cellular physiology and synaptic interactions are common across different human individuals is unknown. We characterized the physiology of ~1200 pyramidal neurons and ~1400 monosynaptic connections using advanced multineuron patch-clamp recordings in slices from human temporal cortex. To disentangle within and between individual sources of heterogeneity, we recorded up to 100 neurons per single subject. We found that neuronal, but not synaptic physiology varied with laminar depth. Connection probability was ~15% throughout layer 2-3. Synaptic amplitudes exhibited heavy-tailed distributions with an inverse power law relationship to short term plasticity. Neurons could be classified into four functional subtypes. These general principles of microcircuit physiology were common across individuals. Our study advances the understanding of human neuron and synaptic diversity from an individual and phenotypic perspective.