Of mice and men: topologically complex dendrites assemble uniquely human networks

Abstract

AbstractThe organizational principles that distinguish the human brain from other species have been a long-standing enigma in neuroscience. Focusing on the uniquely evolved cortical layers 2 and 3 in human, human pyramidal neurons show more intense connectivity among themselves compared to the mouse. This is surprising because human L2 and 3 neurons are much sparser. We show that the number and size of neuronsper sefail to account for this connectivity difference, suggesting that another property of neurons is key in determinant of human network connectivity. Topological comparison of dendritic structure reveals much higher perisomatic (basal and oblique) branching density in human pyramidal cells. Using topological tools we quantitatively show that this cellular-level structural property directly impacts network-level topological complexity, including the formation of a rich subnetwork structure. We conclude that greater dendritic complexity, which is a defining attribute of human L2 and 3 neurons, may provide enhanced computational capacity and cognitive flexibility to the human cortex.Graphical abstractA. Multiscale analysis was performed to compare the mouse and human brains: from the anatomical properties of brain regions to the morphological details of single neurons. B. Human circuits are larger than mice in terms of size and number of neurons, but present descreased neuron density, resulting in increased distances between neurons, particularly among pyramidal cells. C. Greater network complexity emerges within the human brain. Network complexity is defined by larger groups of neurons forming complex interconnections throughout the network. D. The topological analysis of layer 2/3 pyramidal cells in the cortex reveals an intriguing difference: human neurons exhibit a significantly larger number of dendritic branches, especially near the cell body compared to mice. This phenomenon is termed “ higher topological complexity” in dendrites. Our findings suggest that dendritic complexity wields a more substantial influence on network complexity than neuron density does, hinting at a potential strategy for enhancing cognitive abilities.