Biology subjects

Mertens, E. J.

Publications and source records attributed to Mertens, E. J..

5 recordsLinked to original sources

bioRxiv2025

Human neurons undergo protracted functional maturation into adulthood

Summary ParagraphHuman cognitive development is uniquely prolonged1-3, reflecting the extended postnatal maturation of the cerebral cortex where cell-type differentiation4,5, synaptogenesis6,7, myelination8 and transcriptional regulation5,9,10 all follow protracted developmental timelines. However, when human cortical neurons reach functional electrophysiological maturity and how their developmental trajectory compares to other species remains unknown. Here we show through patch-clamp recordings of human temporal cortex from infancy to adulthood that supragranular pyramidal neurons exhibit pronounced neoteny of their functional properties, with physiological maturation continuing well into adulthood. Comparing human and mouse developmental trajectories reveals human neurons are on a much slower developmental timeline, maturing physiologically hundreds of times slower than mouse and 2-6 times slower than would be predicted from anatomical brain growth differences between species. This reflects a fundamentally different allometric relationship between physiological and anatomical maturation; while mouse neuronal physiology closely tracks brain growth, human physiological development follows its own extended timeline. This slow maturation results in different stages of cognitive development being supported by functionally distinct neuronal populations, with the progression from infancy to middle age characterized by specific electrophysiological profiles. Notably, a neuronal subtype thought to be human-specific, with electrophysiological traits that enhance computational capacity, appears only in late adolescence or early adulthood. This extreme protraction of neurophysiological development provides a cellular basis for prolonged human cognitive maturation, demonstrating that neuronal physiological neoteny represents a fundamental evolutionary adaptation in human brain development.

neuroscience↗

bioRxiv2023

Of mice and men: Increased dendritic complexity gives rise to unique human networks

The organizational principles that distinguish the human brain from other species have been a long-standing enigma in neuroscience. Focusing on the uniquely evolved human cortical layers 2 and 3, we computationally reconstruct the cortical architecture for mice and humans. We show that human pyramidal cells form highly complex networks, demonstrated by the increased number and simplex dimension compared to mice. This is surprising because human pyramidal cells are much sparser in the cortex. We show that the number and size of neurons fail to account for this increased network complexity, suggesting that another morphological property is a key determinant of 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 neuronal structural property directly impacts network complexity, including the formation of a rich subnetwork structure. We conclude that greater dendritic complexity, a defining attribute of human L2 and 3 neurons, may provide the human cortex with enhanced computational capacity and cognitive flexibility. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=100 SRC="FIGDIR/small/557170v3_ufig1.gif" ALT="Figure 1"> View larger version (22K): org.highwire.dtl.DTLVardef@c0adadorg.highwire.dtl.DTLVardef@1ca4aaeorg.highwire.dtl.DTLVardef@1ecf1b5org.highwire.dtl.DTLVardef@f0d44d_HPS_FORMAT_FIGEXP M_FIG C_FIG A. A 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 decreased 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 temporal 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.

neuroscience↗

bioRxiv2022

Human voltage-gated Na+ and K+ channel properties underlie sustained fast AP signaling

Human cortical pyramidal neurons are large, have extensive dendritic trees, and yet have surprisingly fast input-output properties: rapid subthreshold synaptic membrane potential changes are reliably encoded in timing of action potentials (APs). Here, we tested whether biophysical properties of voltage-gated sodium (Na+) and potassium (K+) currents in human pyramidal neurons can explain their fast input-output properties. Human Na+ and K+ currents exhibited more depolarized voltage-dependence, slower inactivation and faster recovery from inactivation compared with their mouse counterparts. Computational modeling showed that despite lower Na+ channel densities in human neurons, the biophysical properties of Na+ channels resulted in higher channel availability and contributed to fast AP kinetics stability. Finally, human Na+ channel properties also resulted in a larger dynamic range for encoding of subthreshold membrane potential changes. Thus, biophysical adaptations of voltage-gated Na+ and K+ channels enable fast input-output properties of large human pyramidal neurons. One-Sentence SummaryBiophysical properties of Na+ and K+ ion channels enable human neurons to reliably encode fast inputs into output.

neuroscience↗

bioRxiv2022

Structural and functional specializations of human fast spiking neurons support fast cortical signaling

Fast spiking interneurons (FSINs) provide fast inhibition that synchronizes neuronal activity and is critical for cognitive function. Fast synchronization frequencies are evolutionary conserved in the expanded human neocortex, despite larger neuron-to-neuron distances that challenge fast input-output transfer functions of FSINs. Here, we test in human neurons from neurosurgery tissue which mechanistic specializations of human FSINs explain their fast-signaling properties in human cortex. With morphological reconstructions, multi-patch recordings, and biophysical modeling we find that despite three-fold longer dendritic path, human FSINs maintain fast inhibition between connected pyramidal neurons through several mechanisms: stronger synapse strength of excitatory inputs, larger dendrite diameter with reduced complexity, faster AP initiation, and faster and larger inhibitory output, while Na+ current activation/inactivation properties are similar. These adaptations underlie short input-output delays in fast inhibition of human pyramidal neurons through FSINs, explaining how cortical synchronization frequencies are conserved despite expanded and sparse network topology of human cortex. Teaser/one-sentence summarySpecializations of fast spiking human neurons ensure fast signaling in human cortex.

neuroscience↗

bioRxiv2021

Expansion of cortical layers 2 and 3 in human left temporal cortex associates with verbal intelligence

The expansion of supragranular cortical layers is thought to have enabled evolutionary development of human cognition and language. However, whether increased volume of supragranular cortical layers can actually support greater cognitive and language abilities in humans has not been demonstrated. Here, we find that subjects with higher general and verbal intelligence test (VIQ) scores have selectively expanded layers 2 and 3 only in the left temporal cortex, an area associated with language and IQ-test performance. This expansion is accompanied by lower neuron densities and larger cell-body size. Furthermore, individuals with higher VIQ scores had neurons with larger dendritic trees in left temporal cortex, potentially impacting their function. Indeed, neurons of subjects with higher VIQ scores had faster action potential upstroke kinetics, which improves information processing. These data show that expansion of supragranular layer volume, cortical and cellular micro-architecture and function are associated with improved verbal mental ability in human subjects.

neuroscience↗