Accelerated signal propagation speed in human neocortical microcircuits

Human-specific cognitive abilities depend on information processing in the cerebral cortex, where neurons are significantly larger and sparser compared to rodents. We found that, in synaptically-connected layer 2/3 pyramidal cells (L2/3 PCs), soma-to-soma signal propagation delay is similar in humans and rodents. Thus, to compensate for the increase in neurons’ size, membrane potential changes must propagate faster in human axons and/or dendrites. Dual somato-dendritic and somato-axonal patch recordings show that action potentials (APs) propagation speed is similar in human and rat axons, but the forward propagation of the EPSPs and the back-propagating APs are ∼1.7-fold faster in human dendrites. Faithful biophysical models of human and rat L2/3 PCs, combined with pharmacological manipulations of membrane properties, showed that the larger dendritic diameter, combined with differences in cable properties, underlie the accelerated signal propagation in human cortical circuits. The implication for information processing in the human brain are discussed. Teaser Large human cortical neurons increase dendrite diameter and signal propagation speed for fast cell-to-cell communication.

[1]  H. Mansvelder,et al.  Evolution of cortical neurons supporting human cognition , 2022, Trends in Cognitive Sciences.

[2]  H. Markram,et al.  Strong and reliable synaptic communication between pyramidal neurons in adult human cerebral cortex , 2022, Cerebral cortex.

[3]  H. S. Meyer,et al.  Connectomic comparison of mouse and human cortex , 2022, Science.

[4]  Mark T. Harnett,et al.  Allometric rules for mammalian cortical layer 5 neuron biophysics , 2021, Nature.

[5]  Brian R. Lee,et al.  Human neocortical expansion involves glutamatergic neuron diversification , 2021, Nature.

[6]  Staci A. Sorensen,et al.  Local Connectivity and Synaptic Dynamics in Mouse and Human Neocortex , 2021, bioRxiv.

[7]  M. Häusser,et al.  Are Human Dendrites Different? , 2020, Trends in Cognitive Sciences.

[8]  K. Zaghloul,et al.  Activity-dependent tuning of intrinsic excitability in mouse and human neurogliaform cells , 2020, bioRxiv.

[9]  Kareem A. Zaghloul,et al.  Replay of cortical spiking sequences during human memory retrieval , 2020, Science.

[10]  M. Larkum,et al.  Dendritic action potentials and computation in human layer 2/3 cortical neurons , 2020, Science.

[11]  Jan Born,et al.  Mechanisms of systems memory consolidation during sleep , 2019, Nature Neuroscience.

[12]  T. Bliss,et al.  Persistent memories of long-term potentiation and the N-methyl-d-aspartate receptor , 2019, Brain and neuroscience advances.

[13]  Dominique Debanne,et al.  Plasticity of intrinsic neuronal excitability , 2019, Current Opinion in Neurobiology.

[14]  Huibert D Mansvelder,et al.  Synaptic plasticity in human cortical circuits: cellular mechanisms of learning and memory in the human brain? , 2019, Current Opinion in Neurobiology.

[15]  Trygve E Bakken,et al.  h-Channels Contribute to Divergent Intrinsic Membrane Properties of Supragranular Pyramidal Neurons in Human versus Mouse Cerebral Cortex , 2018, Neuron.

[16]  Human Cortical Dendrites: Stretched to Perform Better? , 2018, Cell.

[17]  Mark T. Harnett,et al.  Enhanced Dendritic Compartmentalization in Human Cortical Neurons , 2018, Cell.

[18]  Bernd Kuhn,et al.  Simultaneous dendritic voltage and calcium imaging and somatic recording from Purkinje neurons in awake mice , 2018, Nature Communications.

[19]  Michele Giugliano,et al.  Large and fast human pyramidal neurons associate with intelligence , 2018, bioRxiv.

[20]  Richard H Scheuermann,et al.  Transcriptomic and morphophysiological evidence for a specialized human cortical GABAergic cell type , 2017, Nature Neuroscience.

[21]  Idan Segev,et al.  Comprehensive Morpho-Electrotonic Analysis Shows 2 Distinct Classes of L2 and L3 Pyramidal Neurons in Human Temporal Cortex , 2017, Cerebral cortex.

[22]  Gábor Tamás,et al.  Identified Cellular Correlates of Neocortical Ripple and High-Gamma Oscillations during Spindles of Natural Sleep , 2016, Neuron.

[23]  G. Tamás,et al.  Plasticity in Single Axon Glutamatergic Connection to GABAergic Interneurons Regulates Complex Events in the Human Neocortex , 2016, PLoS biology.

[24]  Guy Eyal,et al.  Unique membrane properties and enhanced signal processing in human neocortical neurons , 2016, eLife.

[25]  Márton Rózsa,et al.  Human pyramidal to interneuron synapses are mediated by multi-vesicular release and multiple docked vesicles , 2016, eLife.

[26]  Nicholas G Hatsopoulos,et al.  High-frequency oscillations in human and monkey neocortex during the wake–sleep cycle , 2016, Proceedings of the National Academy of Sciences.

[27]  Idan Segev,et al.  A theoretical view of the neuron as an input–output computing device , 2016 .

[28]  G. Buzsáki.  Hippocampal sharp wave‐ripple: A cognitive biomarker for episodic memory and planning , 2015, Hippocampus.

[29]  Guy Eyal,et al.  Dendritic and Axonal Architecture of Individual Pyramidal Neurons across Layers of Adult Human Neocortex , 2015, Cerebral cortex.

[30]  N. Logothetis,et al.  Scaling Brain Size, Keeping Timing: Evolutionary Preservation of Brain Rhythms , 2013, Neuron.

[31]  C. D. de Kock,et al.  Mechanisms Underlying the Rules for Associative Plasticity at Adult Human Neocortical Synapses , 2013, The Journal of Neuroscience.

[32]  Márton Rózsa,et al.  Fluoxetine (Prozac) and Serotonin Act on Excitatory Synaptic Transmission to Suppress Single Layer 2/3 Pyramidal Neuron-Triggered Cell Assemblies in the Human Prefrontal Cortex , 2012, The Journal of Neuroscience.

[33]  D. Kullmann,et al.  Plasticity of Inhibition , 2012, Neuron.

[34]  D. Feldman.  The Spike-Timing Dependence of Plasticity , 2012, Neuron.

[35]  W. Gerstner,et al.  Spike-Timing-Dependent Plasticity: A Comprehensive Overview , 2012, Front. Syn. Neurosci..

[36]  G. Buzsáki,et al.  Mechanisms of gamma oscillations. , 2012, Annual review of neuroscience.

[37]  Suzana Herculano-Houzel,et al.  Not All Brains Are Made the Same: New Views on Brain Scaling in Evolution , 2011, Brain, Behavior and Evolution.

[38]  Javier DeFelipe,et al.  The Evolution of the Brain, the Human Nature of Cortical Circuits, and Intellectual Creativity , 2011, Front. Neuroanat..

[39]  Alexander Borst,et al.  One Rule to Grow Them All: A General Theory of Neuronal Branching and Its Practical Application , 2010, PLoS Comput. Biol..

[40]  P. Jonas,et al.  Dendritic Mechanisms Underlying Rapid Synaptic Activation of Fast-Spiking Hippocampal Interneurons , 2010, Science.

[41]  Y. Dan,et al.  Spike timing-dependent plasticity: a Hebbian learning rule. , 2008, Annual review of neuroscience.

[42]  Lu-Yang Wang,et al.  Activity‐dependent changes in temporal components of neurotransmission at the juvenile mouse calyx of Held synapse , 2007, The Journal of physiology.

[43]  John D. Hunter,et al.  Matplotlib: A 2D Graphics Environment , 2007, Computing in Science & Engineering.

[44]  Javier DeFelipe,et al.  Double bouquet cell in the human cerebral cortex and a comparison with other mammals , 2005, The Journal of comparative neurology.

[45]  M. London,et al.  Dendritic computation. , 2005, Annual review of neuroscience.

[46]  Y. Dan,et al.  Spike Timing-Dependent Plasticity of Neural Circuits , 2004, Neuron.

[47]  M. Bear,et al.  LTP and LTD An Embarrassment of Riches , 2004, Neuron.

[48]  L. M. Ward,et al.  Synchronous neural oscillations and cognitive processes , 2003, Trends in Cognitive Sciences.

[49]  Terrence J Sejnowski,et al.  Communication in Neuronal Networks , 2003, Science.

[50]  M. Häusser,et al.  Propagation of action potentials in dendrites depends on dendritic morphology. , 2001, Journal of neurophysiology.

[51]  S. Wang,et al.  Coincidence detection in single dendritic spines mediated by calcium release , 2000, Nature Neuroscience.

[52]  D. Chklovskii,et al.  Optimal sizes of dendritic and axonal arbors in a topographic projection. , 1999, Journal of neurophysiology.

[53]  J. Csicsvari,et al.  Replay and Time Compression of Recurring Spike Sequences in the Hippocampus , 1999, The Journal of Neuroscience.

[54]  G. Bi,et al.  Synaptic Modifications in Cultured Hippocampal Neurons: Dependence on Spike Timing, Synaptic Strength, and Postsynaptic Cell Type , 1998, The Journal of Neuroscience.

[55]  J. Rinzel,et al.  The role of dendrites in auditory coincidence detection , 1998, Nature.

[56]  James H. Brown,et al.  A General Model for the Origin of Allometric Scaling Laws in Biology , 1997, Science.

[57]  D. Johnston,et al.  Regulation of Synaptic Efficacy by Coincidence of Postsynaptic APs and EPSPs , 1997 .

[58]  B. McNaughton,et al.  Replay of Neuronal Firing Sequences in Rat Hippocampus During Sleep Following Spatial Experience , 1996, Science.

[59]  B. McNaughton,et al.  Reactivation of hippocampal ensemble memories during sleep. , 1994, Science.

[60]  B. Sakmann,et al.  Active propagation of somatic action potentials into neocortical pyramidal cell dendrites , 1994, Nature.

[61]  I Segev,et al.  Signal delay and input synchronization in passive dendritic structures. , 1993, Journal of neurophysiology.

[62]  E. Capaldi,et al.  The organization of behavior. , 1992, Journal of applied behavior analysis.

[63]  C. Koch,et al.  Effect of geometrical irregularities on propagation delay in axonal trees. , 1991, Biophysical journal.

[64]  Idan Segev,et al.  Compartmental models of complex neurons , 1989 .

[65]  J. Jack,et al.  Electric current flow in excitable cells , 1975 .