Automated point-neuron simplification of data-driven microcircuit models

A method is presented for the reduction of morphologically detailed microcircuit models to a point-neuron representation without human intervention. The simplification occurs in a modular workflow, in the neighborhood of a user specified network activity state for the reference model, the "operating point". First, synapses are moved to the soma, correcting for dendritic filtering by low-pass filtering the delivered synaptic current. Filter parameters are computed numerically and independently for inhibitory and excitatory input using a Green's function approach. Next, point-neuron models for each neuron in the microcircuit are fit to their respective morphologically detailed counterparts. Here, generalized integrate-and-fire point neuron models are used, leveraging a recently published fitting toolbox. The fits are constrained by currents and voltages computed in the morphologically detailed partner neurons with soma corrected synapses at three depolarizations about the user specified operating point. The result is a simplified circuit which is well constrained by the reference circuit, and can be continuously updated as the latter iteratively integrates new data. The modularity of the approach makes it applicable also for other point-neuron and synapse models. The approach is demonstrated on a recently reported reconstruction of a neocortical microcircuit around an in vivo-like working point. The resulting simplified network model is benchmarked to the reference morphologically detailed microcircuit model for a range of simulated network protocols. The simplified network is found to be slightly more sub-critical than the reference, with otherwise good agreement for both quantitative and qualitative validations.

[1]  Steve B. Furber,et al.  A General-Purpose Model Translation System for a Universal Neural Chip , 2010, ICONIP.

[2]  Henry Markram,et al.  Fading memory and kernel properties of generic cortical microcircuit models , 2004, Journal of Physiology-Paris.

[3]  A. Polsky,et al.  Properties of basal dendrites of layer 5 pyramidal neurons: a direct patch-clamp recording study , 2007, Nature Neuroscience.

[4]  Abdesselam Bouzerdoum,et al.  Neural Information Processing. Theory and Algorithms , 2010, Lecture Notes in Computer Science.

[5]  Y. Ben‐Ari,et al.  Hippocampal CA1 lacunosum-moleculare interneurons: modulation of monosynaptic GABAergic IPSCs by presynaptic GABAB receptors. , 1995, Journal of neurophysiology.

[6]  H. Markram,et al.  Differential signaling via the same axon of neocortical pyramidal neurons. , 1998, Proceedings of the National Academy of Sciences of the United States of America.

[7]  Simon J. Thorpe,et al.  Ultra-Rapid Scene Categorization with a Wave of Spikes , 2002, Biologically Motivated Computer Vision.

[8]  M. Häusser,et al.  Estimating the Time Course of the Excitatory Synaptic Conductance in Neocortical Pyramidal Cells Using a Novel Voltage Jump Method , 1997, The Journal of Neuroscience.

[9]  Christof Koch,et al.  Biophysics of Computation: Information Processing in Single Neurons (Computational Neuroscience Series) , 1998 .

[10]  Chuandong Li,et al.  Neural Information Processing , 2012, Lecture Notes in Computer Science.

[11]  Romain Brette,et al.  Neuroinformatics Original Research Article Brian: a Simulator for Spiking Neural Networks in Python , 2022 .

[12]  M. Larkum,et al.  High I(h) channel density in the distal apical dendrite of layer V pyramidal cells increases bidirectional attenuation of EPSPs. , 2001, Journal of neurophysiology.

[13]  H. Markram,et al.  The neural code between neocortical pyramidal neurons depends on neurotransmitter release probability. , 1997, Proceedings of the National Academy of Sciences of the United States of America.

[14]  Trevor Bekolay,et al.  A Large-Scale Model of the Functioning Brain , 2012, Science.

[15]  Benjamin Torben-Nielsen,et al.  The Green’s function formalism as a bridge between single- and multi-compartmental modeling , 2013, Biological Cybernetics.

[16]  Xiao-Jing Wang,et al.  Mean-Field Theory of Irregularly Spiking Neuronal Populations and Working Memory in Recurrent Cortical Networks , 2003 .

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

[18]  Marc-Oliver Gewaltig,et al.  A Sparse Reformulation of the Green’s Function Formalism Allows Efficient Simulations of Morphological Neuron Models , 2015, Neural Computation.

[19]  I. Módy,et al.  Endogenous GABA activates small-conductance K+ channels underlying slow IPSCs in rat hippocampal neurons. , 1997, Journal of neurophysiology.

[20]  W. Rall Distinguishing theoretical synaptic potentials computed for different soma-dendritic distributions of synaptic input. , 1967, Journal of neurophysiology.

[21]  Pierre Yger,et al.  PyNN: A Common Interface for Neuronal Network Simulators , 2008, Front. Neuroinform..

[22]  Jyh-Jang Sun,et al.  Laminar and Columnar Structure of Sensory-Evoked Multineuronal Spike Sequences in Adult Rat Barrel Cortex In Vivo. , 2015, Cerebral cortex.

[23]  James G. King,et al.  Intrinsic morphological diversity of thick‐tufted layer 5 pyramidal neurons ensures robust and invariant properties of in silico synaptic connections , 2012, The Journal of physiology.

[24]  G. Stuart,et al.  Dependence of EPSP Efficacy on Synapse Location in Neocortical Pyramidal Neurons , 2002, Science.

[25]  C. Eliasmith,et al.  The use and abuse of large-scale brain models , 2014, Current Opinion in Neurobiology.

[26]  D. Turner,et al.  GABAB-Receptor-mediated currents in interneurons of the dentate-hilus border. , 1999, Journal of neurophysiology.

[27]  Thomas Nowotny,et al.  GeNN: a code generation framework for accelerated brain simulations , 2016, Scientific Reports.

[28]  D. Anderson,et al.  Algorithms for minimization without derivatives , 1974 .

[29]  A. Destexhe,et al.  The high-conductance state of neocortical neurons in vivo , 2003, Nature Reviews Neuroscience.

[30]  Addolorata Marasco,et al.  Using Strahler's analysis to reduce up to 200-fold the run time of realistic neuron models , 2013, Scientific Reports.

[31]  A. Semlyen,et al.  Rational approximation of frequency domain responses by vector fitting , 1999 .

[32]  Johannes Schemmel,et al.  A comprehensive workflow for general-purpose neural modeling with highly configurable neuromorphic hardware systems , 2010, Biological Cybernetics.

[33]  Vivien A. Casagrande,et al.  Biophysics of Computation: Information Processing in Single Neurons , 1999 .

[34]  Everton J. Agnes,et al.  Diverse synaptic plasticity mechanisms orchestrated to form and retrieve memories in spiking neural networks , 2015, Nature Communications.

[35]  Addolorata Marasco,et al.  Fast and accurate low-dimensional reduction of biophysically detailed neuron models , 2012, Scientific Reports.

[36]  Terrence C. Stewart,et al.  Neuroinformatics Original Research Article Python Scripting in the Nengo Simulator , 2022 .

[37]  G. Buzsáki,et al.  Sequential structure of neocortical spontaneous activity in vivo , 2007, Proceedings of the National Academy of Sciences.

[38]  Yaroslav O. Halchenko,et al.  Neuroscience Runs on GNU/Linux , 2011, Front. Neuroinform..

[39]  Murray Shanahan,et al.  Accelerated simulation of spiking neural networks using GPUs , 2010, The 2010 International Joint Conference on Neural Networks (IJCNN).

[40]  James G. King,et al.  Reconstruction and Simulation of Neocortical Microcircuitry , 2015, Cell.

[41]  Johannes Schemmel,et al.  Spike-Frequency Adapting Neural Ensembles: Beyond Mean Adaptation and Renewal Theories , 2007, Neural Computation.

[42]  Nikil D. Dutt,et al.  A configurable simulation environment for the efficient simulation of large-scale spiking neural networks on graphics processors , 2009, Neural Networks.

[43]  Wulfram Gerstner,et al.  Generalized integrate-and-fire models of neuronal activity approximate spike trains of a detailed model to a high degree of accuracy. , 2004, Journal of neurophysiology.

[44]  Ronald N. Bracewell,et al.  The Fourier Transform and Its Applications , 1966 .

[45]  CE Jahr,et al.  A quantitative description of NMDA receptor-channel kinetic behavior , 1990, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[46]  Wulfram Gerstner,et al.  Automated High-Throughput Characterization of Single Neurons by Means of Simplified Spiking Models , 2015, PLoS Comput. Biol..

[47]  Nicholas T. Carnevale,et al.  The NEURON Simulation Environment , 1997, Neural Computation.

[48]  Heinrich H. Bülthoff,et al.  Biologically motivated computer vision : Second International Workshop, BMCV 2002, Tübingen, Germany, November 22-24, 2002 : proceedings , 2002 .

[49]  Marc-Oliver Gewaltig,et al.  NEST (NEural Simulation Tool) , 2007, Scholarpedia.

[50]  Johannes Schemmel,et al.  Neuroinformatics Original Research Article Establishing a Novel Modeling Tool: a Python-based Interface for a Neuromorphic Hardware System , 2022 .

[51]  H. Markram,et al.  Organizing principles for a diversity of GABAergic interneurons and synapses in the neocortex. , 2000, Science.

[52]  Henry Markram,et al.  Coding of temporal information by activity-dependent synapses. , 2002, Journal of neurophysiology.